Related | Treatment Improvement Protocol (TIP) 63: Medications for Opioid Use Disorder
UPDATED 2021
Medications for Opioid Use Disorder
For Healthcare and Addiction Professionals, Policymakers, Patients, and Families
TREATMENT IMPROVEMENT PROTOCOL
TIP 63
Please share your thoughts about this publication by completing a brief online survey at:
https://www.surveymonkey.com/r/KAPPFS
The survey takes about 7 minutes to complete and is anonymous.
Your feedback will help SAMHSA develop future products.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Treatment Improvement Protocol 63
For Healthcare and Addiction Professionals, Policymakers, Patients, and Families
This TIP reviews three Food and Drug Administration-approved medications for opioid use
disorder treatment—methadone, naltrexone, and buprenorphine—and the other strategies and
services needed to support people in recovery.
TIP Navigation
Executive Summary
For healthcare and addiction professionals, policymakers, patients, and families
Part 1: Introduction to Medications for Opioid Use Disorder Treatment
For healthcare and addiction professionals, policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications for Opioid Use Disorder
For healthcare and addiction professionals, policymakers, patients, and families
ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER
PART 1: INTRODUCTION TO MEDICATIONS FOR OPIOID USE DISORDER
TREATMENT
Contents
EXECUTIVE SUMMARY
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii
TIP 63 Update . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1
Overall Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1
Content Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-3
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-7
TIP Development Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9
Publication Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-12
The Approach to OUD Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1
Overview of Medications for OUD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3
Duration of Treatment With OUD Medication. . . . . . . . . . . . . . . . . . . . . . . . . . . 1-8
Treatment Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-9
Challenges to Expanding Access to OUD Medication. . . . . . . . . . . . . . . . . . . 1-10
Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-10
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-11
PART 2: ADDRESSING OPIOID USE DISORDER IN GENERAL MEDICAL
SETTINGS
Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1
Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8
Treatment Planning or Referral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17
Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-39
iii
MEDICATIONS FOR OPIOID USE DISORDER TIP 63
PART 3: MEDICATIONS FOR OPIOID USE DISORDER
Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-1
Chapter 3A: Overview of Medications for Opioid Use Disorder . . . . . . . . . 3-5
Chapter 3B: Methadone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-17
Chapter 3C: Naltrexone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-37
Chapter 3D: Buprenorphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-51
Chapter 3E: Medical Management Strategies for Patients
Taking OUD Medications in Ofce-Based Settings. . . . . . . . . . . . . . . . . . . . . . 3-83
Chapter 3F: Medical Management of Patients Taking OUD
Medications in Hospital Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-103
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-109
PART 4: BRINGING TOGETHER ADDICTION TREATMENT COUNSELORS,
CLIENTS, AND HEALTHCARE PROFESSIONALS
Overview and Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-1
Quick Guide to Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-12
Counselor–Prescriber Communications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-18
Creation of a Supportive Counseling Experience . . . . . . . . . . . . . . . . . . . . . . . 4-20
Other Common Counseling Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-34
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-37
PART 5: RESOURCES RELATED TO MEDICATIONS FOR OPIOID USE DISORDER
General Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1
Resources for Counselors and Peer Providers . . . . . . . . . . . . . . . . . . . . . . . . . . 5-10
Resources for Clients and Families . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-12
Provider Tools and Sample Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-16
Glossary of TIP Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-56
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-59
This page intentionally left blank.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Executive Summary
For Healthcare and Addiction Professionals, Policymakers, Patients, and Families
The Executive Summary of this Treatment Improvement Protocol provides an overview on the
use of the three Food and Drug Administration-approved medications used to treat opioid use
disorder—methadone, naltrexone, and buprenorphine—and the other strategies and services
needed to support recovery.
TIP Navigation
Executive Summary
For healthcare and addiction professionals, policymakers, patients, and families
Part 1: Introduction to Medications for Opioid Use Disorder Treatment
For healthcare and addiction professionals, policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications for Opioid Use Disorder
For healthcare and addiction professionals, policymakers, patients, and families
ES-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Executive Summary
Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii
TIP 63 Update . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1
Overall Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1
Content Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-3
Part 1: Introduction to Medications for Opioid Use Disorder Treatment . . . . . . . . . . . . . ES-3
Part 2: Addressing Opioid Use Disorder in General Medical Settings . . . . . . . . . . . . . . . . ES-4
Part 3: Medications for Opioid Use Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-4
Part 4: Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-5
Part 5: Resources Related to Medications for Opioid Use Disorder . . . . . . . . . . . . . . . . . . ES-5
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-7
TIP Development Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9
Expert Panelists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9
Scientific Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-10
Field Reviewers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-10
Publication Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-12
ES-iii
TIP 63Executive Summary
Foreword
The Substance Abuse and Mental Health Services Administration (SAMHSA) is the U.S. Department of
Health and Human Services agency that leads public health efforts to reduce the impact of substance
abuse and mental illness on America’s communities. An important component of SAMHSA’s work is
focused on dissemination of evidence-based practices and providing training and technical assistance
to healthcare practitioners on implementation of these best practices.
The Treatment Improvement Protocol (TIP) series contributes to SAMHSA’s mission by providing
science-based, best-practice guidance to the behavioral health field. TIPs reflect careful consideration
of all relevant clinical and health services research, demonstrated experience, and implementation
requirements. Select nonfederal clinical researchers, service providers, program administrators, and
patient advocates comprising each TIP’s consensus panel discuss these factors, offering input on the
TIP’s specific topics in their areas of expertise to reach consensus on best practices. Field reviewers then
assess draft content and the TIP is finalized.
The talent, dedication, and hard work that TIP panelists and reviewers bring to this highly participatory
process have helped bridge the gap between the promise of research and the needs of practicing
clinicians and administrators to serve, in the most scientifically sound and effective ways, people in need
of care and treatment of mental and substance use disorders.
U.S. Department of Health and Human Services
Substance Abuse and Mental Health Services Administration
TIP 63 Update
As a reflection of SAMHSA’s commitment to ensuring that people with substance use disorders
receive timely, relevant, high-quality care, SAMHSA in May 2021 revised certain areas of all five parts
of this TIP to bring the content up to date and make it as useful to readers as possible. These changes
will help provide readers with the latest information needed to understand medications for opioid use
disorder. These changes include the following:
• Updating statistics from SAMHSA, the Centers for Disease Control and Prevention, and other
health authorities on opioid-related deaths, overdoses, accidents, and hospitalizations.
• Updating the qualifications of practitioners who are eligible to apply for a waiver to prescribe
buprenorphine (i.e., clinical nurse specialists, certified registered nurse anesthetists, and certified
nurse midwives) to include exceptions under the latest buprenorphine practice guidelines on
obtaining a waiver.
• Where needed, clarifying whether references to naltrexone refer to the oral formulation or the
extended-release injectable formulation.
• Adding recent citations that support induction onto extended-release naltrexone of people with
positive urine tests for opioids so long as they pass the naloxone challenge.
• Clarifying that naltrexone can result in decreased opioid cravings.
• Removing or replacing broken hyperlinks to online resources.
This page intentionally left blank.
ES-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Executive Summary
The goal of treatment for opioid addiction or opioid use disorder (OUD) is remission of the
disorder leading to lasting recovery. Recovery is a process of change through which individ-
uals improve their health and wellness, live self-directed lives, and strive to reach their full
potential.1 This Treatment Improvement Protocol (TIP) reviews the use of the three Food
and Drug Administration (FDA)-approved medications used to treat OUD—methadone,
naltrexone, and buprenorphine—and the other strategies and services needed to support
recovery for people with OUD.
Introduction
Our nation faces a crisis of overdose deaths from
opioids, including heroin, illicit fentanyl, and
prescription opioids. These deaths represent a
mere fraction of the total number of Americans
harmed by opioid misuse and addiction. Many
Americans now suffer daily from a chronic
medical illness called “opioid addiction” or
OUD (see the Glossary in Part 5 of this TIP for
definitions). Healthcare professionals, treatment
providers, and policymakers have a responsibility
to expand access to evidence-based, effective
care for people with OUD.
Estimated cost
of the OPIOID
EPIDEMIC was
$504
B I L L I O N
in 2015.2
An expert panel developed the TIP’s content
based on a review of the literature and on their
extensive experience in the field of addiction
treatment. Other professionals also generously
contributed their time and commitment to this
project.
An estimated 1.4M
AMERICANS
have OUD related to
opioid painkillers;
438K have heroin-
related OUD.3
The TIP is divided into parts so that readers can
easily find the material they need. Part 1 is a
general introduction to providing medications
for OUD and issues related to providing that
treatment. Some readers may prefer to go directly
to those parts most relevant to their areas of
interest, but everyone is encouraged to read
Part 1 to establish a shared understanding of
key facts and issues covered in detail in this TIP.
Following is a summary of the TIP’s overall main
points and brief summaries of each of the five
TIP parts.
Overall Key Messages
Addiction is a chronic, treatable illness.
Opioid addiction, which generally corresponds
with moderate to severe forms of OUD, often
requires continuing care for effective treatment
rather than an episodic, acute-care treatment
approach.
ES-2
Medications for Opioid Use Disorder TIP 63
Opioid overdose caused
49,860 DEATHS
nationwide in 2019—
this exceeded the #
caused by motor vehicle
crashes.4,5
General principles of good care for chronic
diseases can guide OUD treatment.
Approaching OUD as a chronic illness can
help providers deliver care that helps patients
stabilize, achieve remission of symptoms, and
establish and maintain recovery.
Patient-centered care empowers patients
with information that helps them make better
treatment decisions with the healthcare
professionals involved in their care. Patients
should receive information from their healthcare
team that will help them understand OUD and
the options for treating it, including treatment
with FDA-approved medication.
Patients with OUD should have access to
mental health services as needed, medical
care, and addiction counseling, as well as
recovery support services, to supplement
treatment with medication.
The words you use to describe OUD and
an individual with OUD are powerful. This
TIP defines, uses, and encourages providers
to adopt terminology that will not reinforce
prejudice, negative attitudes, or discrimination.
There is no “one size fits all” approach to
OUD treatment. Many people with OUD benefit
from treatment with medication for varying
lengths of time, including lifelong treatment.
Ongoing outpatient medication treatment for
OUD is linked to better retention and outcomes
than treatment without medication. Even so,
some people stop using opioids on their own;
others recover through support groups or
specialty treatment with or without medication.
The science demonstrating the effectiveness
of medication for OUD is strong. For example,
methadone, extended-release injectable naltrex-
one (XR-NTX), and buprenorphine were each
found to be more effective in reducing illicit
opioid use than no medication in randomized
clinical trials, which are the gold standard for
demonstrating efficacy in clinical medicine.6,7,8,9,10
Methadone and buprenorphine treatment
have also been associated with reduced risk of
overdose death.11,12,13,14,15
This doesn’t mean that remission and recovery
occur only through medication. Some people
achieve remission without OUD medication, just
as some people can manage type 2 diabetes
with exercise and diet alone. But just as it is
inadvisable to deny people with diabetes the
medication they need to help manage their
illness, it is also not sound medical practice to
deny people with OUD access to FDA-approved
medications for their illness.
Medication for OUD should be successfully
integrated with outpatient and residential
treatment. Some patients may benefit from
different levels of care at different points in their
lives, such as outpatient counseling, intensive
outpatient treatment, inpatient treatment, or
long-term therapeutic communities. Patients
treated in these settings should have access to
OUD medications.
1.6 MILLION
people in the U.S.,
ages 12 and older,
had OUD involving
PRESCRIPTION
OPIOIDS, HEROIN,
or both in 2019.16
ES-3
TIP 63Executive Summary
Patients treated with medications for OUD
can benefit from individualized psychosocial
supports. These can be offered by patients’
healthcare providers in the form of medication
management and supportive counseling and/or
by other providers offering adjunctive addiction
counseling, recovery coaching, mental health
services, and other services that may be needed
by particular patients.
Expanding access to OUD medications is
an important public health strategy.17 The
gap between the number of people needing
opioid addiction treatment and the capacity to
treat them with OUD medication is substantial.
In 2012, the gap was estimated at nearly 1
million people, with about 80 percent of opioid
treatment programs (OTPs) nationally operating
at 80 percent capacity or greater.18
Improving access to treatment with OUD
medications is crucial to closing the wide
gap between treatment need and treatment
availability, given the strong evidence of
effectiveness for such treatments.19
Data indicate that medications for OUD are
cost effective and cost beneficial.20,21
Content Overview
The TIP is divided into parts to make the material
more accessible according to the reader’s interests.
Part 1: Introduction to Medications for
Opioid Use Disorder Treatment
This part lays the groundwork for understanding
treatment concepts discussed later in this TIP.
The intended audience includes:
• Healthcare professionals (physicians, nurse
practitioners, physician assistants, and, until
October 1, 2023, clinical nurse specialists,
certified registered nurse anesthetists, and
certified nurse midwives).
• Professionals who offer addiction counseling
or mental health services.
O P I O I D - R E L AT E D
EMERGENCY
DEPARTMENT
visits more than tripled
from 2005 to 2017.22,23.
• Peer support specialists.
• People needing treatment and their families.
• People in remission or recovery and their
families.
• Hospital administrators.
• Policymakers.
In Part 1, readers will learn that:
• Increasing opioid overdose deaths, illicit
opioid use, and prescription opioid misuse
constitute a public health crisis.
• OUD medications reduce illicit opioid use,
retain people in treatment, and reduce risk of
opioid overdose death better than treatment
with placebo or no medication.
• Only physicians; nurse practitioners; physician
assistants; and, until October 1, 2023, clinical
nurse specialists, certified registered nurse
anesthetists, and certified nurse midwives can
prescribe buprenorphine for OUD. They must
get a federal waiver to do so.
• Only federally certified, accredited OTPs can
dispense methadone to treat OUD. OTPs
can administer and dispense buprenorphine
without a federal waiver.
• Any prescriber can offer naltrexone.
• OUD medication can be taken on a short- or
long-term basis, including as part of medically
supervised withdrawal and as maintenance
treatment.
• Patients taking medication for OUD are
considered to be in recovery.
• Several barriers contribute to the underuse of
medication for OUD.
ES-4
Medications for Opioid Use Disorder TIP 63
EVERYONE AGES
15 TO 65 should be
tested at least ONCE
for HIV . Persons at
HIGHER RISK, such as
people who use DRUGS
by injection, should be
tested ANNUALLY.
HIV
Hep C
Anyone who is injecting
or has ever INJECTED
DRUGS, even ONCE,
no matter how long
ago, should be TESTED
for HEPATITIS C,
r e g a r d l e s s o f t h e i r
i n t e n t i o n t o s e e k
TREATMENT for SUD.24,25
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
This part offers guidance on OUD screening,
assessment, treatment, and referral. Part 2 is
for healthcare professionals working in general
medical settings with patients who have or are
at risk for OUD.
In Part 2, readers will learn that:
• All healthcare practices should screen for
alcohol, tobacco, and other substance misuse
(including opioid misuse).
• Validated screening tools, symptom surveys,
and other resources are readily available; this
part lists many of them.
• When patients screen positive for risk of harm
from substance use, practitioners should
assess them using tools that determine
whether substance use meets diagnostic
criteria for a substance use disorder (SUD).
• Thorough assessment should address
patients’ medical, social, SUD, and family
histories.
• Laboratory tests can inform treatment
planning.
• Practitioners should develop treatment plans
or referral strategies (if onsite SUD treatment
is unavailable) for patients who need SUD
treatment.
Part 3: Medications for Opioid Use
Disorder
This part offers information and tools for health-
care professionals who prescribe, administer,
or dispense OUD medications or treat other
illnesses in patients who take these medications.
It provides guidance on the use of buprenorphine,
methadone, and naltrexone by healthcare
professionals in:
• General medical settings, including hospitals.
• Office-based opioid treatment settings.
• Specialty addiction treatment programs,
including OTPs.
In Part 3, readers will learn that:
• OUD medications are safe and effective when
used appropriately.
OPIOID-RELATED
inpatient hospital stays
INCREASED 119%
nationally from 2005 to 2017.26,27
ES-5
TIP 63Executive Summary
• OUD medications can help patients reduce or
stop illicit opioid use and improve their health
and functioning.
• Medications should be considered for all
patients with OUD. Opioid medications
should be reserved for those with moderate-
to-severe OUD with physical dependence.
• Patients with OUD should be informed of
the risks and benefits of medications to treat
OUD, treatment without medication, and no
treatment.
• Patients should be advised on where and
how to get treatment with OUD medication.
• Doses and schedules of medications must be
individualized.
Part 4: Bringing Together Addiction
Treatment Counselors, Clients, and
Healthcare Professionals
This part recommends ways that addiction
treatment counselors can collaborate with
healthcare professionals to support client-
centered, trauma-informed OUD treatment
and recovery. It also serves as a quick guide to
medications that can treat OUD and presents
strategies for clear communication with pre-
scribers, creation of supportive environments
for clients who take OUD medication, and ways
to address other common counseling concerns
when working with this population.
In Part 4, readers will learn that:
• Many patients taking OUD medication benefit
from counseling as part of treatment.
• Counselors play the same role for clients with
OUD who take medication as for clients with
any other SUD.
• Counselors help clients recover by addressing
the challenges and consequences of addiction.
• OUD is often a chronic illness requiring
ongoing communication among patients and
providers to ensure that patients fully benefit
from both medication and psychosocial
treatment and support.
OPIOID ADDICTION
is linked with high rates of
ILLEGAL ACTIVITY and
INCARCERATION.28,29
• OUD medications are safe and effective when
prescribed and taken appropriately.
• Medication is integral to recovery for many
people with OUD. Medication usually
produces better treatment outcomes than
outpatient treatment without medication.
• Supportive counseling environments for
clients who take OUD medication can
promote treatment and help build recovery
capital.
Part 5: Resources Related to Medications
for Opioid Use Disorder
This part has a glossary and audience-segmented
resource lists to help medical and behavioral
health service providers better understand how
to use OUD medications with their patients and
to help patients better understand how OUD
medications work. It is for all interested readers.
In Part 5, readers will learn that:
• Practice guidelines and decision-making tools
can help healthcare professionals with OUD
screening, assessment, diagnosis, treatment
planning, and referral.
• Patient- and family-oriented resources provide
information about opioid addiction in general;
the role of medication, behavioral and sup-
portive services, and mutual-help groups in
the treatment of OUD; how-tos for identifying
recovery support services; and how-tos for
locating medical and behavioral health service
providers who specialize in treating OUD or
other SUDs.
ES-6
Medications for Opioid Use Disorder TIP 63
PRESCRIBING
CONSIDERATIONS METHADONE NALTREXONE BUPRENORPHINE
Mechanism of
Action at mu-
Opioid Receptor
Agonist Antagonist Partial agonist
Phase of
Treatment
Medically
supervised
withdrawal,
maintenance
Prevention of relapse to
opioid misuse, following
medically supervised
withdrawal
Medically supervised withdrawal,
maintenance
Route of
Administration
Oral Oral, intramuscular
extended-release
Sublingual, buccal, subdermal
implant, subcutaneous extended
release injection
Possible Adverse
Effects
Constipation,
hyperhidrosis,
respiratory
depression,
sedation, QT
prolongation,
sexual dysfunction,
severe hypotension
including
orthostatic
hypotension and
syncope, misuse
potential, neonatal
abstinence
syndrome
Nausea, anxiety,
insomnia, precipitated
opioid withdrawal,
hepatotoxicity,
vulnerability to opioid
overdose, depression,
suicidality, muscle
cramps, dizziness or
syncope, somnolence
or sedation, anorexia,
decreased appetite or
other appetite disorders
Intramuscular: Pain,
swelling, induration
(including some cases
requiring surgical
intervention)
Constipation, nausea,
precipitated opioid withdrawal,
excessive sweating, insomnia,
pain, peripheral edema,
respiratory depression
(particularly combined with
benzodiazepines or other CNS
depressants), misuse potential,
neonatal abstinence syndrome
Implant: Nerve damage during
insertion/removal, accidental
overdose or misuse if extruded,
local migration or protrusion
Subcutaneous Injection:
Injection site itching or pain,
death from intravenous injection
Regulations and
Availability
Schedule II; only
available at federally
certified OTPs and
the acute inpatient
hospital setting for
OUD treatment
Not a scheduled
medication; not included
in OTP regulations;
requires prescription;
office-based treatment
or specialty substance
use treatment programs,
including OTPs
Schedule III; requires waiver to
prescribe outside OTPs
Implant: Prescribers must be
certified in the Probuphine
Risk Evaluation and Mitigation
Strategy (REMS) Program.
Providers who wish to insert/
remove implants are required
to obtain special training
and certification in the REMS
Program
Subcutaneous Injection:
Healthcare settings and
pharmacies must be certified
in the Sublocade REMS
Program and only dispense the
medication directly to a provider
for administration
Adapted with permission.30 Copyrighted 2017. UBM Medica. 131265:0917SH
EXHIBIT ES.1. Comparison of Medications for OUD
ES-7
TIP 63Executive Summary
Notes
1 Substance Abuse and Mental Health Services
Administration. (2017). Recovery and recovery support
[Webpage]. Retrieved November 17, 2017, from
www.samhsa.gov/recovery
2 Council of Economic Advisers. (2017, November). The
underestimated cost of the opioid crisis. Washington, DC:
Executive Office of the President of the United States.
3 Center for Behavioral Health Statistics and Quality. (2020).
Results from the 2019 National Survey on Drug Use and
Health: Detailed tables. Rockville, MD: Substance Abuse
and Mental Health Services Administration. Retrieved
May 21, 2021, from www.samhsa.gov/data/
4 Centers for Disease Control and Prevention, National
Center for Health Statistics. (2020). Multiple Cause of
Death 2018-2019 on CDC WONDER Online Database,
released in 2020. Retrieved April 29, 2021, from http://
wonder.cdc.gov/mcd-icd10.html
5 National Highway Traffic Safety Administration. (2020).
NHTSA Releases 2019 Crash Fatality Data. Retrieved
April 29, 2021, from www.nhtsa.gov/press-releases/
nhtsa-releases-2019-crash-fatality-data
6 Johnson, R. E., Chutuape, M. A., Strain, E. C., Walsh, S.
L., Stitzer, M. L., & Bigelow, G. E. (2000). A comparison
of levomethadyl acetate, buprenorphine, and methadone
for opioid dependence. New England Journal of
Medicine, 343(18), 1290–1297.
7 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011, April 30).
Injectable extended-release naltrexone for opioid
dependence: A double-blind, placebo-controlled,
multicentre randomised trial. Lancet, 377(9776),
1506–1513.
8 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
9 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
10 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
11 Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède,
J. P., & Tignol, J. (2004). French field experience with
buprenorphine. American Journal on Addictions,
13(Suppl. 1), S17–S28.
12 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
13 Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
14 Schwartz, R. P., Gryczynski, J., O’Grady, K. E., Sharfstein,
J. M., Warren, G., Olsen, Y., … Jaffe, J. H. (2013). Opioid
agonist treatments and heroin overdose deaths in
Baltimore, Maryland, 1995–2009. American Journal of
Public Health, 103(5), 917–922.
15 World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment of
opioid dependence. Geneva, Switzerland: WHO Press.
16 Center for Behavioral Health Statistics and Quality. (2020).
Results from the 2019 National Survey on Drug Use and
Health: Detailed tables. Rockville, MD: Substance Abuse
and Mental Health Services Administration. Retrieved
May 21, 2021, from www.samhsa.gov/data/
17 Department of Health and Human Services, Office of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
18 Jones, C. M., Campopiano, M., Baldwin, G., & McCance-
Katz, E. (2015). National and state treatment need
and capacity for opioid agonist medication-assisted
treatment. American Journal of Public Health, 105(8),
e55–e63.
19 Jones, C. M., Campopiano, M., Baldwin, G., & McCance-
Katz, E. (2015). National and state treatment need
and capacity for opioid agonist medication-assisted
treatment. American Journal of Public Health, 105(8),
e55–e63.
20 Cartwright, W. S. (2000). Cost-benefit analysis of drug
treatment services: Review of the literature. Journal of
Mental Health Policy and Economics, 3(1), 11–26.
21 McCollister, K. E., & French, M. T. (2003). The relative
contribution of outcome domains in the total economic
benefit of addiction interventions: A review of first
findings. Addiction, 98(12), 1647–1659.
22 Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A.,
Bailey, M. K., & O’Malley, L. (2017, January). Opioid-
related inpatient stays and emergency department visits
by state, 2009–2014. HCUP Statistical Brief No. 219.
Rockville, MD: Agency for Healthcare Research and
Quality.
ES-8
Medications for Opioid Use Disorder TIP 63
23 Agency for Healthcare Research and Quality. (2020).
Rate of opioid-related ED visits per 100,000 population.
Retrieved April 29, 2021, from www.hcup-us.ahrq.gov/
faststats/OpioidUseMap?setting=ED
24 U.S. Preventive Services Task Force. (2013). Archived
Final Recommendation Statement on Human
Immunodeficiency Virus (HIV) Infection: Screening.
December 30, 2013. Retrieved January 11, 2020,
from www.uspreventiveservicestaskforce.org/Page/
Document/RecommendationStatementFinal/human-
immunodeficiency-virus-hiv-infection-screening#consider
25 Centers for Disease Control and Prevention. (2015).
Testing recommendations for hepatitis C virus infection.
October 15, 2015. Retrieved January 11, 2020, from
www.cdc.gov/hepatitis/hcv/guidelinesc.htm
26 Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A.,
Bailey, M. K., & O’Malley, L. (2017, January). Opioid-
related inpatient stays and emergency department visits
by state, 2009–2014. HCUP Statistical Brief No.219.
Rockville, MD: Agency for Healthcare Research and
Quality.
27 Agency for Healthcare Research and Quality. (2020). Rate
of opioid-related inpatient stays per 100,000 population.
Retrieved April 29, 2021, from www.hcup-us.ahrq.gov/
faststats/OpioidUseMap?setting=IP
28 World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment of
opioid dependence. Geneva, Switzerland: WHO Press.
29 Soyka, M., Träder, A., Klotsche, J., Haberthür, A.,
Bühringer, G., Rehm, J., & Wittchen, H. U. (2012).
Criminal behavior in opioid-dependent patients before
and during maintenance therapy: 6-year follow-up of
a nationally representative cohort sample. Journal of
Forensic Sciences, 57(6), 1524–1530.
30 Brezing, C., & Bisaga, A. (2015, April 30). Opioid use
disorder: Update on diagnosis and treatment. Psychiatric
Times, 32(4) 1–4.
ES-9
TIP 63Executive Summary
TIP Development Participants
Expert Panelists
Each Treatment Improvement Protocol’s (TIP’s) expert panel is a group of primarily nonfederal
addiction-focused clinical, research, administrative, and recovery support experts with deep
knowledge of the TIP’s topic. With the Substance Abuse and Mental Health Services Administration’s
(SAMHSA’s) Knowledge Application Program (KAP) team, they develop each TIP via a consensus-
driven, collaborative process that blends evidence-based, best, and promising practices with the
panel’s expertise and combined wealth of experience. (Note that affiliations reflect those relevant
at the time of the individual’s review.)
TIP Chair
Robert P. Schwartz, M.D.—TIP Chair
Medical Director/Senior Research Scientist
Friends Research Institute
Baltimore, MD
TIP Expert Panelists
Sarah Church, Ph.D.
Executive Director
Montefiore Medical Center
Wellness Center at Waters Place
Bronx, NY
Diana Coffa, M.D., FM
Associate Professor
University of California School of Medicine
Family Community Medicine
San Francisco, CA
Zwaantje Hamming, M.S.N., FNP-C, CARN-AP
La Familia Medical Center
Santa Fe, NM
Ron Jackson, M.S.W., LICSW
Affiliate Professor
University of Washington School of Social Work
Seattle, WA
Hendree Jones, Ph.D.
Professor and Executive Director
Horizons Program
Chapel Hill, NC
Michelle Lofwall, M.D., DFASAM
Medical Director
University of Kentucky College of Medicine—
Straus Clinic
Associate Professor of Behavioral Science and
Psychiatry
Faculty in UK Center on Drug and Alcohol
Research
Lexington, KY
Shannon C. Miller, M.D., DFASAM, DFAPA
(ad hoc panelist)
Director, Addiction Services
Veterans Affairs Medical Center
Cincinnati, OH
Charles Schauberger, M.D.
Obstetrician-Gynecologist
Gundersen Health System
La Crosse, WI
Joycelyn Woods, M.A., CMA
Executive Director
National Alliance for Medication Assisted
Recovery
New York, NY
SAMHSA’s TIP Champion
Melinda Campopiano von Klimo, M.D.
Senior Medical Advisor
Center for Substance Abuse Treatment
SAMHSA
Rockville, MD
ES-10
Medications for Opioid Use Disorder TIP 63
Scientific Reviewers
This TIP’s scientific reviewers are among the foremost experts on the three medications discussed in
this TIP to treat opioid use disorder. Their role in the collaborative TIP development process was to
help the KAP team include current, accurate, and comprehensive information and instructions about
the use of each of these medications. (Note that affiliations reflect those relevant at the time of the
individual’s review.)
Buprenorphine
David A. Fiellin, M.D.
Professor of Investigative Medicine and Public
Health
Yale University School of Medicine
New Haven, CT
Methadone
Andrew J. Saxon, M.D.
Professor
Department of Psychiatry and Behavioral
Sciences
University of Washington School of Medicine
Director
Center of Excellence in Substance Abuse
Treatment and Education
Veterans Affairs Puget Sound Health Care System
Seattle, WA
Naltrexone
Joshua D. Lee, M.D., M.Sc.
Associate Professor
Department of Population Health
Division of General Medicine and Clinical
Innovation
NYU Langone Health
New York, NY
Field Reviewers
Field reviewers represent each TIP’s intended target audiences. They work in addiction, mental health,
primary care, and adjacent fields. Their direct front-line experience related to the TIP’s topic allows
them to provide valuable input on a TIP’s relevance, utility, accuracy, and accessibility. (Note that
affiliations reflect those relevant at the time of the individual’s review.)
William Bograkos, M.A., D.O., FACOEP,
FACOFP
Adjunct Professor
Center for Excellence in the Neurosciences
University of New England (UNE)
Clinical Professor of Medical Military Science
Family Practice and Emergency Medicine, UNE
Biddeford, ME
Meg Brunner, M.L.I.S.
Librarian, Alcohol and Drug Abuse Institute
University of Washington
Seattle, WA
Kathryn Cates-Wessell
Chief Executive Officer
American Academy of Addiction Psychiatry
East Providence, RI
Mary Catlin, BSN, M.P.H., CIC
Public Health Nurse
Alcohol and Drug Abuse Institute
University of Washington
Seattle, WA
Kelly J. Clark, M.D., M.B.A., DFASAM
President
American Society of Addiction Medicine
Rockville, MD
Marc Fishman, M.D.
Assistant Professor
Johns Hopkins University School of Medicine,
Psychiatry/Behavioral Sciences Expert Team
Baltimore, MD
Katherine Fornili, D.N.P., M.P.H., RN, CARN
Assistant Professor
University of Maryland School of Nursing
Baltimore, MD
ES-11
TIP 63Executive Summary
Adam Gordon, M.D., M.P.H., FACP, FASAM,
CMRO
Associate Professor of Medicine and Advisory
Dean
University of Pittsburgh School of Medicine
Pittsburgh, PA
Ellie Grossman, M.D.
Instructor in Medicine
Cambridge Health Alliance
Somerville Hospital Primary Care
Somerville, MA
Kyle Kampman, M.D.
Professor, Department of Psychiatry
Perelman School of Medicine
University of Pennsylvania
Center for Studies of Addiction
Philadelphia, PA
Janice Kauffman, M.P.H., RN, CAS, CADC-1
Vice President of Addiction Treatment Services,
North Charles Foundation, Inc.
Director of Addictions Consultation, Department
of Psychiatry, Cambridge Health Alliance
Assistant Professor of Psychiatry, Harvard
Medical School, the Cambridge Hospital
Cambridge, MA
Jason Kletter, Ph.D.
President, Bay Area Addiction Research and
Treatment
President, California Opioid Maintenance
Providers
San Francisco, CA
William J. Lorman, J.D., Ph.D., MSN,
PMHNP-BC, CARN-AP
Vice President and Chief Clinical Officer
Livengrin Foundation, Inc.
Bensalem, PA
Megan Marx-Varela, M.P.A.
Associate Director
The Joint Commission—Behavioral Health Care
Accreditation
Oakbrook Terrace, IL
Alison Newman, M.P.H.
Continuing Education Specialist
Alcohol and Drug Abuse Institute
University of Washington
Seattle, WA
David O’Gurek, M.D., FAAFP
Assistant Professor
Family and Community Medicine, Lewis Katz
School of Medicine
Temple University
Philadelphia, PA
Yngvild Olsen, M.D., M.P.H, FASAM
Medical Director
Institutes for Behavior Resources, Inc./Recovery
Enhanced by Access to Comprehensive
Healthcare (REACH) Health Services
Baltimore, MD
Shawn A. Ryan, M.D., M.B.A., ABEM, FASAM
President & Chief Medical Officer
BrightView
Cincinnati, OH
Paul Stasiewicz, Ph.D.
Senior Research Scientist
Research Institute on Addictions
State University of New York-Buffalo
Buffalo, NY
Kenneth Stoller, M.D.
Director
Broadway Center for Addiction at the Johns
Hopkins Hospital
Assistant Professor of Psychiatry and Behavioral
Sciences
Johns Hopkins University
Baltimore, MD
Mishka Terplan, M.D., M.P.H., FACOG
Professor
Department of Obstetrics and Gynecology,
Division of General Obstetrics and Gynecology
Virginia Commonwealth University
Richmond, VA
Christopher Welsh, M.D.
Associate Professor of Psychiatry
University of Maryland Medical Center
Baltimore, MD
George E. Woody, M.D.
Professor of Psychiatry
Department of Psychiatry Center for Studies of
Addiction
University of Pennsylvania’s Perelman School of
Medicine
Philadelphia, PA
ES-12
Medications for Opioid Use Disorder TIP 63
Publication Information
Acknowledgments
This publication was prepared under contract numbers 270-14-0445 and 283-17-4901 by the
Knowledge Application Program (KAP) for the Center for Substance Abuse Treatment, Substance
Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human
Services (HHS). Suzanne Wise served as the Contracting Officer’s Representative, and Candi Byrne
served as KAP Project Coordinator.
Disclaimer
The views, opinions, and content expressed herein are the views of the consensus panel members and
do not necessarily reflect the official position of SAMHSA or HHS. No official support of or endorse-
ment by SAMHSA or HHS for these opinions or for the instruments or resources described is intended
or should be inferred. The guidelines presented should not be considered substitutes for individual-
ized client care and treatment decisions.
Public Domain Notice
All materials appearing in this publication except those taken directly from copyrighted sources are
in the public domain and may be reproduced or copied without permission from SAMHSA or the
authors. Citation of the source is appreciated. However, this publication may not be reproduced or
distributed for a fee without the specific, written authorization of the Office of Communications,
SAMHSA, HHS.
Electronic Access and Copies of Publication
This publication may be ordered or downloaded from SAMHSA’s Publications Ordering webpage at
https://store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English
and Español).
Recommended Citation
Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder.
Treatment Improvement Protocol (TIP) Series 63 Publication No. PEP21-02-01-002. Rockville, MD:
Substance Abuse and Mental Health Services Administration, 2021.
Originating Office
Quality Improvement and Workforce Development Branch, Division of Services Improvement, Center
for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 5600
Fishers Lane, Rockville, MD 20857.
Nondiscrimination Notice
SAMHSA complies with applicable federal civil rights laws and does not discriminate on the basis of
race, color, national origin, age, disability, or sex. SAMHSA cumple con las leyes federales de derechos
civiles aplicables y no discrimina por motivos de raza, color, nacionalidad, edad, discapacidad, o sexo.
Publication No. PEP21-02-01-002
First released 2018. Revised 2019, 2020, and 2021.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Part 1: Introduction to Medications for Opioid Use Disorder Treatment
For Healthcare and Addiction Professionals, Policymakers, Patients, and Families
Part 1 of this Treatment Improvement Protocol (TIP) will help readers understand key facts and
issues related to providing Food and Drug Administration (FDA)-approved medications used to
treat opioid use disorder (OUD).
TIP Navigation
Executive Summary
For healthcare and addiction professionals,
policymakers, patients, and families
Part 1: Introduction to Medications for
Opioid Use Disorder Treatment
For healthcare and addiction
professionals, policymakers,
patients, and families
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment
Counselors, Clients, and Healthcare
Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications for
Opioid Use Disorder
For healthcare and addiction professionals,
policymakers, patients, and families
KEY MESSAGES
• Increasing opioid overdose deaths, illicit
opioid use, and prescription opioid misuse
constitute a public health crisis.
• OUD medications reduce illicit opioid use,
retain people in treatment, and reduce
risk of opioid overdose death better than
treatment with placebo or no medication.
• Only physicians; nurse practitioners;
physician assistants; and, until October 1,
2023, clinical nurse specialists, certifed
registered nurse anesthetists, and
certifed nurse midwives can prescribe
buprenorphine for OUD. They must get a
federal waiver to do so.
• Only federally certifed, accredited opioid
treatment programs (OTPs) can dispense
methadone to treat OUD. OTPs can
administer and dispense buprenorphine
without a federal waiver.
• Any prescriber can offer naltrexone.
• OUD medication can be taken on a short-
or long-term basis, including as part of
medically supervised withdrawal and as
maintenance treatment.
• Patients taking medication for OUD are
considered to be in recovery.
• Several barriers contribute to the
underuse of medication for OUD.
1-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 1 of 5
Contents
The Approach to OUD Care 1-1
Overview of Medications for OUD 1-3
Benefts 1-3
Efectiveness 1-3
Cost Efectiveness and Cost Benefts 1-7
Requirements and Regulations 1-7
Duration of Treatment With OUD Medication 1-8
Maintenance Treatment 1-8
Medication Taper 1-9
Medically Supervised Withdrawal 1-9
Treatment Settings 1-9
Challenges to Expanding Access to OUD Medication 1-10
Resources 1-10
Notes 1-11
1-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
PART 1 of 5
Introduction to Medications for Opioid Use
Disorder Treatment
Part 1 of this TIP offers a general introduction to providing medications to address opioid use
disorder (OUD). It is for all audiences. Part 1 will help readers understand key facts and issues
related to providing FDA-approved medications used to treat OUD. TIP Parts 2 through 5 cover
these issues in more detail.
The Approach to OUD Care
According to the Substance Abuse and Mental
Health Services Administration (SAMHSA)
and the National Institute on Drug Abuse,
addiction is a chronic, treatable illness. Opioid
addiction, which generally corresponds with
moderate to severe forms of OUD (Exhibit 1.1),
often requires continuing care for effective
treatment rather than an episodic, acute-care
treatment approach.
The World Health Organization’s (WHO’s)
principles of good care for chronic diseases
can guide OUD care:1
• Develop a treatment partnership with patients.
• Focus on patients’ concerns and priorities.
• Support patient self-management of illness.
• Use the fve A’s at every visit (assess, advise,
agree, assist, and arrange).
• Organize proactive follow-up.
• Link patients to community resources/support.
• Work as a clinical team.
• Involve “expert patients,” peer educators,
and support staff in the health facility.
• Ensure continuity of care.
Chronic care management is effective for many
long-term medical conditions, such as diabetes
and cardiovascular disease, and it can offer
Estimated cost
of the OPIOID
EPIDEMIC was
$504
B I L L I O N
in 2015.2
similar benefts to patients with substance use
disorders (SUDs); for example, it can help them
stabilize, achieve remission of symptoms, and
establish and maintain recovery. Good con-
tinuing care also provides, and links to, other
medical, behavioral health, and community and
recovery support services.
A noticeable theme in chronic disease
management is patient-centered care.
Patient-centered care empowers patients
with information that helps them make better
treatment decisions with the healthcare profes-
sionals involved in their care. Patients should
receive information from their healthcare team
that will help them understand OUD and the
options for treating it, including treatment
with FDA-approved medications. Healthcare
professionals should also make patients aware
of available, appropriate recovery support and
behavioral health services.
1-2
Medications for Opioid Use Disorder TIP 63
EXHIBIT 1.1. Key Terms
Addiction: As defned by the American Society of Addiction Medicine, “a primary, chronic disease of
brain reward, motivation, memory, and related circuitry.”3 It is characterized by inability to consistently
abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with
one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other
chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic purposes, but it
commonly describes the more severe forms of OUD.
Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an
alpha-2 adrenergic agonist if an opioid agonist is not available) in tapering doses or other medications to
help a patient discontinue illicit or prescription opioids.
Opioid misuse: The use of prescription opioids in any way other than as directed by a prescriber; the
use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5
Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity
at cell receptors in the central nervous system (CNS) that are normally stimulated by opioids. Mu-opioid
receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to
those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect.
Mu-opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full
agonists, increasing their dose may not produce additional effects once they have reached their maximal
effect. At low doses, partial agonists may produce effects similar to those of full agonists.
Opioid receptor antagonist: A substance that has affnity for opioid receptors in the CNS without
producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone)
can block the effects of exogenously administered opioids.
Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine.
They can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone).
Opioid treatment program (OTP): An accredited treatment program with SAMHSA certifcation
and Drug Enforcement Administration registration to administer and dispense opioid agonist
medications that are approved by FDA to treat opioid addiction. Currently, these include methadone and
buprenorphine products. Other pharmacotherapies, such as naltrexone, may be provided but are not
subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational,
and other assessment and treatment services either onsite or by referral to an outside agency or
practitioner through a formal agreement.6
Opioid use disorder (OUD): Per DSM-5, a disorder characterized by loss of control of opioid use,
risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do not
count toward the diagnosis in people experiencing these symptoms when using opioids under appropriate
medical supervision. OUD covers a range of severity and replaces what DSM-IV termed “opioid abuse” and
“opioid dependence.” An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2
of the 11 symptoms in a 12-month period. (See Exhibit 2.13 in Part 2 for full DSM-5 diagnostic criteria for OUD.)
Recovery: A process of change through which individuals improve their health and wellness, live self-
directed lives, and strive to reach their full potential. Even individuals with severe and chronic SUDs can,
with help, overcome their SUDs and regain health and social function. Although abstinence from all
substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature.
Patients taking FDA-approved medication to treat OUD can be considered in recovery.
Relapse: A process in which a person with OUD who has been in remission experiences a return of
symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more
than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need
not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality.
Remission: A medical term meaning a disappearance of signs and symptoms of the disease.7 DSM-5
defnes remission as present in people who previously met OUD criteria but no longer meet any OUD
criteria (with the possible exception of craving).8 Remission is an essential element of recovery.
Return to opioid use: One or more instances of opioid misuse without a return of symptoms of
OUD. A return to opioid use may lead to relapse.
1-3
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
As is true for patients undergoing treatment
for any chronic medical condition, patients
with OUD should have access to medical,
mental health, addiction counseling, and
recovery support services that they may
need to supplement treatment with medication.
Medical care should include preventive services
and disease management. Patients with OUD
who have mental disorders should have access
to mental health services.
Treatment and support services should refect
each patient’s individual needs and preferences.
Some patients, particularly those with co-
occurring disorders, may require these treatments
and services to achieve sustained remission and
recovery.
The words you use to describe both OUD and
an individual with OUD are powerful and can
reinforce prejudice, negative attitudes, and
discrimination. Negative attitudes held by the
public and healthcare professionals can deter
people from seeking treatment, make patients
leave treatment prematurely, and contribute to
worse treatment outcomes. The TIP expert panel
recommends that providers always use medical
terms when discussing SUDs (e.g., positive or
negative urine sample, not dirty or clean sample)
and use person-frst language (e.g., a person
with an SUD, not a user, alcoholic, or addict).
Exhibit 1.1 defnes some key terms. A full
glossary is in Part 5 of this TIP.
RESOURCE ALERT
Shared Decision Making
SAMHSA’s shared decision-making resource
page is helpful for educating patients and their
families about OUD. The information provided
can help patients make informed decisions
about their care (www.samhsa.gov/brss-tacs/
recovery-support-tools/shared-decision-
making).
Overview of Medications for OUD
There is no “one size fts all” approach to
OUD treatment. Many people with OUD beneft
from treatment with medication for varying
lengths of time, including lifelong treatment.
Ongoing outpatient medication treatment for
OUD is linked to better retention and outcomes
than treatment without medication. Even so,
some people stop using opioids on their own;
others recover through support groups or
specialty outpatient or residential treatment
with or without medication. Still, FDA-approved
medication should be considered and offered to
patients with OUD as part of their treatment.
Benefts
The three FDA-approved medications used
to treat OUD improve patients’ health and
wellness by:
• Reducing or eliminating withdrawal
symptoms: methadone, buprenorphine.
• Blunting or blocking the effects of
illicit opioids: methadone, naltrexone,
buprenorphine.
• Reducing or eliminating cravings to
use opioids: methadone, naltrexone,
buprenorphine.
See Exhibit 1.2 for further comparison between
these medications.
Efectiveness
The science demonstrating the effectiveness
of medication for OUD is strong. For example,
methadone, extended-release injectable naltrex-
one (XR-NTX), and buprenorphine were each
found to be more effective in reducing illicit
opioid use than no medication in randomized
clinical trials,9,10,11,12 which are the gold standard
for demonstrating effcacy in clinical medicine.
Methadone and buprenorphine treatment
have also been associated with reduced risk of
overdose death.13,14,15,16,17
1-4
Medications for Opioid Use Disorder TIP 63
EXHIBIT 1.2. Comparison of Medications for OUD
PRESCRIBING
CONSIDERATIONS METHADONE NALTREXONE BUPRENORPHINE
Mechanism of
Action at mu-
Opioid Receptor
Agonist Antagonist Partial agonist
Phase of
Treatment
Medically
supervised
withdrawal,
maintenance
Prevention of relapse to
opioid misuse, following
medically supervised
withdrawal
Medically supervised withdrawal,
maintenance
Route of
Administration
Oral Oral, intramuscular
extended-release
Sublingual, buccal, subdermal
implant, subcutaneous extended
release injection
Possible Adverse
Effects
Constipation,
hyperhidrosis,
respiratory
depression,
sedation, QT
prolongation,
sexual dysfunction,
severe hypotension
including
orthostatic
hypotension and
syncope, misuse
potential, neonatal
abstinence
syndrome
Nausea, anxiety,
insomnia, precipitated
opioid withdrawal,
hepatotoxicity,
vulnerability to opioid
overdose, depression,
suicidality, muscle
cramps, dizziness or
syncope, somnolence
or sedation, anorexia,
decreased appetite or
other appetite disorders
Intramuscular: Pain,
swelling, induration
(including some cases
requiring surgical
intervention)
Constipation, nausea,
precipitated opioid withdrawal,
excessive sweating, insomnia,
pain, peripheral edema,
respiratory depression
(particularly combined with
benzodiazepines or other CNS
depressants), misuse potential,
neonatal abstinence syndrome
Implant: Nerve damage during
insertion/removal, accidental
overdose or misuse if extruded,
local migration or protrusion
Subcutaneous Injection:
Injection site itching or pain,
death from intravenous injection
Regulations and
Availability
Schedule II; only
available at federally
certifed OTPs and
the acute inpatient
hospital setting for
OUD treatment
Not a scheduled
medication; not included
in OTP regulations;
requires prescription;
offce-based treatment
or specialty substance
use treatment programs,
including OTPs
Schedule III; requires waiver to
prescribe outside OTPs
Implant: Prescribers must be
certifed in the Probuphine
Risk Evaluation and Mitigation
Strategy (REMS) Program.
Providers who wish to insert/
remove implants are required
to obtain special training
and certifcation in the REMS
Program
Subcutaneous Injection:
Healthcare settings and
pharmacies must be certifed
in the Sublocade REMS
Program and only dispense the
medication directly to a provider
for administration
Adapted with permission.18 Copyrighted 2017. UBM Medica. 131265:0917SH
1-5
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
This doesn’t mean that remission and recovery
occur only through medication. Some people
achieve remission without OUD medication, just
as some people can manage type 2 diabetes
with exercise and diet alone. But just as it is
inadvisable to deny people with diabetes the
medication they need to help manage their
illness, it is also not sound medical practice to
deny people with OUD access to FDA-approved
medications for their illness.
Medication for OUD should be successfully
integrated with outpatient and residential
treatment. Some patients may beneft from
different levels of care during the course of their
lives. These different levels include outpatient
counseling, intensive outpatient treatment,
inpatient treatment, or long-term therapeutic
communities. Patients receiving treatment in
these settings should have access to FDA-
approved medications for OUD.
Patients treated with OUD medications can
beneft from individualized psychosocial
supports. These can be offered by patients’
healthcare providers in the form of medication
management and supportive counseling and/or
by other providers offering adjunctive addiction
counseling, contingency management, recovery
coaching, mental health services, and other
services (e.g., housing supports) that particular
patients may need.
The TIP expert panel strongly
recommends informing all patients
with OUD about the risks and benefts
of treatment of OUD with all FDA-
approved medications. Alternatives
to these treatments and their risks
and benefts should be discussed.
Patients should receive access to such
medications if clinically appropriate
and desired by the patients.
Expanding access to FDA-approved medica-
tions is an important public health strategy.19
A substantial gap exists between the number of
people needing OUD treatment and the capacity
to treat those individuals with OUD medication.
In 2012, the gap was estimated at nearly 1
million people, with approximately 80 percent of
OTPs nationally operating at 80 percent capacity
or greater.20 Blue Cross Blue Shield reported a
493 percent increase in members diagnosed with
OUD from 2010 to 2016 but only a 65 percent
increase in the use of medication for OUD.21
Improving access is crucial to closing the wide
gap between the need for treatment with
OUD medications and the availability of such
treatment, given the strong evidence of OUD
medications’ effectiveness.22
Methadone
Methadone retains patients in treatment and
reduces illicit opioid use more effectively than
placebo, medically supervised withdrawal, or
no treatment, as numerous clinical trials and
meta-analyses of studies conducted in many
countries show.23,24,25 Higher methadone doses
are associated with superior outcomes.26,27 Given
the evidence of methadone’s effectiveness, WHO
lists it as an essential medication.28
Methadone treatment has by far the largest,
oldest evidence base of all treatment ap-
proaches to opioid addiction. Large multisite
longitudinal studies from the world over support
methadone maintenance’s effectiveness.29,30,31
Longitudinal studies have also found that it is
associated with:32,33,34,35,36,37,38,39,40
• Reduced risk of overdose-related deaths.
• Reduced risk of HIV and hepatitis C infection.
• Lower rates of cellulitis.
• Lower rates of HIV risk behavior.
• Reduced criminal behavior.
1-6
Medications for Opioid Use Disorder TIP 63
Naltrexone
XR-NTX reduces illicit opioid use and retains
patients in treatment more effectively than
placebo and no medication, according to
fndings from randomized controlled trials.41,42,43
In a two-group random assignment study of
adults who were opioid dependent and involved
in the justice system, all participants received
brief counseling and community treatment
referrals. One group received no medication,
and the other group received XR-NTX. During
the 6-month follow-up period, compared
with the no-medication group, the group that
received the medication demonstrated:44
• Longer time to return to substance use (10.5
weeks versus 5.0 weeks).
• A lower rate of return to use (43 percent
versus 64 percent).
• A higher percentage of negative urine screens
(74 percent versus 56 percent).
There are two studies comparing XR-NTX to
sublingual buprenorphine. A multisite random-
ized trial assigned adult residential treatment
patients with OUD to either XR-NTX or bu-
prenorphine. Patients randomly assigned to
buprenorphine had signifcantly lower relapse
rates during 24 weeks of outpatient treatment
than patients assigned to XR-NTX.45 This fnding
resulted from challenges in completing XR-NTX
induction, such that a signifcant proportion
of patients did not actually receive XR-NTX.
However, when comparing only those partici-
pants who started their assigned medication, no
signifcant between-group differences in relapse
rates were observed. Because dose induction
was conducted with inpatients, fndings may not
be generalizable to dose induction in outpatient
settings, where most patients initiate treatment.
A 12-week trial among adults with opioid de-
pendence in Norway who were opioid abstinent
at the time of random assignment found that
XR-NTX was as effective as buprenorphine in
retaining patients in treatment and in reducing
illicit opioid use.46
Oral naltrexone is also available, but it has not
been found to be superior to placebo or to no
medication in clinical trials.47 Nonadherence
limits its use.
Buprenorphine
Buprenorphine in its sublingual form retains
patients in treatment and reduces illicit opioid
use more effectively than placebo.48 It also
reduces HIV risk behaviors.49,50 A multisite
randomized trial with individuals addicted to
prescription opioids showed that continued
buprenorphine was superior to buprenorphine
dose taper in reducing illicit opioid use.51
Another randomized trial showed that continued
buprenorphine also improved treatment
retention and reduced illicit prescription opioid
use compared with buprenorphine dose taper.52
Long-term studies of buprenorphine show its
effectiveness outside of clinical research proto-
cols.53,54 Naloxone, a short-acting opioid antago-
nist, is also often included in the buprenorphine
formulation to help prevent diversion to injected
misuse. Because of the evidence of buprenor-
phine’s effectiveness, WHO lists it as
an essential medication.55 Buprenorphine is
available in “transmucosal” (i.e., sublingual or
buccal) formulations.
Buprenorphine implants can be effective
in stable patients. FDA approved implants
(Probuphine) after a clinical trial showed them
to be as effective as relatively low-dose (i.e.,
8 mg or less daily) sublingual buprenorphine
(Suboxone equivalents) for patients who are
already clinically stable.56 More research is
needed to establish implants’ effectiveness
outside of research studies, but fndings to
date are promising.57,58
FDA approved buprenorphine extended-
release injection (Sublocade) in November
2017 to treat patients with moderate
or severe OUD who have frst received
treatment with transmucosal buprenorphine
for at least 1 week. This buprenorphine formu-
lation is a monthly subcutaneous injection.
Exhibit 1.2 compares medications for OUD.
1-7
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
Cost Efectiveness and Cost Benefts
Cost-effectiveness and cost-beneft analyses can
further our understanding of OUD medications’
effectiveness.
Data indicate that medications for OUD are
cost effective. Cost-effectiveness analyses
compare the cost of different treatments with
their associated outcomes (e.g., negative opioid
urine tests). Such analyses have found that:
• Methadone and buprenorphine are more
cost effective than OUD treatment without
medication.59
• Counseling plus buprenorphine leads to
signifcantly lower healthcare costs than little
or no treatment among commercially insured
patients with OUD.60
• Treatment with any of the three OUD medi-
cations this TIP covers led to lower healthcare
usage and costs than treatment without
medication in a study conducted in a large
health plan.61
Relatively few cost-beneft analyses have
examined addiction treatment with medi-
cation separately from addiction treatment
in general.62 Cost-beneft studies compare a
treatment’s cost with its benefts. The treatment
is cost benefcial if its benefts outweigh its cost.
These benefts can include:
• Reduced expenditures because of decreased
crime.
• Reduced expenditures related to decreases in
the use of the justice system.
• Improved quality of life.
• Reduced healthcare spending.
• Greater earned income.
Methadone treatment in OTPs can reduce justice
system and healthcare costs.63,64
Requirements and Regulations
Following is a summary of regulations and
requirements that apply to the three OUD
medications. Part 3 of this TIP discusses the
pharmacology and dosing of these medications.
Only federally certifed and accredited OTPs
can dispense methadone for the treatment of
OUD. Methadone is typically given orally as a
liquid.65
OTPs can dispense buprenorphine under OTP
regulations without using a federal waiver.
Individual healthcare practitioners can
prescribe buprenorphine in any medical
setting, as long as they apply for and receive
waivers of the special registration requirements
defned in the Controlled Substances Act.
Several laws and regulations contain information
about which healthcare practitioners are eligible
to apply for a waiver and how to qualify
(www.samhsa.gov/medication-assisted-treat-
ment/training-materials-resources/apply-for-
practitioner-waiver). This information
is summarized below.
• Eligible physicians, nurse practitioners,
physician assistants, and other qualifying
practitioners (clinical nurse specialists,
certifed registered nurse anesthetists,
and certifed nurse midwives) can apply
for a waiver.
• At present, clinical nurse specialists, certifed
registered nurse anesthetists, and certifed
nurse midwives are only eligible to apply for
a waiver until October 1, 2023.
• For the frst year of waiver use, all providers
can treat up to 30 patients at one time.
However, providers who satisfy additional
practice and reporting requirements, and
physicians who are board certifed in addiction
psychiatry or addiction medicine, may request
to treat up to 100 patients at a time in the frst
year of waiver use. Additionally, practitioners
who provide MAT in “qualifed practice
settings,” as defned in title 42, section 8.615
of the Code of Federal Regulations, may also
request to treat up to 100 patients within the
frst year.
• After the frst year of waiver use, all providers
may request to increase their patient limit
to 100.
1-8
Medications for Opioid Use Disorder TIP 63
• Physicians and other qualifed providers who
are board certifed in addiction psychiatry or
addiction medicine or who satisfy additional
practice and reporting requirements may
apply to increase their patient limit to 275
after a year at the 100-patient limit.
Prescribing buprenorphine implants requires
Probuphine REMS Program certifcation.
Providers who wish to insert or remove
implants must obtain live training and certif-
cation in the REMS Program.
Healthcare settings and pharmacies must get
Sublocade REMS Program certifcation to
dispense this medication and can only dispense
it directly to healthcare providers for subcutane-
ous administration.
RESOURCE ALERT
OUD Medication Treatment Limits
and Reporting Requirements
The following websites provide information
about the Department of Health and Human
Services' (1) fnal rule to increase patient
access to medication for OUD, (2) notice on
Practice Guidelines for the Administration
of Buprenorphine for Treating Opioid Use
Disorder, and (3) associated reporting
requirements:
www.federalregister.gov/documents/2016/
07/08/2016-16120/medication-assisted-
treatment-for-opioid-use-disorders
www.federalregister.gov/documents/
2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-
for-treating-opioid-use-disorder
www.samhsa.gov/sites/default/fles/
programs_campaigns/medication_assisted/
understanding-patient-limit275.pdf
Naltrexone has no regulations beyond those
that apply to any prescription pharmaceuti-
cal. Any healthcare provider with prescribing
authority, including those practicing in OTPs, can
prescribe its oral formulation and administer its
long-acting injectable formulation.
The Controlled Substances Act contains a few
exceptions from the requirement to provide
methadone through an OTP or buprenorphine
through an OTP or a waivered practitioner.
These include (1) administering (not prescribing)
an opioid for no more than 3 days to a patient
in acute opioid withdrawal while preparations
are made for ongoing care and (2) administering
opioid medications in a hospital to maintain or
detoxify a patient as an “incidental adjunct to
medical or surgical treatment of conditions other
than addiction.”66
Duration of Treatment With OUD
Medication
Patients can take medication for OUD on
a short-term or long-term basis. However,
patients who discontinue OUD medication
generally return to illicit opioid use. Why is this
so, even when discontinuation occurs slowly and
carefully? Because the more severe form of OUD
(i.e., addiction) is more than physical depen-
dence. Addiction changes the reward circuitry
of the brain, affecting cognition, emotions,
and behavior. Providers and their patients
should base decisions about discontinuing OUD
medication on knowledge of the evidence base
for the use of these medications, individualized
assessments, and an individualized treatment plan
they collaboratively develop and agree upon.
Arbitrary time limits on the duration of treatment
with OUD medication are inadvisable.
Maintenance Treatment
The best results occur when a patient receives
medication for as long as it provides a beneft.
This approach is often called “maintenance
treatment.”67,68 Once stabilized on OUD med-
ication, many patients stop using illicit opioids
completely. Others continue to use for some
1-9
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
time, but less frequently and in smaller amounts,
which reduces their risk of morbidity and
overdose death.
OUD medication gives people the time
and ability to make necessary life changes
associated with long-term remission and
recovery (e.g., changing the people, places, and
things connected with their drug use), and to
do so more safely. Maintenance treatment also
minimizes cravings and withdrawal symptoms.
And it lets people better manage other aspects
of their life, such as parenting, attending school,
or working.
Medication Taper
After some time, patients may want to stop
opioid agonist therapy for OUD through
gradually tapering doses of the medication.
Their outcomes will vary based on factors such
as the length of their treatment, abstinence
from illicit drugs, fnancial and social stability,
and motivation to discontinue medication.69
Longitudinal studies show that most patients who
try to stop methadone treatment relapse during
or after completing the taper.70,71 For example,
in a large, population-based retrospective
study, only 13 percent of patients who tapered
from methadone had successful outcomes (no
treatment reentry, death, or opioid-related
hospitalization within 18 months after taper).72
A clinical trial of XR-NTX versus treatment
without medication also found increased risk of
returning to illicit opioid use after discontinuing
medication.73
Adding psychosocial treatments to taper
regimens may not signifcantly improve
outcomes compared with remaining on med-
ication. One study randomly assigned partici-
pants to methadone maintenance or to 6 months
of methadone treatment with a dose taper plus
intensive psychosocial treatment. The mainte-
nance group had more days in treatment and
lower rates of heroin use and HIV risk behavior
at 12-month follow-up.74 Patients wishing to
taper their opioid agonist medication should
be offered psychosocial and recovery support
Primary care physicians are on the
front lines of providing offce-based
treatment with medication for OUD.
services. They should be monitored during and
after dose taper, offered XR-NTX, and encouraged
to resume treatment with medication quickly if
they return to opioid use.
Medically Supervised Withdrawal
Medically supervised withdrawal is a process in
which providers offer methadone or buprenor-
phine on a short-term basis to reduce physical
withdrawal signs and symptoms. Formerly called
detoxifcation, this process gradually decreases
the dose until the medication is discontinued,
typically over a period of days or weeks. Studies
show that most patients with OUD who undergo
medically supervised withdrawal will start using
opioids again and won’t continue in recom-
mended care.75, 76, 77, 78, 79, 80, 81, 82, 83 Psychosocial
treatment strategies, such as contingency
management, can reduce dropout from medically
supervised withdrawal, opioid use during with-
drawal, and opioid use following completion of
withdrawal.84 Medically supervised withdrawal is
necessary for patients starting naltrexone, which
requires at least 7 days without short-acting
opioids and 10 to 14 days without long-acting
opioids.
Patients who complete medically supervised
withdrawal are at risk of opioid overdose.
Treatment Settings
Almost all healthcare settings are appropriate
for screening and assessing for OUD and
offering medication onsite or by referral.
Settings that offer OUD treatment have expanded
from specialty sites (certifed OTPs, residential fa-
cilities, outpatient addiction treatment programs,
and addiction specialist physicians’ offces) to
general primary care practices, health centers,
emergency departments, inpatient medical and
psychiatric units, jails and prisons, and other
settings.
1-10
Medications for Opioid Use Disorder TIP 63
Sustained public health efforts are
essential to address the urgent need for
OUD treatment and the risk of related
overdose, HIV, and hepatitis C virus
epidemics. These efforts must remove
barriers and increase access to OUD
medication.
OUD medications should be available to
patients across all settings and at all levels
of care—as a tool for remission and recovery.
Because of the strength of the science, a 2016
report from the Surgeon General85 urged
adoption of medication for OUD along with
recovery supports and other behavioral health
services throughout the healthcare system.
Challenges to Expanding Access
to OUD Medication
Despite the urgent need for treatment
throughout the United States, only about 21.5
percent of people with OUD received treatment
from 2009 to 2013.86 The Centers for Disease
Control and Prevention lists more than 200 U.S.
counties as at risk for an HIV or a hepatitis C
virus outbreak related to injection drug use.87
Resources
Patient success stories are inspirational. They
highlight the power of OUD medication to help
people achieve remission and recovery. See the
“Patient Success Stories” section in Part 5 of this
TIP.
Part 5 of this TIP also contains community
resources and advocacy resources. The
community resources are for OTP, addiction
treatment, and offce-based providers. The
advocacy resources can help patients and others
advocate for OUD medication for themselves
and in their communities.
1-11
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
Notes
1 World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment
of opioid dependence. Geneva, Switzerland: WHO
Press.
2 Council of Economic Advisers. (2017). The
underestimated cost of the opioid crisis. Washington,
DC: Executive Offce of the President of the United
States.
3 American Society of Addiction Medicine. (2011).
Defnition of addiction. Retrieved January 9, 2018, from
www.asam.org/resources/defnition-of-addiction
4 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
5 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
6 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
7 National Cancer Institute. (n.d.). Remission. In NCI
dictionary of cancer terms. Retrieved November 22,
2017, from www.cancer.gov/publications/dictionaries
/cancer-terms?cdrid=45867
8 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
9 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011, April 30).
Injectable extended-release naltrexone for opioid
dependence: A double-blind, placebo-controlled,
multicentre randomised trial. Lancet, 377(9776),
1506–1513.
10 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
11 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
12 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2),
1–84.
13 Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède,
J. P., & Tignol, J. (2004). French feld experience with
buprenorphine. American Journal on Addictions,
13(Suppl. 1), S17–S28.
14 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
15 Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
16 Schwartz, R. P., Gryczynski, J., O’Grady, K. E., Sharfstein,
J. M., Warren, G., Olsen, Y., … Jaffe, J. H. (2013). Opioid
agonist treatments and heroin overdose deaths in
Baltimore, Maryland, 1995–2009. American Journal of
Public Health, 103(5), 917–922.
17 World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment
of opioid dependence. Geneva, Switzerland: WHO
Press.
18 Brezing, C., & Bisaga, A. (2015, April 30). Opioid use
disorder: Update on diagnosis and treatment. Psychiatric
Times, 32(4) 1–4.
19 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
20 Jones, C. M., Campopiano, M., Baldwin, G., & McCance-
Katz, E. (2015). National and state treatment need
and capacity for opioid agonist medication-assisted
treatment. American Journal of Public Health, 105(8),
e55–e63.
21 Blue Cross Blue Shield. (2017). America’s opioid epidemic
and its effect on the nation’s commercially insured
population. Washington, DC: Blue Cross Blue Shield
Association.
22 Jones, C. M., Campopiano, M., Baldwin, G., & McCance-
Katz, E. (2015). National and state treatment need
and capacity for opioid agonist medication-assisted
treatment. American Journal of Public Health, 105(8),
e55–e63.
23 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2),
1–84.
24 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., … Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence:
A randomized controlled trial. JAMA, 283(10),
1303–1310.
1-12
Medications for Opioid Use Disorder TIP 63
25 Nielsen, S., Larance, B., Degenhardt, L., Gowing,
L., Kehler, C., & Lintzeris, N. (2016). Opioid agonist
treatment for pharmaceutical opioid dependent people.
Cochrane Database of Systematic Reviews, 2016(5),
1–61.
26 Amato, L., Davoli, M., Perucci, C. A., Ferri, M., Faggiano,
F., & Mattick, R. P. (2005). An overview of systematic
reviews of the effectiveness of opiate maintenance
therapies: Available evidence to inform clinical practice
and research. Journal of Substance Abuse Treatment,
28(4), 321–329.
27 Faggiano, F., Vigna-Taglianti, F., Versino, E., & Lemma, P.
(2003). Methadone maintenance at different dosages for
opioid dependence. Cochrane Database of Systematic
Reviews, 2003(3), 1–45.
28 Herget, G. (2005). Methadone and buprenorphine added
to the WHO list of essential medicines. HIV/AIDS Policy
and Law Review, 10(3), 23–24.
29 Gossop, M., Marsden, J., Stewart, D., & Kidd, T. (2003).
The National Treatment Outcome Research Study
(NTORS): 4–5 year follow-up results. Addiction, 98(3),
291–303.
30 Lawrinson, P., Ali, R., Buavirat, A., Chiamwongpaet, S.,
Dvoryak, S., Habrat, B., … Zhao, C. (2008). Key fndings
from the WHO collaborative study on substitution
therapy for opioid dependence and HIV/AIDS. Addiction,
103(9), 1484–1492.
31 Teesson, M., Ross, J., Darke, S., Lynskey, M., Ali, R., Ritter,
A., & Cooke, R. (2006). One year outcomes for heroin
dependence: Findings from the Australian Treatment
Outcome Study (ATOS). Drug and Alcohol Dependence,
83(2), 174–180.
32 Bruce, R. D. (2010). Methadone as HIV prevention: High
volume methadone sites to decrease HIV incidence rates
in resource limited settings. International Journal on Drug
Policy, 21(2), 122–124.
33 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., … Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
34 Gowing, L., Farrell, M. F., Bornemann, R., Sullivan, L. E.,
& Ali, R. (2011). Oral substitution treatment of injecting
opioid users for prevention of HIV infection. Cochrane
Database of Systematic Reviews, 2011(8), 1–117.
35 MacArthur, G. J., Minozzi, S., Martin, N., Vickerman, P.,
Deren, S., Bruneau, J., … Hickman, M. (2012). Opiate
substitution treatment and HIV transmission in people
who inject drugs: Systematic review and meta-analysis.
BMJ, 345, e5945.
36 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
37 Metzger, D. S., & Zhang, Y. (2010). Drug treatment as HIV
prevention: Expanding treatment options. Current HIV/
AIDS Reports, 7(4), 220–225.
38 Woody, G. E., Bruce, D., Korthuis, P. T., Chhatre, S.,
Poole, S., Hillhouse, M., … Ling, W. (2014). HIV risk
reduction with buprenorphine-naloxone or methadone:
Findings from a randomized trial. Journal of Acquired
Immune Defciency Syndromes, 66(3), 288–293.
39 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., … Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
40 Schwartz, R. P., Jaffe, J. H., O’Grady, K. E., Kinlock, T. W.,
Gordon, M. S., Kelly, S. M., … Ahmed, A. (2009). Interim
methadone treatment: Impact on arrests. Drug and
Alcohol Dependence, 103(3), 148–154.
41 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
42 Comer, S. D., Sullivan, M. A., Yu, E., Rothenberg, J. L.,
Kleber, H. D., Kampman, K., … O’Brien, C. P. (2006).
Injectable, sustained-release naltrexone for the treatment
of opioid dependence: A randomized, placebo-
controlled trial. Archives of General Psychiatry, 63(2),
210–218.
43 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011, April 30).
Injectable extended-release naltrexone for opioid
dependence: A double-blind, placebo-controlled,
multicentre randomised trial. Lancet, 377(9776),
1506–1513.
44 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
45 Lee, J. D., Nunes, E. V., Jr., Novo, P., Bachrach, K., Bailey,
G. L., Bhatt, S., … Rotrosen, J. (2018). Comparative
effectiveness of extended-release naltrexone versus
buprenorphine-naloxone for opioid relapse prevention
(X:BOT): A multicentre, open-label, randomised
controlled trial. Lancet, 391(10118), 309–318.
46 Tanum, L., Solli, K. K., Latif, Z. E., Benth, J. Š., Opheim,
A., Sharma-Haase, K., … Kunøe, N. (2017). Effectiveness
of injectable extended-release naltrexone vs daily
buprenorphine-naloxone for opioid dependence: A
randomized clinical noninferiority trial. JAMA Psychiatry,
74(12), 1197–1205.
1-13
TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment
47 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(2), 1–45.
48 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2),
1–84.
49 Edelman, E. J., Chantarat, T., Caffrey, S., Chaudhry, A.,
O’Connor, P. G., Weiss, L., … Fiellin, L. E. (2014). The
impact of buprenorphine/naloxone treatment on HIV
risk behaviors among HIV-infected, opioid-dependent
patients. Drug and Alcohol Dependence, 139,
79–85.
50 Sullivan, L. E., Moore, B. A., Chawarski, M. C., Pantalon,
M. V., Barry, D., O’Connor, P. G., … Fiellin, D. A. (2008).
Buprenorphine/naloxone treatment in primary care is
associated with decreased human immunodefciency virus
risk behaviors. Journal of Substance Abuse Treatment,
35(1), 87–92.
51 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
52 Fiellin, D. A., Schottenfeld, R. S., Cutter, C. J., Moore, B.
A., Barry, D. T., & O’Connor, P. G. (2014). Primary care-
based buprenorphine taper vs maintenance therapy for
prescription opioid dependence: A randomized clinical
trial. JAMA Internal Medicine, 174(12), 1947–1954.
53 Fiellin, D. A., Moore, B. A., Sullivan, L. E., Becker, W.
C., Pantalon, M. V., Chawarski, M. C., … Schottenfeld,
R. S. (2008). Long-term treatment with buprenorphine/
naloxone in primary care: Results at 2–5 years. American
Journal on Addictions, 17(2), 116–120.
54 Soeffng, J. M., Martin, L. D., Fingerhood, M. I.,
Jasinski, D. R., & Rastegar, D. A. (2009). Buprenorphine
maintenance treatment in a primary care setting:
Outcomes at 1 year. Journal of Substance Abuse
Treatment, 37(4), 426–430.
55 Herget, G. (2005). Methadone and buprenorphine added
to the WHO list of essential medicines. HIV/AIDS Policy
and Law Review, 10(3), 23–24.
56 Rosenthal, R. N., Lofwall, M. R., Kim, S., Chen, M., Beebe,
K. L., Vocci, F. J., & PRO-814 Study Group. (2016). Effect
of buprenorphine implants on illicit opioid use among
abstinent adults with opioid dependence treated with
sublingual buprenorphine: A randomized clinical trial.
Journal of the American Medical Association, 316(3),
282–290.
57 Rosenthal, R. N., Lofwall, M. R., Kim, S., Chen, M., Beebe,
K. L., & Vocci, F. J. (2016). Effect of buprenorphine
implants on illicit opioid use among abstinent adults
with opioid dependence treated with sublingual
buprenorphine: A randomized clinical trial. JAMA, 316(3),
282–290.
58 Barnwal, P., Das, S., Mondal, S., Ramasamy, A., Maiti, T.,
& Saha, A. (2017). Probuphine® (buprenorphine implant):
Promising candidate in opioid dependence. Therapeutic
Advances in Psychopharmacology, 7(3), 119–134.
59 Connock, M., Juarez-Garcia, A., Jowett, S., Frew, E.,
Liu, Z., Taylor, R. J., … Taylor, R. S. (2007, March).
Methadone and buprenorphine for the management of
opioid dependence: A systematic review and economic
evaluation. Health Technology Assessment, 11(9), 1–171,
iii–iv.
60 Lynch, F. L., McCarty, D., Mertens, J., Perrin, N. A., Green,
C. A., Parthasarathy, S., … Pating, D. (2014). Costs of
care for persons with opioid dependence in commercial
integrated health systems. Addiction Science and Clinical
Practice, 9, 16.
61 Baser, O., Chalk, M., Fiellin, D. A., & Gastfriend, D.
R. (2011). Cost and utilization outcomes of opioid-
dependence treatments. American Journal of Managed
Care, 17(Suppl. 8), S235–S248.
62 Schwartz, R. P., Alexandre, P. K., Kelly, S. M., O’Grady,
K. E., Gryczynski, J., & Jaffe, J. H. (2014). Interim versus
standard methadone treatment: A beneft-cost analysis.
Journal of Substance Abuse Treatment, 46(3), 306–314.
63 Cartwright, W. S. (2000). Cost-beneft analysis of drug
treatment services: Review of the literature. Journal of
Mental Health Policy and Economics, 3(1), 11–26.
64 McCollister, K. E., & French, M. T. (2003). The relative
contribution of outcome domains in the total economic
beneft of addiction interventions: A review of frst
fndings. Addiction, 98(12), 1647–1659.
65 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
66 Drug Enforcement Administration. (n.d.). Title 21 Code of
Federal Regulations. Part 1306—Prescriptions. §1306.07
Administering or dispensing of narcotic drugs. Retrieved
November 22, 2017, from www
.deadiversion.usdoj.gov/21cfr/cfr/1306/1306_07.htm
67 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
68 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
1-14
Medications for Opioid Use Disorder TIP 63
69 Calsyn, D. A., Malcy, J. A., & Saxon, A. J. (2006). Slow
tapering from methadone maintenance in a program
encouraging indefnite maintenance. Journal of
Substance Abuse Treatment, 30, 159–163.
70 Stimmel, B., Goldberg, J., Rotkopf, E., & Cohen, M.
(1977). Ability to remain abstinent after methadone
detoxifcation. JAMA, 237, 1216–1220.
71 Cushman, P. (1978). Abstinence following detoxifcation
and methadone maintenance treatment. American
Journal of Medicine, 65, 46–52.
72 Nosyk, B., Sun, H., Evans, E., Marsh, D. C., Anglin, M. D.,
Hser, Y. I., & Anis, A. H. (2012). Defning dosing pattern
characteristics of successful tapers following methadone
maintenance treatment: Results from a population-based
retrospective cohort study. Addiction, 107(9), 1621–1629.
73 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
74 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., … Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence: A
randomized controlled trial. JAMA, 283(10), 1303–1310.
75 Wines, J. D., Jr., Saitz, R., Horton, N. J., Lloyd-Travaglini,
C., & Samet, J. H. (2007). Overdose after detoxifcation:
A prospective study. Drug and Alcohol Dependence,
89(2–3), 161–169.
76 Strang, J., McCambridge, J., Best, D., Beswick, T., Bearn,
J., Rees, S., & Gossop, M. (2003). Loss of tolerance and
overdose mortality after inpatient opiate detoxifcation:
Follow up study. British Medical Journal, 326(7396),
959–960.
77 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
78 Ling, W., Amass, L., Shoptaw, S., Annon, J. J., Hillhouse,
M., Babcock, D., … Ziedonis, D. (2005). A multi-center
randomized trial of buprenorphine-naloxone versus
clonidine for opioid detoxifcation: Findings from the
National Institute on Drug Abuse Clinical Trials Network.
Addiction, 100(8), 1090–1100.
79 McCusker, J., Bigelow, C., Luippold, R., Zorn, M., & Lewis,
B. F. (1995). Outcomes of a 21-day drug detoxifcation
program: Retention, transfer to further treatment, and
HIV risk reduction. American Journal of Drug and Alcohol
Abuse, 21(1), 1–16.
80 Fiellin, D., Schottenfeld, R., Cutter, C., Moore, A.,
Barry, D., & O’Connor, P. (2014). Primary care based
buprenorphine taper vs maintenance therapy for
prescription opioid dependence: A randomized clinical
trial. JAMA Internal Medicine, 174(12), 1947–1954.
81 Gruber, V., Delucchi, K., Kielstein, A., & Batki, S.
(2008). A randomized trial of six-month methadone
maintenance with standard or minimal counseling versus
21-day methadone detoxifcation. Drug and Alcohol
Dependence, 94, 199.
82 Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter,
J., Thomas, C., … Bilangi, R. (2009). Buprenorphine
tapering schedule and illicit opioid use. Addiction, 104(2),
256–265.
83 Smyth, B. P., Barry, J., Keenan, E., & Ducray, K. (2010).
Lapse and relapse following inpatient treatment of opiate
dependence. Irish Medical Journal, 103(6), 176–179.
84 Amato, L., Minozzi, S., Davoli, M., & Vecchi, S. (2011).
Psychosocial and pharmacological treatments versus
pharmacological treatments for opioid detoxifcation.
Cochrane Database of Systematic Reviews, 2011(9), 1–55.
85 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
86 Saloner, B., & Karthikeyan, S. (2015). Changes in
substance abuse treatment use among individuals with
opioid use disorders in the United States, 2004–2013.
JAMA, 314(14), 1515–1517.
87 Van Handel, M. M., Rose, C. E., Hallisey, E. J., Kolling, J.
L., Zibbell, J. E., Lewis, B., … Brooks, J. T. (2016). County-
level vulnerability assessment for rapid dissemination of
HIV or HCV infections among persons who inject drugs,
United States. Journal of Acquired Immune Defciency
Syndromes, 73(3), 323–331.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Part 2: Addressing Opioid Use Disorder in General Medical Settings
For Healthcare Professionals
Part 2 of this Treatment Improvement Protocol (TIP) will guide practitioners’ efforts to identify,
assess, and treat or refer patients with opioid use disorder (OUD) in general medical settings.
TIP Navigation
Executive Summary
For healthcare and addiction professionals,
policymakers, patients, and families
Part 1: Introduction to Medications for Opioid
Use Disorder Treatment
For healthcare and addiction professionals,
policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment
Counselors, Clients, and Healthcare
Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medication for
Opioid Use Disorder
For healthcare and addiction professionals,
policymakers, patients, and families
KEY MESSAGES
• All healthcare practices should screen
for alcohol, tobacco, and other substance
misuse (including opioid misuse).
• Validated screening tools, symptom
surveys, and other resources are readily
available; this part lists many of them.
• When patients screen positive for risk of
harm from substance use, practitioners
should assess them using tools that
determine whether substance use meets
diagnostic criteria for a substance use
disorder (SUD).
• Thorough assessment should address
patients’ medical, social, SUD, and family
histories.
• Laboratory tests can inform treatment
planning.
• Practitioners should develop treatment
plans or referral strategies (if onsite SUD
treatment is unavailable) for patients
who need SUD treatment.
2-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 2 of 5
Contents
Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1
Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1
Alcohol Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3
Tobacco Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-5
Drug Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-5
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8
Determine the Need for and Extent of Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8
Set the Stage for Successful Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8
Take a Complete History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-9
Conduct a Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-12
Obtain Appropriate Laboratory Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-13
Review the PDMP. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-16
Determine Diagnosis and Severity of OUD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17
Treatment Planning or Referral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17
Making Decisions About Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17
Understanding Treatment Settings and Services. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-18
Outpatient OUD Treatment Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-18
Determining OUD Service Intensity and Ensuring Follow-Through . . . . . . . . . . . . . . . . . . 2-23
Preventing Opioid-Related Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-26
Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Alcohol and Drug Use Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Tobacco Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Buprenorphine Treatment Locator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Buprenorphine Training, Mentorship,
and Waivers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28
Medication Treatment for OUD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29
Syringe Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29
Opioid-Related Overdose Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29
Opioid Withdrawal Scales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30
Patient and Family Education on Medications To Treat OUD . . . . . . . . . . . . . . . . . . . . . . . 2-30
Referral and Treatment Locators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30
Screening, Assessment, and Drug Testing Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30
Treatment Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-31
2-iii
TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 2 of 5
Part 2 Appendix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32
Stable Resource Toolkit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32
Drug Abuse Screening Test (DAST-10) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-34
DSM-5 Opioid Use Disorder Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-35
TAPS Tool Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-36
TAPS Tool Part 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-37
Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-39
This page intentionally left blank.
2-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
PART 2 of 5
Addressing Opioid Use Disorder in General
Medical Settings
Part 2 of this TIP is for healthcare professionals who work in general medical settings* and care
for patients who misuse opioids or have OUD. Healthcare professionals in such settings address
most personal healthcare needs, develop sustained partnerships with patients, and practice in
the context of family and community. Thus, they have a good basis from which to understand
patients’ needs related to OUD screening, assessment, and treatment (or referral to specialty
treatment).
Scope of the Problem
The number of patients presenting with OUD
in medical clinics, community health centers,
and private practices is increasing. Healthcare
professionals in these general settings are in
an important position to identify, assess, and
treat OUD or to refer patients for treatment.
Moreover, patients who are medically and
mentally stable can beneft from receiving OUD
medications in integrated care settings, where
they often have already established therapeutic
relationships with their healthcare providers.
Exhibit 2.1 defnes key terms in Part 2. For more
defnitions, see the glossary in Part 5 of this TIP.
Screening
Screening can identify patients who may
have diseases or conditions related to their
substance use. Health care in general medical
settings routinely includes screening for
common, treatable conditions such as cancer
that are associated with signifcant morbidity and
mortality. Screening for SUDs is important, as
misuse of alcohol, tobacco, and other substances
is common among patients in medical settings
(Exhibit 2.2).1
An estimated 1.4M
AMERICANS
have OUD related to
opioid painkillers;
438K have heroin-
related OUD.2
Screening can identify substance misuse in
patients who wouldn’t otherwise discuss it
or connect it with the negative consequences
they’re experiencing. Some patients may
spontaneously reveal their substance use and
ask for help. This is more likely when they’re
experiencing harmful consequences of substance
use. However, screening may identify unhealthy
substance use (e.g., binge drinking) and SUDs
The TIP expert panel recommends
that healthcare professionals
screen patients for alcohol, tobacco,
prescription drug, and illicit drug use
at least annually.
*In this TIP, the term “general medical setting” includes medical clinics, community health centers, and private practices.
2-2
Medications for Opioid Use Disorder TIP 63
EXHIBIT 2.1. Key Terms
Addiction: As defned by the American Society of Addiction Medicine (ASAM),3 “a primary, chronic
disease of brain reward, motivation, memory, and related circuitry.” It is characterized by inability to
consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant
problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response.
Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic
and Statistical Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic
purposes, but it commonly describes the more severe forms of OUD.
Healthcare professionals: Physicians, nurse practitioners (NPs), physician assistants (PAs), and
other medical service professionals who are eligible to prescribe medications for and treat patients with
OUD (i.e., until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, certifed
nurse midwives). The term “prescribers” also refers to these healthcare professionals.
Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs
and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as
with the typical standard of care in medical and psychiatric treatment of other chronic illnesses).
Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an
alpha-2 adrenergic agonist if an opioid agonist is not available) in tapering doses or other medications to
help a patient discontinue illicit or prescription opioids.
Medical management: Process whereby healthcare professionals provide medication, basic brief
supportive counseling, monitoring of drug use and medication adherence, and referrals, when necessary,
to addiction counseling and other services to address the patient’s medical, mental health, comorbid
addiction, and psychosocial needs.
Offce-based opioid treatment (OBOT): Providing medication for OUD in outpatient settings
other than certifed opioid treatment programs (OTPs).
Opioid misuse: The use of prescription opioids in any way other than as directed by a prescriber; the
use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5
Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at
cell receptors in the central nervous system that are normally stimulated by opioids. Mu-opioid receptor
full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those
produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid
receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists,
increasing their dose may not produce additional effects once they have reached their maximal effect. At
low doses, partial agonists may produce effects similar to those of full agonists.
Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the central
nervous system without producing the physiological effects of opioid agonists. Mu-opioid receptor
antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids.
Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and
Mental Health Services Administration (SAMHSA) certifcation and Drug Enforcement Administration
(DEA) registration to administer and dispense opioid agonist medications that are approved by the
Food and Drug Administration (FDA) to treat opioid addiction. Currently, these include methadone and
buprenorphine products. Other pharmacotherapies, such as naltrexone, may be provided but are not
subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational,
and other assessment and treatment services either onsite or by referral to an outside agency or
practitioner through a formal agreement.6
Continued on next page
2-3
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.1. Key Terms (continued)
Opioid use disorder (OUD): Per DSM-5,7 a disorder characterized by loss of control of opioid use,
risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do
not count toward the diagnosis in people experiencing these symptoms when using opioids under
appropriate medical supervision. OUD covers a range of severity and replaces what the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, termed “opioid abuse” and “opioid dependence.”
An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11
symptoms in a 12-month period. (See Exhibit 2.13 and the Appendix in Part 2 for full DSM-5 diagnostic
criteria for OUD.)
Recovery: A process of change through which individuals improve their health and wellness, live a
self-directed life, and strive to reach their full potential. Even individuals with severe and chronic SUDs
can, with help, overcome their SUDs and regain health and social function. Although abstinence from all
substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature.
Patients taking FDA-approved medication to treat OUD can be considered in recovery.
Relapse: A process in which a person with OUD who has been in remission experiences a return of
symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more
than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need
not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality.
Remission: A medical term meaning a disappearance of signs and symptoms of the disease.8 DSM-5
defnes remission as present in people who previously met OUD criteria but no longer meet any OUD
criteria (with the possible exception of craving).9 Remission is an essential element of recovery.
Return to opioid use: One or more instances of opioid misuse without a return of symptoms of
OUD. A return to opioid use may lead to relapse.
Tolerance: Alteration of the body’s responsiveness to alcohol or other drugs (including opioids) such
that higher doses are required to produce the same effect achieved during initial use. See also medically
supervised withdrawal.
before patients connect their substance use
with their presenting complaint. Screening is
also helpful when patients feel ashamed or afraid
to reveal their concerns spontaneously.
Every medical practice should determine
which screening tools to use and when, how,
and by whom they will be administered.
Each practice should also identify steps to take
when a patient screens positive. One effcient
workfow strategy is to have clinical assistants
or nurses administer the screening instrument in
an interview or provide patients with a paper or
computer tablet version for self-administration.
(Self-administration is generally as reliable as
interviewer administration.)10 Providers should be
nonjudgmental and rely on established rapport
when discussing screening results with patients.
The following sections summarize reliable
screening tools. (See Part 5 for more resources.)
Alcohol Screening
Screening for alcohol misuse can identify
patients at increased risk for opioid use.
When screening patients for opioid misuse,
providers should also screen for alcohol misuse
and alcohol use disorder (AUD), which cause
considerable morbidity and mortality.11 Providers
should warn patients who use opioids that
alcohol may increase opioid overdose risk.12 The
U.S. Preventive Services Task Force (USPSTF)
recommends screening adults for alcohol misuse,
including risky drinking and AUD. USPSTF also
recommends brief counseling for patients with
risky drinking.13,14
2-4
Medications for Opioid Use Disorder TIP 63
EXHIBIT 2.2. Substance Misuse and SUD Screening
Substance misuse screening
Negative Positive
Reinforce
healthy behavior
Assess substance use
and comorbidities
Substance misuse Substance
use disorder
Brief counseling Brief counseling and
treatment referral
Monitoring/follow up -
Consider
medication
If misuse continues, negotiate
a plan and refer to treatment
Ongoing assessment
and support
Adapted with permission.15
USPSTF recommends the following alcohol
screeners:
• The single-item National Institute on
Alcohol Abuse and Alcoholism (NIAAA)
Screener is the briefest tool available (Exhibit
2.3). It can help distinguish at-risk patients
who require further screening from those not
at risk for AUD. Encourage patients in the
latter category to maintain healthy behavior.
• The Alcohol Use Disorders Identifcation
Test (AUDIT)16 or its briefer version, the
AUDIT-Consumption,17 can elicit more in-
formation from patients who screen positive
on the single-item screener. The full AUDIT
tool (Exhibit 2.4) and its briefer version have
demonstrated acceptable reliability in AUD
screening.18 Assess patients with positive
screens for AUD.
Practitioners should consider medication and
referral to counseling for people with AUD.
The three FDA-approved medications to treat
AUD—acamprosate, disulfram, and naltrexone
(oral and extended-release injectable naltrex-
one [XR-NTX])—can be prescribed in general
medical and specialty SUD treatment settings.
(For more information on AUD treatment, see
the SAMHSA/NIAAA publication Medication for
the Treatment of Alcohol Use Disorder: A Brief
Guide.)19
2-5
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.3. NIAAA Single-Item Screener
How many times in the past year have you
had fve or more drinks in a day (four drinks
for women and all adults older than age 65)?
One or more times constitutes a positive
screen. Patients who screen positive
should have an assessment for AUD.
Adapted with permission.20
Tobacco Screening
More than 80 percent of patients who
are opioid dependent smoke cigarettes.21
Understanding of the major health conse-
quences and risks associated with tobacco use
has grown signifcantly over the past 50 years.
Among preventable causes of premature death,
smoking remains most prevalent, with more than
480,000 deaths per year in the United States.22 In
addition, more than 40 percent of all people who
smoke are mentally ill or have SUDs.23,24
USPSTF recommends that primary care
providers screen for tobacco use, advise
patients to quit, and provide counseling
and FDA-approved medications for tobacco
cessation.25 The six-item Fagerström Test for
Nicotine Dependence26 assesses cigarette use
and nicotine dependence. The maximum score
is 10; the higher the total score, the more severe
the patient’s nicotine dependence. The two-item
Heaviness of Smoking Index (Exhibit 2.5) is also
useful.27
Drug Screening
Screening for illicit drug use and prescription
medication misuse is clinically advantageous.
USPSTF’s position is that adults ages 18 and
older (including those who are pregnant) should
be routinely screened in primary care for illicit
drug use and prescription medication misuse
when services for accurate diagnosis, effective
treatment, and appropriate care can be offered
or referral can be provided.28 Identifying misuse
of prescription or illegal drugs can prevent
harmful drug interactions, lead to adjustments
in prescribing practices, improve medical care
adherence, and increase the odds of patients
getting needed interventions or treatment.29
Brief screening instruments for drug use
can determine which patients need further
assessment. Providers should reinforce healthy
behaviors among patients who report “no use”
and direct those who report “some use” for
further screening and assessment to obtain a
diagnosis.
Several brief screening instruments for drug
use can help primary care practitioners identify
patients who use drugs.30,31 For example, a
single-item screen is available for the general
public (Exhibit 2.6).32 A two-item valid screener
is available for use with U.S. veterans (Exhibit
2.7).33
Brief drug screens don’t indicate specifc
types of drugs used (nor does the longer
Drug Abuse Screening Test; see the Part 2
Appendix).34 If providers use nonspecifc screens,
they need to assess further which substances
patients use and to what degree.
The TIP expert panel recommends
universal OUD screening. Given the
high prevalence of SUDs in patients
visiting primary care settings and the
effectiveness of medications to treat
OUD specifcally, the TIP expert panel
recommends screening all patients for
opioid misuse.
2-6
Medications for Opioid Use Disorder TIP 63
EXHIBIT 2.4. AUDIT Screener
1. How often do you have a drink containing
alcohol?
(0) Never [Skip to Questions 9–10]
(1) Monthly or less
(2) 2 to 4 times a month
(3) 2 to 3 times a week
(4) 4 or more times a week
6. How often during the last year have you
needed an alcoholic drink frst thing in the
morning to get yourself going after a night of
heavy drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
2. How many drinks containing alcohol do you
have on a typical day when you are drinking?
(0) 1 or 2
(1) 3 or 4
(2) 5 or 6
(3) 7, 8, or 9
(4) 10 or more
7. How often during the last year have you had a
feeling of guilt or remorse after drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
3. How often do you have six or more drinks on
one occasion?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
Skip to Questions 9 and 10 if total score for
Questions 2 and 3 = 0
8. How often during the last year have you been
unable to remember what happened the night
before because you had been drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
4. How often during the last year have you found
that you were not able to stop drinking once
you had started?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
9. Have you or someone else been injured as a
result of your drinking?
(0) No
(2) Yes, but not in the last year
(4) Yes, during the last year
5. How often during the last year have you failed
to do what was normally expected from you
because of drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
10. Has a relative, friend, doctor, or another health
professional expressed concern about your
drinking or suggested you cut down?
(0) No
(2) Yes, but not in the last year
(4) Yes, during the last year
Note: Add up the points associated with answers. A score of 8 or more is considered a positive test for unhealthy drinking.
Adapted from material in the public domain.35 Available online (http://auditscreen.org).
2-7
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.5. Heaviness of
Smoking Index
Ask these two questions of current or recent
smokers:
1. How soon after waking do you smoke your
frst cigarette?
• Within 5 minutes (3 points)
• 5–30 minutes (2 points)
• 31–60 minutes (1 point)
• 61 or more minutes (no points)
2. How many cigarettes a day do you smoke?
• 10 or less (no points)
• 11–20 (1 point)
• 21–30 (2 points)
• 31 or more (3 points)
Total score:
1–2 points = very low dependence
3 points = low to moderate dependence
4 points = moderate dependence
5 or more points = high dependence
Adapted with permission.36
The Alcohol, Smoking, and Substance
Involvement Screening Test (ASSIST) screens
patients for all categories of substance
misuse, including alcohol and tobacco. This
World Health Organization (WHO) screener also
assesses substance-specifc risk. The ASSIST’s
length and rather complex scoring system have
hindered its adoption, but a computerized
version and a briefer hard copy version (ASSIST-
lite) make its use more effcient.37,38
The TIP expert panel does not
recommend routine universal drug
testing with urine, blood, or oral fuids
in primary care. Still, drug testing can
confrm recent drug use in patients
receiving diagnostic workups for
changes in mental status, seizures, or
other disorders. Conduct drug testing
before patients start OUD medication
and during treatment for monitoring.
EXHIBIT 2.6. Single-Item
Drug Screener
How many times in the past year have
you used an illegal drug or a prescription
medication for nonmedical reasons?
(A positive screen is 1 or more days.)
Reprinted with permission.39
EXHIBIT 2.7. Two-Item Drug
Use Disorder Screener for
Primary Care Clinics Serving
U.S. Veterans
Question 1: How many days in the past 12
months have you used drugs other than
alcohol? (A positive screen is 7 or more days.)
If fewer than 7, proceed with Question 2.
Question 2: How many days in the past 12
months have you used drugs more than you
meant to? (A positive screen is 2 or more days.)
Adapted with permission.40
(See the “Screening, Assessment, and Drug
Testing Resources” section for a link to a
modifed version of the ASSIST.)
Follow up any positive one-question screen
with a brief assessment. An example of a
two-step screening and brief assessment is the
Tobacco, Alcohol, Prescription Medications,
and Other Substance Use (TAPS Tool; see Part
2 Appendix), developed and tested in primary
care settings.41 This tool is based on the National
Institute on Drug Abuse (NIDA) Quick Screen
V1.042,43 and a modifed WHO ASSIST-lite.44
The TAPS Tool screens for clinically relevant
heroin and prescription opioid misuse (meeting
one or more DSM-5 SUD criteria) and misuse
of an array of other substances in primary care
patients. However, it may also detect SUDs only
for the most often-used substances (i.e., alcohol,
tobacco, and marijuana). Patients with positive
screens for heroin or prescription opioid misuse
need more indepth assessment.45
2-8
Medications for Opioid Use Disorder TIP 63
Assessment
Determine the Need for and Extent of
Assessment
Assess patients for OUD if:
• They screen positive for opioid misuse.
• They disclose opioid misuse.
• Signs or symptoms of opioid misuse are
present.
The extent of assessment depends on a
provider’s ability to treat patients directly.
If a provider does not offer medication, the
focus should be on medical assessment,
making a diagnosis of OUD, and patient
safety. This allows the provider to refer patients
to the appropriate level of treatment. The
provider can also conduct:
• Assessment and treatment for co-occurring
medical conditions or mental disorders
(including HIV and hepatitis C [anti-HCV]).
• Motivational brief interventions to promote
safer behavior and foster effective treatment
engagement.
• Overdose prevention education and provide
a naloxone prescription.
• Education for patients who inject drugs on
how to access sterile injecting equipment.
• An in-person follow-up, regardless of referral
to specialty treatment.
If the provider offers medication, the patient
needs more comprehensive assessment,
including:
• A review of the prescription drug monitoring
program (PDMP).
• A history, including a review of systems.
• A targeted physical exam for signs of opioid
withdrawal, intoxication, injection, and other
medical consequences of misuse.
• Determination of OUD diagnosis and severity.
• Appropriate laboratory tests in addition to
those recommended by the nontreating
provider (e.g., urine or oral fuid drug tests,
liver function tests, hepatitis B test).46
EVERYONE AGES
15 TO 65 should be
tested at least ONCE
for HIV . Persons at
HIGHER RISK, such as
people who useDRUGS
by injection, should be
tested ANNUALLY.
HIV
Hep C
Anyone who is injecting
or has ever INJECTED
DRUGS, even ONCE,
no matter how long
ago, should be TESTED
for HEPATITIS C,
r e g a r d l e s s o f t h e i r
i n t e n t i o n t o s e e k
TREATMENT for SUD .47,48
A comprehensive assessment is intended to:
• Establish the diagnosis of OUD.
• Determine the severity of OUD.
• Identify contraindicated medications.
• Indicate other medical conditions to address
during treatment.
• Identify mental and social issues to address.
Set the Stage for Successful Assessment
The medical setting should create a welcoming
environment that is nonjudgmental, respect-
ful, and empathetic. Many patients with OUD
are reluctant to discuss their opioid use in
medical settings.49 A welcoming environment can
2-9
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Open-ended, thought-provoking
questions encourage patients to
explore their own experiences. Ask
questions like “In what ways has
oxycodone affected your life?” or “What
could you do to prevent infections
like this in the future?” Closed-ended
questions with yes/no answers—like
“Has oxycodone caused your family
trouble?”—can seem judgmental to
patients who already feel ashamed
and defensive. Closed-ended questions
don’t help patients become aware of
and express their own circumstances
and motivations, nor do they encourage
patients to identify what they see as the
consequences of their substance use.
help patients feel safe disclosing facts they may
fnd embarrassing.50 Motivational interviewing
strategies, such as asking open-ended questions,
foster successful assessment.51 (Refer to TIP 34,
Brief Interventions and Brief Therapies for
Substance Abuse, for more specifc examples
of interview questions and responses.)52
Staff should explore patients’ ambivalence
and highlight problem areas to help them fnd
motivations for change. Almost all patients
have some ambivalence about their opioid
use. They will fnd some aspects pleasant and
benefcial, but others problematic, painful, or
destructive. By exploring that ambivalence
and highlighting problem areas, providers can
help patients discover their own motivations
for change. Motivational Interviewing: Helping
People Change53 discusses specifc applications
of motivational interviewing in health care.
Take a Complete History
Staff should prioritize medical, mental
health, substance use, and SUD treatment
histories. When obtaining patient histories, staff
should address these domains before starting
treatment. As providers and staff build trust over
future visits, they can get into more detailed
elements of the assessment.
Medical history
Taking a complete medical history of patients
with OUD is critical, as it is for patients with any
other medical condition treatable with medi-
cation. Asking about patients’ medical/surgical
history can:
• Reveal medical effects of substance use (e.g.,
endocarditis, soft tissue infection, hepatitis B
or C, HIV infection) that may need treatment.
• Highlight consequences that motivate change.
• Identify medical issues (e.g., severe liver
disease) that contraindicate or alter dosing
approaches for OUD pharmacotherapies.
• Reveal chronic pain issues.
• Help providers consider interactions among
various medications and other substances.
Exhibit 2.8 lists medical problems associated
with opioid misuse.
Mental health history
Assessing for comorbid mental illness is
critical. Mental illness is prevalent among people
with SUDs; it can complicate their treatment
and worsen their prognosis. In one study, nearly
20 percent of primary care patients with OUD
had major depression.54 SUDs can also mimic
or induce depression and anxiety disorders.
Although substance-induced depression and
anxiety disorders may improve with abstinence,
they may still require treatment in their own right
after a period of careful observation.55 Take a
history of the relationship between a patient’s
psychiatric symptoms and periods of substance
use and abstinence. Treatment for mental
disorders and SUDs can occur concurrently.
Substance use history
Substance use histories can help gauge OUD
severity, inform treatment planning, clarify
potential drug interactions, and highlight
the negative consequences of patients’
opioid use.
2-10
Medications for Opioid Use Disorder TIP 63
•
•
•
To help determine the severity of patients’
substance use, explore historical features of their
use, like:
Histories should also explore current patterns
of use,56 which inform treatment planning and
include:
• Age at frst use. Which drugs patients use.
Comorbid alcohol and tobacco use.
Frequency, recency, and intensity of use.
• Routes of ingestion (e.g., injection).
• History of tolerance, withdrawal, drug mixing,
and overdose.
EXHIBIT 2.8. Medical Problems Associated With Opioid Misuse57
CATEGORY POSSIBLE COMPLICATIONS
Cancer Injection drug use: Hepatocellular carcinoma related to hepatitis C
Cardiovascular Injection drug use: Endocarditis, septic thrombophlebitis
Endocrine/metabolic Opioids: Osteopenia, hypogonadism, erectile dysfunction, decreased sperm
motility, menstrual irregularity including amenorrhea, infertility
Hematologic Injection drug use/sharing intranasal use equipment: Hematologic
consequences of liver disease from hepatitis C, hepatitis C‐related
cryoglobulinemia and purpura
Hepatic Injection drug use/sharing intranasal use equipment: Hepatitis B, C, D;
infectious and toxic hepatitis
Infectious Opioids: Aspiration pneumonia, sexually transmitted infections
Injection drug use: Endocarditis, cellulitis, necrotizing fasciitis, pneumonia,
septic thrombophlebitis, mycotic aneurysm, septic arthritis (unusual joints,
such as sternoclavicular), osteomyelitis (including vertebral), epidural and brain
abscess, abscesses and soft tissue infections, mediastinitis, malaria, tetanus,
hepatitis B, hepatitis C, hepatitis D, HIV, botulism
Neurologic Opioids: Seizure (overdose and hypoxia), compression neuropathy (following
overdose), sleep disturbances
Nutritional Opioids: Protein malnutrition
Other gastrointestinal Opioids: Constipation, ileus, intestinal pseudo‐obstruction, sphincter of Oddi
spasm, nausea
Pulmonary Opioids: Respiratory depression/failure, bronchospasm, exacerbation of sleep
apnea, noncardiogenic pulmonary edema, bullae
Injection drug use: Pulmonary hypertension, talc granulomatosis, septic
pulmonary embolism, pneumothorax, emphysema, needle embolization
Renal Opioids: Rhabdomyolysis, acute renal failure (not direct toxic effect of
opioids but secondary to central nervous system depression and resulting
complications), factitious hematuria
Injection drug use: Focal glomerular sclerosis (HIV, heroin), glomerulonephritis
from hepatitis or endocarditis, chronic renal failure, amyloidosis, nephrotic
syndrome (hepatitis C)
2-11
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
To diagnose an SUD, assess patients’ negative
consequences of use, which can affect:
• Physical health.
• Mental health.
• Family relationships.
• Work/career status.
• Legal involvement.
• Housing status.
Buprenorphine and methadone can cause
complications for patients who misuse or have
SUDs involving alcohol or benzodiazepines.
Providers should take specifc histories on the
use of these substances.
SUD treatment history
Information about a patient’s past efforts
to get treatment or quit independently can
inform treatment planning. The same is true
for details about the events and behaviors that
led to a patient’s return to substance use after
periods of abstinence and remission of SUD.
Similarly, identifying the features of successful
quit attempts can help guide treatment plan
decisions. Such features may involve:
• Specifc treatment settings.
• Use of support groups.
• Previous responses to OUD medications.
Social history
Information about a patient’s social environ-
ments and relationships can aid treatment
planning. Social factors that may infuence
treatment engagement and retention, guide
treatment planning, and affect prognosis include:
• Transportation and child care needs.
• Adequacy and stability of housing.
• Criminal justice involvement.
• Employment status and quality of work
environment.
• Close/ongoing relationships with people with
SUDs.
• Details about drug use from people the
patient lives or spends time with (obtained
with patient’s consent).
Understanding patients’ motivations
for change can be more useful than
assessing “readiness” for change.
Patients coerced into treatment—such
as through parole and probation or
drug courts—are as likely to succeed
in treatment as patients engaging
voluntarily. Readiness fuctuates and
depends on context. Helping patients
explore why they want to change
their drug use can motivate them and
prepare their providers to support them
during assessment and treatment.
• Sexual orientation, identity, and history,
including risk factors for HIV/sexually transmit-
ted infections.
• Safety of the home environment. Substance
misuse substantially increases the risk of
intimate partner violence; screen all women
presenting for treatment for domestic
violence.58
Family history
Learn the substance use histories of patients’
parents, siblings, partners, and children. One
of the strongest risk factors for developing SUDs
is having a parent with an SUD. Genetic factors,
exposure to substance use in the household
during childhood, or both can contribute to the
development of SUDs.59
EXHIBIT 2.9. Signs of Opioid
Intoxication
Physical fndings
Drowsy but arousable
Sleeping intermittently (“nodding off”)
Constricted pupils
Mental status fndings
Slurred speech
Impaired memory or concentration
Normal to euphoric mood
2-12
Medications for Opioid Use Disorder TIP 63
PATIENT TESTIMONY
Opioid Withdrawal
“Severe opioid withdrawal isn’t
something I’d wish on my worst
enemy. The last time I went cold
turkey, I was determined to come off
all the way. The physical symptoms
were just the tip of the iceberg.
My mind was a nightmare that I
thought I would never wake up
from. There were times when I was
almost convinced that dying would
be better than what I was feeling. I
did not experience a moment of ease
for the frst 3 months, and it was 6
months until I started to feel normal.”
EXHIBIT 2.10. Physical Signs of
Opioid Withdrawal and Time to
Onset
STAGE GRADE
PHYSICAL
SIGNS/
SYMPTOMS
Conduct a Physical Examination
Perform a physical exam as soon as possible
if recent exam records aren’t accessible.
Assess for:
• Opioid intoxication or withdrawal.
• Physical signs of opioid use.
• Medical consequences of opioid use.
Exhibit 2.9 provides an overview of physical and
mental status fndings for opioid intoxication.
Opioid withdrawal
Opioid withdrawal can be extremely uncom-
fortable. Symptoms are similar to experiencing
gastroenteritis, severe infuenza, anxiety, and
dysphoria concurrently.
Severity of withdrawal can indicate a patient’s
level of physical dependence and can inform
medication choices and dosing decisions. The
duration of withdrawal depends on the specifc
opioid from which the patient is withdrawing and
Early withdrawal
Short-acting opioids:
8–24 hours after last
use
Long-acting opioids:
Up to 36 hours after
last use
Grade
1
Lacrimation,
rhinorrhea, or
both
Diaphoresis
Yawning
Restlessness
Insomnia
Early withdrawal Grade Dilated pupils
Short-acting opioids: 2 Piloerection
8–24 hours after last Muscle
use twitching
Long-acting opioids:
Up to 36 hours after
last use
Myalgia
Arthralgia
Abdominal pain
Fully developed Grade Tachycardia
withdrawal 3 Hypertension
Short-acting opioids: Tachypnea
1–3 days after last use Fever
Long-acting opioids: Anorexia or
72–96 hours after last
use
nausea
Extreme
restlessness
Fully developed Grade Diarrhea,
withdrawal 4 vomiting, or
Short-acting opioids: both
1–3 days after last use Dehydration
Long-acting opioids:
72–96 hours after last
Hyperglycemia
Hypotension
Curled-up use position
Total duration of withdrawal:
• Short-acting opioids: 7–10 days
• Long-acting opioids: 14 days or more
can last 1 to 4 weeks. After the initial withdrawal
phase is complete, many patients experience a
prolonged phase of dysphoria, craving, insomnia,
and hyperalgesia that can last for weeks or months.
Assess opioid withdrawal in the physical exam
by noting physical signs and symptoms (Exhibit
2.10). Structured measures (e.g., Clinical Opiate
Withdrawal Scale [COWS]; Clinical Institute
2-13
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Narcotic Assessment Scale for Withdrawal
Symptoms) can help standardize documentation
of signs and symptoms to support diagnosis,
initial management, and treatment planning. See
the “Resources” section for links to standardized
scales. Part 3 of this TIP covers withdrawal
symptom documentation for medication
initiation.
−
−
−
Abscesses or cellulitis.
The physical signs of opioid misuse vary
depending on the route of ingestion:
• Patients who primarily smoke or sniff
(“snort”) opioids or take them orally often
have few physical signs of use other than
signs of intoxication and withdrawal.
However, snorting can cause congestion
and damage nasal mucosa.
• Patients who inject opioids may develop:
− Sclerosis or scarring of the veins and
needle marks, or “track marks,” in the
arms, legs, hands, neck, or feet
(intravenous use).
− Edema in the foot, hand, or both
(common in injection use, but may occur
in oral use).
Jaundice, caput medusa, palmar erythema,
spider angiomata, or an enlarged or
hardened liver secondary to liver disease.
Heart murmur secondary to endocarditis.
Obtain Appropriate Laboratory Tests
Urine or oral fuid drug testing
Urine or oral fuid drug testing is useful before
initiating OUD medication. Testing establishes
a baseline of substances the patient has used
so that the provider can monitor the patient’s
response to treatment over time. Testing for
a range of commonly used substances helps
confrm patient histories, facilitates discussion
of recent drug use and symptoms, and aids in
diagnosing and determining severity of SUDs.
Drug testing is an important tool in the diagnosis
and treatment of addiction.
During ongoing medication for OUD
with buprenorphine or methadone,
drug testing can confrm medication
adherence.
EXHIBIT 2.11. Patient–Provider Dialog: Talking About Drug Testing
Frame drug testing in a clinical, nonpunitive way. For example, before obtaining a drug test, ask the
patient, “What do you think we’ll fnd on this test?” The patient’s response is often quite informative and
may make the patient less defensive than confrontation with a positive test result.
SCENARIO: A provider discusses urine drug testing with a patient being assessed for OUD treatment with
medication.
Provider: When we assess patients for medication for opioid addiction, we always check urine samples
for drugs.
Patient: I’ll tell you if I used. You don’t need to test me.
Provider: Thank you, I really appreciate that. The more we can talk about what’s going on with you, the
more I can help. I’m not checking the urine to catch you or because I don’t trust you. I trust
you. I can see how motivated you are. But I don’t trust the addiction because I know how
powerful addiction can be, too. To monitor your safety on medication and help determine
what other services you may need, it’s important for us to test you periodically and discuss
the results. Does that sound okay?
Patient: Yeah, that makes sense.
2-14
Medications for Opioid Use Disorder TIP 63
A national guideline on the use of drug testing
is available from ASAM.60 Exhibit 2.11 provides
guidance on talking with patients about drug
testing.
To assess and manage patients with OUD
properly, providers must know which tests to
order and how to interpret results. There are
many drug testing panels; cutoffs for positive
results vary by laboratory. One widely used
panel, the NIDA-5, tests for cannabinoids,
cocaine, amphetamines, opiates, and phencycli-
dine. Additional testing for benzodiazepines, the
broader category of opioids, and specifc drugs
commonly used in the patient’s locality may be
warranted. The typical opioid immunoassay will
only detect morphine, which is a metabolite
of heroin, codeine, and some other opioids.
The typical screen will not detect methadone,
buprenorphine, or fentanyl and may not detect
hydrocodone, hydromorphone, or oxycodone.
Specifc testing is needed to identify these
substances.
Co-occurring SUDs require separate,
specifc treatment plans.
Testing for substances that can complicate
OUD medication is essential. Testing for
cocaine, benzodiazepines, and methamphet-
amine is clinically important because these and
other substances (and related SUDs, which may
require treatment in their own right), especially
benzodiazepines, can complicate medication
treatment for OUD. Benzodiazepine and other
sedative misuse can increase the risk of overdose
among patients treated with opioid agonists.
When assessing benzodiazepine use, note that
typical benzodiazepine urine immunoassays will
detect diazepam but perhaps not lorazepam or
clonazepam. Providers must specifcally request
testing for these two benzodiazepines. Exhibit
2.12 shows urine drug testing windows of
detection.
EXHIBIT 2.12. Urine Drug Testing Window of Detection61,62
DRUG POSITIVE TEST
WINDOW OF
DETECTION* COMMENTS
Amphetamine;
methamphetamine;
3,4-methylenedioxy-
methamphetamine
Amphetamine 1–2 days False positives with bupropion,
chlorpromazine, desipramine, fuoxetine,
labetalol, promethazine, ranitidine,
pseudoephedrine, trazadone, and
other common medications. Confrm
unexpected positive results with the
laboratory.
Barbiturates Barbiturates Up to 6 weeks N/A
Benzodiazepines Benzodiazepines 1–3 days; up to 6
weeks with heavy
use of long-acting
benzodiazepines
Immunoassays may not be sensitive
to therapeutic doses, and most
immunoassays have low sensitivity to
clonazepam and lorazepam. Check with
your laboratory regarding sensitivity and
cutoffs. False positives with sertraline or
oxaprozin.
*Detection time may vary depending on the cutoff.
Continued on next page
2-15
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.12. Urine Drug Testing Window of Detection (continued)
DRUG POSITIVE TEST
WINDOW OF
DETECTION* COMMENTS
Buprenorphine Buprenorphine 3–4 days Will screen negative on opiate screen.
Tramadol can cause false positives. Can be
tested for specifcally.
Cocaine Cocaine,
benzoylecgonine
2–4 days; 10–22
days with heavy
use
N/A
Codeine Morphine,
codeine,
high-dose
hydrocodone
1–2 days Will screen positive on opiate
immunoassay.
Fentanyl Fentanyl 1–2 days Will screen negative on opiate screen. Can
be tested for specifcally. May not detect all
fentanyl-like substances.63
Heroin Morphine,
codeine
1–2 days Will screen positive on opiate
immunoassay. 6-monoacetylmorphine, a
unique metabolite of heroin, is present in
urine for about 6 hours. Can be tested for
specifcally to distinguish morphine from
heroin, but this is rarely clinically useful.
Hydrocodone Hydrocodone,
hydromorphone
2 days May screen negative on opiate
immunoassay. Can be tested for
specifcally.
Hydromorphone May not be
detected
1–2 days May screen negative on opiate
immunoassay. Can be tested for
specifcally.
Marijuana Tetrahydrocan-
nabinol
Infrequent
use of 1–3 days;
chronic use of
up to 30 days
False positives possible with efavirenz,
ibuprofen, and pantoprazole.
Methadone Methadone 2–11 days Will screen negative on opiate screen. Can
be tested for specifcally.
Morphine Morphine,
hydromorphone
1–2 days Will screen positive on opiate
immunoassay. Ingestion of poppy plant/
seed may screen positive.
Oxycodone Oxymorphone 1–1.5 days Typically screens negative on opiate
immunoassay. Can be tested for
specifcally.
*Detection time may vary depending on the cutoff.
2-16
Medications for Opioid Use Disorder TIP 63
Positive opioid tests can confrm recent
use. Document recent use before starting
patients on buprenorphine or methadone.
Positive methadone or buprenorphine tests are
expected for patients receiving these treatments.
Positive opioid tests contraindicate starting
naltrexone.
Negative opioid test results require careful
interpretation. A patient may test negative
for opioids despite presenting with opioid
withdrawal symptoms if he or she hasn’t used
opioids for several days. A negative opioid test
in the absence of symptoms of opioid withdrawal
likely indicates that the patient has little or no
opioid tolerance, which is important information
for assessment and treatment planning. Consider
that the opioid the patient reports using may not
be detected on the particular immunoassay.
Screening tests are not defnitive; false positive
and false negative test results are possible.
Confrmatory testing should follow all unexpected
positive screens. Urine drug testing will detect
metabolites from many prescription opioids but
miss others, so it is easy to misinterpret results in
patients taking these medications.64 False positives
are also common in amphetamine testing.65
Point-of-service testing provides the opportu-
nity to discuss results with patients immedi-
ately. However, cutoffs for positive screens are
not standardized across point-of-service tests.
Know the specifcations of the screens used.66
Other laboratory tests
Patients with OUD, particularly those who
inject drugs, are at risk for liver disease and
blood-borne viral infections. Pregnancy is
another important consideration in determining
treatment course. Recommended laboratory
tests for patients with OUD include:
Pregnancy testing, which is important because:
• It is not advisable for patients to start naltrex-
one during pregnancy.
• Pregnant women treated for active OUD
typically receive buprenorphine or methadone.
• The American College of Obstetricians
and Gynecologists and a recent SAMHSA-
convened expert panel on the treatment
of OUD in pregnancy67 recommend that
pregnant women with OUD receive opioid
receptor agonist medication.68
• Providers should refer pregnant women
to prenatal care or, if qualifed, provide it
themselves.
Liver function tests (e.g., aspartate aminotransfer-
ase, alanine aminotransferase, bilirubin), which can:
• Guide medication selection and dosing.
• Rule out severe liver disease, which may
contraindicate OUD medication (see Part 3
of this TIP).
Hepatitis B and C serology, which can indicate:
• Patients with positive tests (evaluate for
hepatitis treatment).
• The need to administer hepatitis A and B and
tetanus vaccines, if appropriate.
HIV serology, which can help identify:
• Patients who are HIV positive (evaluate for
antiretroviral treatment).
• Patients who are HIV negative (evaluate
for preexposure prophylaxis and targeted
education).
Review the PDMP
Before initiating OUD medication, providers
should check their states’ PDMPs to
determine whether their patients receive
prescriptions for controlled substances
from other healthcare professionals. Using
the PDMP improves the ability to manage the
risks of controlled substances and to identify
potentially harmful drug interactions.69 Although
OTPs are not permitted to report methadone
treatment to PDMPs, pharmacies that dispense
buprenorphine and other controlled substances
do report to PDMPs. Medications that need
monitoring and required frequency of updates
vary by state (for more information about state
PDMPs, visit www.pdmpassist.org/content
/state-profles).
2-17
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Determine Diagnosis and Severity of OUD
Use DSM-5 criteria to make an OUD diagnosis
(Exhibit 2.13).70 Patients who meet two or three
criteria have mild OUD. Those meeting four
or fve criteria have moderate OUD, and those
meeting six or more criteria have severe OUD.71
A printable checklist of DSM-572 criteria is
available in the Part 2 Appendix.
Treatment Planning or Referral
Making Decisions About Treatment
Start by sharing the diagnosis with patients
and hearing their feedback. Patients with
OUD need to make several important
treatment decisions:
• Whether to begin medication to treat OUD.
• What type of OUD medication to take.
RESOURCE ALERT
EXHIBIT 2.13. DSM-5 Criteria for OUD73
A problematic pattern of opioid use leading to clinically signifcant impairment or distress, as manifested
by at least two of the following, occurring within a 12-month period:
1. Opioids are often taken in larger amounts or over a longer period of time than was intended.
2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
3. A great deal of time is spent in activities to obtain the opioid, use the opioid, or recover from its effects.
4. Craving, or a strong desire or urge to use opioids.
5. Recurrent opioid use resulting in a failure to fulfll major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused
by or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
8. Recurrent opioid use in situations in which it is physically hazardous.
9. Continued opioid use despite knowledge of having a persistent or recurrent physical or
psychological problem that’s likely to have been caused or exacerbated by the substance.
10. Tolerance,* as defned by either of the following:
a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect
b. A markedly diminished effect with continued use of the same amount of an opioid
11. Withdrawal,* as manifested by either of the following:
a. The characteristic opioid withdrawal syndrome
b. The same—or a closely related—substance is taken to relieve or avoid withdrawal symptoms
*This criterion is not met for individuals taking opioids solely under appropriate medical supervision.
Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms
Shared Decision-Making Resources
for Patients and Family Members
SAMHSA’s shared decision-making resource
page is a good information source for patients
to review before their visit or in the office
(www.samhsa.gov/brss-tacs/recovery-support-
tools/shared-decision-making). In addition,
providers can suggest that family, friends,
and other potential recovery supports (e.g.,
12-Step program sponsors, employers, clergy)
read educational material tailored for them.
See Medication-Assisted Treatment for Opioid
Addiction: Facts for Families and Friends
(https://portal.ct.gov/-/media/DMHAS/Opioid-
Resources/MATInfoFamilyFriendspdf.pdf).
2-18
Medications for Opioid Use Disorder TIP 63
• Where and how to access desired treatment.
• Whether to access potentially benefcial
mental health, recovery support, and other
ancillary services, whether or not they choose
medication for OUD.
Offer information to patients about the
various treatments for OUD and collaborate
with them to make decisions about treatment
plans or referrals (Exhibit 2.14). Consider
discussing:
• Indications, risks, and benefts of medications
and alternatives to medication for OUD.
• Types of settings that deliver medications
(including healthcare professionals’ own
practice locations, if applicable).
• Availability of and accessibility to treatment
(i.e., transportation).
• Alternative treatments without medication
(e.g., residential treatment, which often offers
medically supervised opioid withdrawal).
• Costs of treatment with OUD medication,
including insurance coverage and affordability.
Give patients’ expressed preferences signif-
icant weight when making decisions. Patient
characteristics can’t reliably predict greater likeli-
hood of success with one approved medication or
another. For detailed information on medications
to treat OUD, refer to Part 3 of this TIP.
Strategies to engage patients in shared
decision making include:
• Indicating to patients a desire to collaborate
with them to fnd the best medication and
treatment setting for them.
• Including family members in the treatment
planning process, if possible (and only with
patients’ consent).
• Exploring what patients already know
about treatment options and dispelling
misconceptions.
• Offering information on medications and their
side effects, benefts, and risks (Exhibit 2.14;
Part 3).
Part 1 of this TIP gives an overview of
the three FDA-approved medications
used to treat OUD. Part 3 covers the
details of their use.
• Informing patients of the requirements of the
various treatment options (e.g., admission
criteria to an OTP; frequency of visits to an
OBOT or OTP).
• Offering options, giving recommendations
after deliberation, and supporting patients’
informed decisions.
Understanding Treatment Settings and
Services
Support patient preferences for treatment
settings and services. Some patients prefer to
receive OUD medication via physicians’ offces.
Others choose outpatient treatment programs
that provide opioid receptor agonist treatment
for medically supervised withdrawal (with or
without naltrexone) or for ongoing opioid
receptor agonist maintenance treatment. Still
others may want OUD treatment in a residential
program with or without medication (Exhibit
2.15).
Many patients initially form a preference for a
certain treatment without knowing all the risks,
benefts, and alternatives. Providers should
ensure that patients understand the risks and
benefts of all options. Without this understand-
ing, patients can’t give truly informed consent.
Outpatient OUD Treatment Settings
Refer patients who prefer treatment with
methadone or buprenorphine via an OTP and
explain that:
• They will have to visit the program from 6 to 7
times per week at frst.
• Additional methadone take-home doses are
possible at every 90 days of demonstrated
progress in treatment.
• Buprenorphine take-home doses are not
bound by the same limits as methadone.
2-19
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.14. Comparison of OUD Medications To Guide Shared
Decision Making
CATEGORY BUPRENORPHINE METHADONE NALTREXONE
Appropriate Typically for patients with Typically for patients Typically for patients with
patients OUD who are physiologically
dependent on opioids
with OUD who are
physiologically dependent
on opioids and who meet
federal criteria for OTP
admission
OUD who are abstinent
from short-acting opioids
for 7 days and long-acting
opioids for 10–14 days
Outcome: Higher than treatment Higher than treatment Treatment retention with
Retention in without medication and without OUD medication oral naltrexone is no better
treatment treatment with placebo74 and treatment with
placebo75
than with placebo or no
medication;76 for XR-NTX,
treatment retention is
higher than for treatment
without OUD medication
and treatment with
placebo77,78
Outcome:
Suppression of
illicit opioid use
Effective Effective Effective
Outcome:
Overdose
mortality
Lower for people in treatment
than for those not in it
Lower for people in
treatment than for
those not in it
Unknown
Location/ Offce/clinic: Begins daily OTP only: 6–7 days/week Offce/clinic: Varies from
frequency of to weekly, then tailored to initially; take-homes are weekly to monthly
offce visits patient’s needs
OTP: Can treat with
buprenorphine 6–7 days/
week initially; take-homes are
allowed without the time-in-
treatment requirements of
methadone
allowed based on time
in treatment and patient
progress
Who can Physicians, NPs,* PAs, and, OTP physicians order the Physicians, NPs,* PAs,
prescribe/ until October 1, 2023, clinical medication; nurses and and, until October 1, 2023,
order? nurse specialists, certifed
registered nurse anesthetists,
and certifed nurse midwives
possessing a federal waiver
can prescribe and dispense;
also can be dispensed by a
community pharmacy or an
OTP
pharmacists administer
and dispense it
clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed
nurse midwives
*NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives should check
with their state to determine whether prescribing buprenorphine, naltrexone, or both is within their allowable scope
of practice.
Continued on next page
2-20
Medications for Opioid Use Disorder TIP 63
EXHIBIT 2.14. Comparison of OUD Medications To Guide Shared
Decision Making (continued)
CATEGORY BUPRENORPHINE METHADONE NALTREXONE
Administration Sublingual/buccal; injection;
implant by specially trained
provider, and only for
stabilized patients
Oral Oral or intramuscular
(Note: Oral naltrexone
is less effective than the
other OUD medications.)
Misuse/diver- Low in OTPs or other Low in OTPs with directly None
sion potential settings with observed dose
administration; moderate for
take-home doses; risk can be
mitigated by providing take-
homes to stable patients
only and having a diversion
control plan for the practice
or program. Appropriate
patients may be transitioned
to a depot formulation of
buprenorphine if and when
it is appropriate.
observed therapy;
moderate for take-
home doses; risk can be
mitigated by a diversion
control plan
Sedation Low unless concurrent
substances are present (e.g.,
alcohol, benzodiazepines)
Low unless dose titration
is too quick or dose is
not adjusted for the
presence of concurrent
substances (e.g., alcohol,
benzodiazepines)
None
Risk of
medication-
induced respira-
tory depression
Very rare; lower than
methadone
Rare, although higher than
buprenorphine; may be
elevated during the frst 2
weeks of treatment or in
combination with other
sedating substances
None
Risk of Can occur if started too None Severe withdrawal is
precipitated prematurely after recent use possible if period of
withdrawal of other opioids abstinence is inadequate
when starting before starting medication
medication
Withdrawal
symptoms on
discontinuation
Present; lower than
methadone if abruptly
discontinued
Present; higher than
buprenorphine if abruptly
discontinued
None
Most common Constipation, vomiting, Constipation, vomiting, Diffculty sleeping, anxiety,
side effects headache, sweating,
insomnia, blurred vision
sweating, dizziness,
sedation
nausea, vomiting, low
energy, joint and muscle
pain, headache, liver
enzyme elevation
XR-NTX: Injection site pain,
nasopharyngitis, insomnia,
toothache
D. Coffa, December 2017 (personal communication). Adapted with permission.
2-21
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.15. Treatment Setting
Based on Patient’s Choice of
OUD Medication
MEDICATION
POSSIBLE TREATMENT
SETTING
Buprenorphine Offce-based treatment,
outpatient or residential
SUD treatment programs
(prescriber must have a
federal waiver), OTP. REMS
program participation is
required for use of depot
formulations.
Methadone OTP
Naltrexone Offce-based treatment,
outpatient or residential
SUD treatment programs,
OTP
• Counseling and drug testing are required
parts of OTP treatment.
• Some programs also offer case management,
peer support, medical services, mental
disorder treatment, and other services.
Try to arrange OTP intake appointments for
patients before they leave the offce. If no
immediate openings are available, consider
starting buprenorphine as a bridge or alternative
to the OTP.
Gauge the appropriate intensity level
for patients seeking non-OTP outpatient
treatment for OUD. These programs range
from low intensity (individual or group counseling
once to a few times a week) to high intensity
(2 or more hours a day of individual and group
counseling several days a week). Appropriate
treatment intensity depends on each patient’s:79
• Social circumstances.
• Severity of addiction.
• Personal preferences.
• Psychiatric/psychological needs.
• Ability to afford treatment at a given intensity.
Outpatient medical settings
Healthcare professionals cannot provide
methadone in their clinics. Only those with
a buprenorphine waiver can provide buprenor-
phine. Any healthcare professional with a pre-
scribing authority can provide naltrexone.
Once providers obtain the necessary waiver,
they should offer buprenorphine treatment
to all patients who present with OUD if such
treatment is available and appropriate. Referring
them to treatment elsewhere will likely result in
delay or lack of patient access to care. Develop
a treatment plan to determine where patients
will receive continuing care (see the “Treatment
Planning” section). Continue to provide nal-
trexone for patients who were already receiving
it from some other setting (e.g., a prison, a
specialty addiction treatment program) or for
patients who meet opioid abstinence require-
ments and wish to take a medication for relapse
prevention.
Residential drug treatment settings
Patients who have OUD, concurrent other
substance use problems, unstable living
situations, or a combination of the three may
be appropriate candidates for residential
treatment, which can last from a week to
several weeks or more. Inform patients about
the services and requirements typical of this
treatment setting.
Some patients taking buprenorphine (or
methadone) who have other SUDs, such as
AUD or cocaine use disorder, can beneft
from residential treatment. If such treatment
is indicated, determine whether the residential
program allows patients to continue their opioid
receptor agonist medication while in treatment.
Some residential programs require patients
to discontinue these medications to receive
residential treatment, which could destabilize
patients and result in opioid overdose.
2-22
Medications for Opioid Use Disorder TIP 63
•
•
•
Residential treatment programs typically
provide:
• Room and board.
• Recovery support.
• Counseling.
• Case management.
• Medically supervised withdrawal (in some
programs).
• Starting buprenorphine or naltrexone (in some
programs).
• Onsite mental health services (in some cases).
• Buprenorphine or methadone continuation for
patients already enrolled in treatment prior
to admission if their healthcare professionals
have waivers or their OTP permits.
Transitioning out of residential settings
requires careful planning. During a patient’s
stay in residential treatment, plan for his or her
transition out of the program. A good transition
plan maximizes the likelihood of continuity of
care after discharge. Plans should also address
overdose risk. Patients who are no longer
RESOURCE ALERT
Treatment and Provider Locator
SAMHSA’s Behavioral Health Treatment
Services Locator (https://fndtreatment.samhsa
.gov) provides information on drug and alcohol
treatment programs across states. Another
SAMHSA tool identifes the locations of
buprenorphine providers (www.samhsa.gov
/medication-assisted-treatment/physician
-program-data/treatment-physician-locator).
opioid tolerant are at heightened risk of opioid
overdose if they don’t get OUD medication at
discharge. Providing XR-NTX, buprenorphine,
or methadone during treatment and continuing
the medication after discharge can help prevent
return to opioid use after discharge. Providing a
naloxone prescription and overdose prevention
information is appropriate.
RESOURCE ALERT
Maintaining Confdentiality
Providers who treat patients with addiction
must know substance use-related disclosure
rules and confdentiality requirements. SAMHSA’s
webpage lists frequently asked questions on
substance use confdentiality and summarizes
federal regulations about disclosure and patient
records that federal programs maintain on
addiction treatment (www.samhsa.gov/about-us/
who-we-are/laws-regulations/confdentiality-
regulations-faqs). Key points include:
Confdentiality regulations prohibit specialty
SUD treatment programs from sharing
information with healthcare professionals
about patients’ SUD treatment without specifc
consent from patients.
Referrals to other behavioral health services
require consent for sharing information on
treatment progress.
Healthcare professionals should discuss
confdentiality and consent with patients
during the referral process.
• OUD medication prescribers may consider
requiring patient consent for communicating
with treatment programs as a condition of
receiving OUD treatment.
Treatment program staff members can help
identify returns to substance use, or risk of such,
before the prescriber and can work with the
prescriber to stabilize patients.
2-23
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Determining OUD Service Intensity and
Ensuring Follow-Through
Use ASAM placement criteria for guidance on
selecting the right level of OUD treatment.
ASAM criteria defne the level of care and key
features that may make a given level (e.g.,
residential, intensive outpatient, standard
outpatient) appropriate for a patient80 (see
the “Treatment Planning” section). To help
patients select programs, note that some focus
on specifc populations (e.g., gender-specifc
programs; parents with children; lesbian,
gay, bisexual, transgender, and questioning
populations).
Make an appointment with the referral
program during the patient’s visit rather than
giving the patient a phone number to call.
Follow up with the patient later to determine
whether he or she kept the appointment. Doing
so increases the chances of a successful referral.
Referring patients to behavioral health and
support services
Discuss patients’ potential need for behavioral
health, peer support, and other ancillary
services, like:
• Drug and alcohol counseling.
• Mental health services.
• Case management.
• Mutual-help groups.
• Peer recovery support services.
Offer referrals to counseling and tailored
psychosocial support to patients receiving
OUD medication (Exhibit 2.16).
Drug Addiction Treatment Act of 2000
legislation requires that buprenorphine pre-
scribers be able to refer patients to counseling,
but making referrals is not mandatory.81 Many
patients beneft from referral to mental health
services or specialized addiction counseling and
recovery support services. However, four ran-
domized trials found no extra beneft to adding
adjunctive counseling to well-conducted medical
RESOURCE ALERT
Mutual-Support Groups
For an introduction to mutual-support groups,
see SAMHSA’s Substance Abuse in Brief,
“An Introduction to Mutual Support Groups
for Alcohol and Drug Abuse” (http://www.
williamwhitepapers.com/pr/CSAT%20
Mutual%20Support%20Groups%202008.pdf).
management visits delivered by the buprenor-
phine prescriber. There is evidence of benefts to
adding contingency management to medication
for OUD.82,83,84,85,86
Make referrals to mutual-help groups.
Patients may wish to participate in mutual-
help groups (e.g., Alcoholics Anonymous,
Narcotics Anonymous, Methadone Anonymous,
Medication-Assisted Recovery Services, SMART
Recovery) in addition to or instead of specialized
treatment. These programs can be highly
supportive, but they may pressure patients to
stop taking OUD medication. If possible, refer
patients to groups that welcome patients who
take OUD medication.
Make referrals to medical and mental health
services. Respectful, consistent medical care can
support patients’ efforts to recover from OUD
and all other SUDs. As for any patient, providers
should make appropriate referrals for patients
with OUD to receive medical or mental health
services beyond the providers’ own scope of
practice.
Patients with depression, anxiety disorders, and
other mental disorders may be more likely to
succeed in addiction treatment if those condi-
tions are managed.87 If the severity or type of
a patient’s psychiatric comorbidity is beyond a
provider’s scope of practice, the provider should
refer the patient to mental health services as
appropriate.
2-24
Medications for Opioid Use Disorder TIP 63
EXHIBIT 2.16. Referring Patients Who Receive OUD Medications to
Behavioral Health Therapies
Case
management
Vocational
training
Yes No
Yes No
Is the patient
willing to engage
in additional
behavioral health
therapies?
Is the patient
entering an OTP
for methadone or
intensive treatment?
Offer best advice and
ongoing motivational
interviewing; revisit
offer for behavioral
health therapies.
Counseling, peer
support, and case
management will
likely be provided
through the OTP.
Identify specifc
needs, and refer
appropriately to
one or more of
the following:
Counseling:
Individual, family,
and/or group
Peer support groups:
Alcoholics Anonymous,
Narcotics Anonymous,
SMART Recovery,
buprenorphine groups
Housing,
transportation,
food, legal, and other
support programs
RESOURCE ALERT
Guidance on Providing Integrated Care
Fragmented healthcare services are less likely to
meet all patient needs. Integrated medical and
behavioral healthcare delivery can effectively
provide patient-focused, comprehensive treat-
ments that address the full range of symptoms and
service needs patients with OUD often have.88 The
key components of integration should be in place
to make sure that SUD treatment in a primary
care setting works. For more information about
how to provide integrated services for individuals
taking medication for OUD, see:
• The Agency for Healthcare Research and
Quality’s report Medication-Assisted Treatment
Models of Care for Opioid Use Disorder in
Primary Care Settings (www.ncbi.nlm.nih.gov/
books/NBK402352).
• The Agency for Healthcare Research and
Quality’s Academy for Integrating Behavioral
Health and Primary Care (https://
integrationacademy.ahrq.gov).
2-25
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
OPPORTUNITY ALERT
Becoming an OUD Medication Treatment Provider
SAMHSA strongly urges
physicians, NPs, PAs, and,
until October 1, 2023, clinical
nurse specialists, certifed
registered nurse anesthetists,
and certifed nurse midwives
to obtain waivers that
will qualify them to offer
buprenorphine treatment.
They can become qualifed to
use buprenorphine to taper
appropriate patients with OUD
off illicit or prescription opioids
or to provide long-term OUD
treatment.
Only healthcare professionals
with a federal waiver may
prescribe buprenorphine for
the treatment of OUD. There
are two pathways by which
providers can obtain waivers.
In the traditional pathway,
providers must meet set criteria,
complete buprenorphine
training (online or in person),
and apply for a waiver from
SAMHSA by submitting a notice
of intent (NOI). An alternate
pathway was established
in April 2021 under which
healthcare professionals who
are state licensed and possess
a valid DEA registration may
be exempted from the training
requirement, as well as the
required attestation about
providing patients with access
to or referrals for psychosocial
services if they wish to treat
up to 30 patients only. This
exemption applies not just
to physicians but to NPs,
PAs, clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed nurse
midwives as well. Providers
applying under this exemption
must still submit an NOI, and
time spent practicing under
this exemption does not qualify
the provider for subsequent
increases in their patient cap.89
If after 1 year providers wish to
treat more than 30 patients,
they must submit an NOI
using the traditional pathway.
Regardless of which method is
used to submit an NOI, waivered
prescribers are assigned an
additional DEA registration
number (usually their existing
number with an added “X”).90
NPs, PAs, clinical nurse
specialists, certifed registered
nurse anesthetists, and
certifed nurse midwives need
to meet additional criteria for
waivers.91 These providers who
are state licensed and possess
a valid DEA registration may be
exempted from training and
psychosocial services attestation
requirements and may instead
apply for a waiver by submitting
an NOI.92 Providers can still
apply for the traditional NOI if
they wish to apply for increases
in their patient cap after 1 year.
Check with the state licensing
board about restrictions and
requirements at the state level
before applying for a waiver.
Wavier training: ASAM, the
American Academy of Addiction
Psychiatry, the American
Psychiatric Association, and the
American Osteopathic Academy
of Addiction Medicine all provide
the waiver training courses for
physicians. Providers’ Clinical
Support System for Medication
Assisted Treatment (PCSS-
MAT) provides the required
8-hour OUD medication waiver
course for physicians and 24-
hour waiver course for NPs,
PAs, clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed
nurse midwives for free (https://
pcssnow.org/medication-
assisted-treatment/). Other
providers also provide NP, PA,
clinical nurse specialist, certifed
registered nurse anesthetist,
and certifed nurse midwife
courses.
Providers who are state licensed
and DEA registered may submit
an NOI in lieu of these training
requirements as well as the
required attestation about
providing patients access to
or referrals for psychosocial
services. Providers practicing
under this exemption are
limited to treating no more
than 30 patients at a time,
however. Learn more by reading
SAMHSA’s “FAQs About the
New Buprenorphine Practice
Guidelines” at www.samhsa.gov/
medication-assisted-treatment/
practitioner-resources/faqs.
New prescribers can beneft
from mentorship from
experienced providers in
their practice or community.
Mentorship is available for free
from PCSS-MAT (http://pcssmat
.org/mentoring).
For detailed information on
prescribing OUD medications,
review Part 3 of this TIP.
2-26
Medications for Opioid Use Disorder TIP 63
Make referrals to ancillary services. Besides
medical care and mental health services, OUD
patients, like patients with other illnesses, may
need more support in some areas, including
ancillary services such as:
• Case management.
• Food access.
• Vocational training.
• Housing.
• Transportation.
• Legal assistance.
Helping patients who are not ready to
engage in OUD treatment
Help reluctant patients be safer and approach
readiness. Patients may seem unwilling to discuss
their drug use if they’re ashamed or fear being
judged. Accepting, nonjudgmental attitudes help
patients overcome shame and discuss concerns
honestly while also instilling hope.
Every visit is a chance to help patients begin
healthy changes and move toward treatment
and recovery. Patients may not be ready to
change right away. Successfully quitting drug use
can take many attempts. Returns to substance
use, even after periods of remission, are
expected parts of the recovery process.
Patients with OUD are much more likely to
die than their peers,93,94 and HIV, hepatitis C,
and skin and soft tissue infections are common
among this population. Help reduce these OUD-
related risks by testing patients for HIV and
hepatitis and by educating patients about:
• Using new syringes.
• Avoiding syringe sharing.
• Avoiding sharing other supplies during the
injection process.
• Preventing opioid overdose (see the
“Preventing Opioid-Related Overdose” section).
• Obtaining overdose prevention infor-
mation and resources (e.g., SAMHSA
Opioid Overdose Prevention Toolkit
[https://store.samhsa.gov/product/
Opioid-Overdose-Prevention-Toolkit/
SMA18-4742]).
• Obtaining naloxone and instructions for its use.
Refer patients to syringe exchange sites.
The North American Syringe Exchange Network
provides options (see the “Syringe Exchange”
section).
Preventing Opioid-Related Overdose
Every patient who misuses opioids or has
OUD should receive opioid overdose preven-
tion education and a naloxone prescription.95
Healthcare professionals should educate
patients and their families about overdose risk,
prevention, identifcation, and response (Exhibit
2.17). FDA has approved an autoinjectable
naloxone device (Evzio) and a naloxone nasal
spray (Narcan) for use by patients and others.
For information about all forms of naloxone,
prescribing, and patient and community
education, see the SAMHSA Opioid Overdose
Prevention Toolkit (https://store.samhsa.gov/
product/Opioid-Overdose-Prevention-Toolkit/
SMA18-4742).
2-27
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
EXHIBIT 2.17. Opioid Overdose: Risk, Prevention, Identifcation,
and Response
Overdose risk
• Using heroin (possibly mixed with illicitly
manufactured fentanyl or fentanyl analogs)
• Using prescription opioids that were not
prescribed
• Using prescription opioids more frequently or
at higher doses than prescribed
• Using opioids after a period of abstinence or
reduced use (e.g., after medically supervised
withdrawal or incarceration)
• Using opioids with alcohol, benzodiazepines,
or both
Overdose prevention
• Don’t use opioids that were not prescribed.
• Take medications only as prescribed.
• Don’t use drugs when you are alone.
• Don’t use multiple substances at once.
• Have naloxone available and make sure others
know where it is and how to use it.
• Use a small “test dose” if returning to opioid use
after a period of abstinence, if the substance
appears altered, or if it has been acquired from
an unfamiliar source. Beware: This doesn’t
guarantee safety; illicitly manufactured fentanyl
or other substances may be present in the drug,
and any use may be fatal.
The United States is experiencing an
epidemic of opioid overdose deaths.
Opioids (including prescription opioids
and heroin) killed 49,860 people in 2019,
more than in any prior year. Less than
one-third of overdose deaths involved
prescription opioids.97 From 2010 to
2018, heroin-related overdose deaths
rose about fvefold.98,99 Overdose deaths
from illicit fentanyl have also risen
sharply.100
Overdose identifcation
• Fingernails or lips are blue or purple.
• Breathing or heartbeat is slow or stopped.
• The person is vomiting or making gurgling noises.
• The person can’t be awakened or is unable to
speak.
Overdose response
• Call 9-1-1.
• Administer naloxone (more than one dose may
be needed to restore adequate spontaneous
breathing).
• Perform rescue breathing. If certifed to provide
cardiopulmonary resuscitation, perform chest
compressions if there is no pulse.
• Put the person in the “recovery position,” on his
or her side and with the mouth facing to the
side to prevent aspiration of vomit, if he or she is
breathing independently.
• Stay with the person until emergency services
arrive. Naloxone’s duration of action is 30–90
minutes. The person should be observed
after this time for a return of opioid overdose
symptoms.
Adapted from material in the public domain.96
Municipalities with community-based naloxone
distribution programs have seen substantial
decreases in opioid overdose death rates.101,102
Many syringe exchange programs also dispense
naloxone. For information and resources on
prescribing naloxone for overdose prevention,
including educational patient handouts and
videos, see the “Opioid-Related Overdose
Prevention” section.
2-28
Medications for Opioid Use Disorder TIP 63
Resources
The following selected resources address key
content presented in Part 2. Part 5 of this TIP
includes comprehensive resources on topics
pertaining to substance misuse and medications
to treat OUD.
Alcohol and Drug Use Screening
• American Academy of Addiction
Psychiatry: Provides Performance in Practice
Clinical Modules for screening of tobacco
use and AUD. www.cvent.com/events/
aaap-pips/event-summary-9f3d326cf2a94a-
f49153a1834832534e.aspx
• NIAAA, Professional Education Materials:
Provides links to screening, treatment
planning, and general information for clinicians
in outpatient programs. www.niaaa.nih.gov
/publications/clinical-guides-and-manuals
• NIDA, Medical and Health Professionals:
Provides resources for providers to increase
awareness of the impact of substance use
on patients’ health and help identify drug
use early and prevent it from escalating to
misuse or addiction. www.drugabuse.gov
/nidamed-medical-health-professionals
Tobacco Screening
• American Psychiatric Nursing Association,
Tobacco & Nicotine Use Screening Tools
and Assessments: Provides the Fagerström
screening tools for nicotine dependence and
smokeless tobacco and a screening checklist
for tobacco use. www.apna.org/i4a/pages
/index.cfm?pageID=6150
• U.S. Department of Health and Human
Services’ Be Tobacco Free: Provides infor-
mation for individuals struggling with nicotine
addiction and links for clinicians that provide
guidance on caring for patients with nicotine
addiction. https://betobaccofree.hhs.gov/
• U.S. Department of Health and Human
Services’ Million Hearts Initiative: Provides
templates for developing and guidance on
implementing tobacco cessation programs
and guidance on implementing them as part
of clinical care. https://millionhearts.hhs.gov
/tools-protocols/protocols.html
• Centers for Disease Control and Prevention
(CDC): Offers resources and information for
patients and clinicians; includes a webpage
with resource links for clinicians on treating
tobacco dependence. www.cdc.gov/tobacco
/index.htm and www.cdc.gov/tobacco/basic
_information/related_links/index.htm
Buprenorphine Treatment Locator
• SAMHSA, Buprenorphine Treatment
Practitioner Locator: Provides a state-by-
state list of providers who offer buprenor-
phine. www.samhsa.gov/medication-assisted
-treatment/physician-program-data
/treatment-physician-locator
Buprenorphine Training, Mentorship,
and Waivers
• SAMHSA, Buprenorphine Waiver
Management: Provides information on
buprenorphine waivers with links to waiver
applications; explains waiver processes,
training and psychosocial service attestation
exemptions, requirements, and recordkeep-
ing. www.samhsa.gov/medication-assist-
ed-treatment/training-materials-resources/
apply-for-practitioner-waiver
• SAMHSA, Buprenorphine Practice
Guidelines: Provides information about
how and why providers might be exempt
from training and psychosocial service
attestation requirements for obtaining a
SAMHSA X waiver. www.federalregister.gov/
documents/2021/04/28/2021-08961/prac-
tice-guidelines-for-the-administration-of-bu-
prenorphine-for-treating-opioid-use-disorder
• SAMHSA, Buprenorphine Training for
Physicians: Provides links to organizations
that train physicians on buprenorphine
treatment. www.samhsa.gov/medication-as-
sisted-treatment/training-materials-resources/
apply-for-practitioner-waiver
2-29
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
• SAMHSA, Qualify for a Practitioner Waiver:
Provides information for NPs, PAs, clinical
nurse specialists, certifed registered nurse
anesthetists, and certifed nurse midwives
about the buprenorphine waiver training,
with links to trainings and the application
process. www.samhsa.gov/medication-assist-
ed-treatment/training-materials-resources/
apply-for-practitioner-waiver
• PCSS-MAT: Provides buprenorphine waiver
training and mentorship for healthcare pro-
fessionals (physicians, NPs, PAs, clinical nurse
specialists, certifed registered nurse anesthe-
tists, and certifed nurse midwives); includes
updates and other resources about medication
for OUD. https://pcssnow.org/
Medication Treatment for OUD
• SAMHSA, Advisory, Sublingual and
Transmucosal Buprenorphine for Opioid
Use Disorder: Review and Update:
Summarizes information on the use of
buprenorphine to treat OUD.
https://store.samhsa.gov/product/
Advisory-Sublingual-and-Transmucosal-
Buprenorphine-for-Opioid-Use-Disorder-/
SMA16-4938
• SAMHSA, Clinical Use of Extended-Release
Injectable Naltrexone in the Treatment
of Opioid Use Disorder: A Brief Guide:
Provides a brief review of the use of XR-NTX.
https://store.samhsa.gov/product/Clinical
-Use-of-Extended-Release-Injectable
-Naltrexone-in-the-Treatment-of-Opioid
-Use-Disorder-A-Brief-Guide/SMA14-4892R
• ASAM, The ASAM National Practice
Guideline for the Treatment of Opioid
Use Disorder. 2020 Focused Update:
Provides national practice guidelines
for the use of medications to treat OUD.
www.asam.org/docs/default-source/
quality-science/npg-jam-supplement.
pdf?sfvrsn=a00a52c2_2
• Department of Veterans Affairs/
Department of Defense, VA/DoD Clinical
Practice Guideline for the Management
of Substance Use Disorders: Provides
substance use disorder practice guidelines.
www.healthquality.va.gov/guidelines/MH/sud
/VADoDSUDCPGRevised22216.pdf
• PCSS-MAT: Provides training and mentorship
for healthcare professionals (physicians, NPs,
PAs, clinical nurse specialists, certifed regis-
tered nurse anesthetists, and certifed nurse
midwives) on medications for OUD treatment
including buprenorphine, naltrexone, and
methadone. https://pcssnow.org/
Syringe Exchange
• North American Syringe Exchange
Network: Provides a national directory of
syringe exchange programs in the United
States. https://nasen.org/directory
Opioid-Related Overdose Prevention
• Prescribe To Prevent: Provides information
about naloxone prescribing for overdose
prevention, including educational patient
handouts and videos. http://prescribeto
prevent.org
• SAMHSA Opioid Overdose Prevention
Toolkit: Provides healthcare professionals,
communities, and local governments
with material to develop practices and
policies to help prevent opioid-related
overdoses and deaths. It addresses issues
for healthcare professionals, frst responders,
treatment providers, and those recovering
from opioid overdose as well as their
families. https://store.samhsa.gov/product/
Opioid-Overdose-Prevention-Toolkit/
SMA18-4742
• CDC—Overdose Prevention: Provides links
and tools for clinicians to help prevent opioid
overdose deaths. www.cdc.gov/drugover-
dose/prevention/index.html
2-30
Medications for Opioid Use Disorder TIP 63
• NIDA, Opioid Overdose Reversal with
Naloxone (Narcan, Evzio): Provides naloxone
information for providers. www.drugabuse
.gov/related-topics/opioid-overdose
-reversal-naloxone-narcan-evzio
Opioid Withdrawal Scales
• WHO Guidelines for the Psychosocially
Assisted Pharmacological Treatment of
Opioid Dependence: Annex 10: Provides
COWS and other opioid withdrawal scales.
www.ncbi.nlm.nih.gov/books/NBK143183
• The Clinical Institute Narcotic Assessment
Scale for Withdrawal Symptoms: Provides
a scale that measures signs and symptoms
observed in patients during withdrawal. www
.ncpoep.org/wp-content/uploads/2015/02
/Appendix_7_Clinical_Institute_Narcotic
_Assessment_CINA_Scale_for_Withdrawal
_Symptoms.pdf
Patient and Family Education on
Medications To Treat OUD
• SAMHSA Store: Provides patient and family
educational resources about OUD and
medication treatment for OUD; some
resources are available in multiple languages,
including Spanish. https://store.samhsa.gov
− Buprenorphine. https://store.samhsa.gov
/product/The-Facts-about-Buprenorphine
-for-Treatment-of-Opioid-Addiction
/SMA15-4442
− Methadone. https://roar.nevadaprc.
org/system/documents/3100/original/
NPRC.168.WhatEveryIndividualNeeds
ToKnow.pdf?1435165554
• ASAM Resources: Provides patient and family
education tools about addiction in general
and OUD specifcally.
− Patient Resources. www.asam.org
/resources/patientresources
− Opioid Addiction Treatment: A Guide for
Patients, Families, and Friends. www.asam.
org/docs/default-source/publications/asam-
opioid-patient-piece_-5bopt2-5d_3d.pdf
Referral and Treatment Locators
• SAMHSA, OTP Directory: Provides a state-
by-state directory of methadone OTPs. https://
dpt2.samhsa.gov/treatment/directory.aspx
• SAMHSA, Behavioral Health Treatment
Services Locator: Provides a directory of
treatment facilities. https://fndtreatment
.samhsa.gov
• SAMHSA, Behavioral Health Treatment
Services Locator—Self-Help, Peer Support,
and Consumer Groups: Provides a directory
for mutual-help groups. https://fndtreatment.
samhsa.gov/
Screening, Assessment, and Drug Testing
Resources
• NIDA, Screening Tools and Prevention:
Provides an evidence-based screening
tool chart for adolescents and adults, drug
use screening tool support materials, and
a clinician resource and quick reference
guide for drug screening in general
medical settings, including the NIDA-
Modifed ASSIST (NM ASSIST). www.
drugabuse.gov/nidamed-medical-health-
professionals/tool-resources-your-practice/
additional-screening-resources
• ASAM, The ASAM Appropriate Use of Drug
Testing in Clinical Addiction Medicine:
Discusses appropriate use of drug testing in
identifying, diagnosing, and treating people
with or at risk for SUDs. www.asam.org/
Quality-Science/quality/drug-testing
• USPSTF, Final Recommendation
Statement—Unhealthy Drug Use: Screening
Discusses updated recommendations about
screening for illicit drug use and prescription
medication misuse in adults in primary
care settings. https://uspreventiveser-
vicestaskforce.org/uspstf/recommendation/
drug-use-illicit-screening
2-31
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Treatment Planning
• SAMHSA, Shared Decision-Making Tools:
Provides resources to help people with OUD
make informed decisions about their care.
www.samhsa. gov/brss-tacs/recovery-
support-tools/shared-decision-making
An accompanying handbook is also available.
https://store.samhsa.gov/product/Decisions-
in-Recovery-Treatment-for-Opioid-Use
-Disorders/SMA16-4993
• SAMHSA, TIP 42, Substance Use Disorder
Treatment for People With Co-Occurring
Disorders: Provides comprehensive
treatment guidance for individuals with
co-occurring mental and substance use
disorders. https://store.samhsa.gov/product/
TIP-42-Substance-Abuse-Treatment-for-
Persons-With-Co-Occurring-Disorders/
SMA13-3992
2-32
Medications for Opioid Use Disorder TIP 63
Part 2 Appendix
Stable Resource Toolkit
Audit-C – Overview
The AUDIT-C is a 3-item alcohol screen that can help identify persons who are hazardous drinkers or have active
alcohol use disorders (including alcohol abuse or dependence). The AUDIT-C is a modifed version of the 10 question
AUDIT instrument.
Clinical Utility
The AUDIT-C is a brief alcohol screen that reliably identifes patients who are hazardous drinkers or have active
alcohol use disorders.
Scoring
The AUDIT-C is scored on a scale of 0-12.
Each AUDIT-C question has 5 answer choices. Points allotted are:
a = 0 points, b = 1 point, c = 2 points, d = 3 points, e = 4 points
• In men, a score of 4 or more is considered positive, optimal for identifying hazardous drinking or active alcohol use
disorders.
• In women, a score of 3 or more is considered positive (same as above).
• However, when the points are all from Question #1 alone (#2 & #3 are zero), it can be assumed that the patient is
drinking below recommended limits and it is suggested that the provider review the patient’s alcohol intake over
the past few months to confrm accuracy.
• Generally, the higher the score, the more likely it is that the patient’s drinking is affecting his or her safety.
Psychometric Properties
For identifying patients with heavy/hazardous drinking and/or Active-DSM alcohol abuse or dependence
MEN1 WOMEN2
≥3 Sens: 0.95 / Spec. 0.60 Sens: 0.66 / Spec. 0.94
≥4 Sens: 0.86 / Spec. 0.72 Sens: 0.48 / Spec. 0.99
For identifying patients with active alcohol abuse or dependence
MEN1 WOMEN2
≥3 Sens: 0.90 / Spec. 0.45 Sens: 0.80 / Spec. 0.87
≥4 Sens: 0.79 / Spec. 0.56 Sens: 0.67 / Spec. 0.94
1. Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT Alcohol Consumption Questions (AUDIT-C): An effective brief screening test
for problem drinking. Arch Internal Med. 1998 (3): 1789-1795.
2. Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorders Identifcation Test (AUDIT):
Validation in a female veterans affairs patient population. Arch Internal Med Vol 165, April 2003: 821-829.
Continued on next page
2-33
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
AUDIT-C Questionnaire
Patient Name: _____________________________________________________ Dates of Visit: ______________________
1. How often do you have a drink containing alcohol?
□ a. Never
□ b. Monthly or less
□ c. 2-4 times a month
□ d. 2-3 times a week
□ e. 4 or more times a week
2. How many standard drinks containing alcohol do you have on a typical day?
□ a. 1 or 2
□ b. 3 or 4
□ c. 5 or 6
□ d. 7 to 9
□ e. 10 or more
3. How often do you have six or more drinks on one occasion?
□ a. Never
□ b. Less than monthly
□ c. Monthly
□ d. Weekly
□ e. Daily or almost daily
AUDIT-C is available for use in the public domain.
Reprinted from material in the public domain.103
2-34
Medications for Opioid Use Disorder TIP 63
Drug Abuse Screening Test (DAST-10)
General Instructions
“Drug use” refers to (1) the use of prescribed or over-the-counter drugs in excess of the directions, and (2) any nonmedical
use of drugs. The various classes of drugs may include cannabis (i.e., marijuana, hashish), solvents (e.g., paint thinner), tran-
quilizers (e.g., Valium), barbiturates, cocaine, stimulants (e.g., speed), hallucinogens (e.g., LSD), or narcotics (e.g., heroin).
The questions do not include alcoholic beverages.
Please answer every question. If you have trouble with a question, then choose the response that is mostly right.
Segment: ____________ Visit Number: ___________ Date of Assessment: ______/______/________
These questions refer to drug use in the past 12 months. Please answer No or Yes.
1. Have you used drugs other than those required for medical reasons? □ No □ Yes
2. Do you use more than one drug at a time? □ No □ Yes
3. Are you always able to stop using drugs when you want to? □ No □ Yes
4. Have you had “blackouts” or “fashbacks” as a result of drug use? □ No □ Yes
5. Do you ever feel bad or guilty about your drug use? □ No □ Yes
6. Does your spouse (or parents) ever complain about your involvement with drugs? □ No □ Yes
7. Have you neglected your family because of your use of drugs? □ No □ Yes
8. Have you engaged in illegal activities to obtain drugs? □ No □ Yes
9. Have you ever experienced withdrawal symptoms (i.e., felt sick) when you stopped □ No □ Yes
taking drugs?
10. Have you had medical problems as a result of your drug use (e.g., memory loss, □ No □ Yes
hepatitis, convulsions, bleeding)?
Comments:
Scoring
Score 1 point for each “Yes,” except for question 3, for which a “No” receives 1 point.
DAST Score: __________
Interpretation of Score:
Score Degree of Problems Related to Drug Abuse Suggested Action
0 No problems reported None at this time
1–2 Low level Monitor, reassess at a later date
3–5 Moderate level Further investigation
6–8 Substantial level Intensive assessment
9–10 Severe level Intensive assessment
Adapted with permission.104,105
2-35
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
DSM-5 Opioid Use Disorder Checklist106
Patient’s Name: ____________________________________________________________ Date of Birth: _______________________
Worksheet for DSM-5 Criteria for Diagnosis of Opioid Use Disorder
DIAGNOSTIC CRITERIA
(Opioid use disorder requires that at least 2 criteria be
met within a 12-month period.)
MEETS
CRITERIA?
Yes OR No NOTES/SUPPORTING INFORMATION
1. Opioids are often taken in larger amounts or over
a longer period of time than intended.
2. There is a persistent desire or unsuccessful efforts
to cut down or control opioid use.
3. A lot of time is spent in activities necessary to
obtain the opioid, use the opioid, or recover from
its effects.
4. Craving, or a strong desire to use opioids.
5. Recurrent opioid use resulting in failure to fulfll
major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or
recurrent social or interpersonal problems caused
or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational
activities are given up or reduced because of
opioid use.
8. Recurrent opioid use in situations in which it is
physically hazardous.
9. Continued use despite knowledge of having a
persistent or recurrent physical or psychological
problem that is likely to have been caused or
exacerbated by opioids.
10. Tolerance,* as defned by either of the following:
(a) a need for markedly increased amounts of
opioids to achieve intoxication or desired effect
(b) markedly diminished effect with continued use
of the same amount of an opioid
11. Withdrawal,* as manifested by either of the
following:
(a) the characteristic opioid withdrawal syndrome
(b) the same (or a closely related) substance is
taken to relieve or avoid withdrawal symptoms
*This criterion is not met for individuals taking opioids solely under appropriate medical supervision.
Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms
Signed: _____________________________________________________ Date: _______________________
2-36
Medications for Opioid Use Disorder TIP 63
TAPS Tool Part I
Directions: The TAPS Tool Part 1 is a 4-item screening for tobacco use, alcohol use, prescription medication
misuse, and illicit substance use in the PAST YEAR. Question 2 should be answered by males, and Question 3
should be answered by females. Each of the four multiple-choice items has fve possible responses to choose
from. Check the box to select your answer.
In the PAST 12 MONTHS:
1. How often have you used any tobacco product (for example, cigarettes, ecigarettes, cigars, pipes, or smokeless
tobacco)?
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
2. How often have you had 5 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass
of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by males.)
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
3. How often have you had 4 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass
of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by females.)
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
4. How often have you used any drugs including marijuana, cocaine or crack, heroin, methamphetamine (crystal meth),
hallucinogens, or ecstasy/MDMA?
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
5. How often have you used any prescription medications just for the feeling, more than prescribed, or that were not
prescribed for you? Prescription medications that may be used this way include opiate pain relievers (for example,
OxyContin, Vicodin, Percocet, or methadone), medications for anxiety or sleeping (for example, Xanax, Ativan, or
Klonopin), or medications for ADHD (for example, Adderall or Ritalin).
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
2-37
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
TAPS Tool Part 2
Directions: The TAPS Tool Part 2 is a brief assessment for tobacco use, alcohol use, illicit substance use, and
prescription medication misuse in the PAST 3 MONTHS ONLY. Each of the following questions and subquestions
has two possible answers, yes or no. Check the box to select your answer.
In the PAST 3 MONTHS:
1. Did you smoke a cigarette containing tobacco? □ Yes □ No
If “Yes,” answer the following questions:
• Did you usually smoke more than 10 cigarettes each day?
• Did you usually smoke within 30 minutes after waking?
□ Yes
□ Yes
□ No
□ No
2. Did you have a drink containing alcohol? □ Yes □ No
If “Yes,” answer the following questions:
• Did you have 4 or more drinks containing alcohol in a day?* □ Yes □ No
(Note: This question should only be answered by females.)
• Did you have 5 or more drinks containing alcohol in a day?* □ Yes □ No
(Note: This question should only be answered by males.)
• Have you tried and failed to control, cut down, or stop drinking?
• Has anyone expressed concern about your drinking?
□ Yes
□ Yes
□ No
□ No
3. Did you use marijuana (hash, weed)? □ Yes □ No
If “Yes,” answer the following questions:
• Have you had a strong desire or urge to use marijuana at least once a week or more often? □ Yes □ No
• Has anyone expressed concern about your use of marijuana? □ Yes □ No
4. Did you use cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No
If “Yes,” answer the following questions:
• Did you use cocaine, crack, or methamphetamine (crystal meth) at least once a week or more often? □ Yes □ No
• Has anyone expressed concern about your use of cocaine, crack, or methamphetamine (crystal
meth)? □ Yes □ No
5. Did you use heroin? □ Yes □ No
If “Yes,” answer the following questions:
• Have you tried and failed to control, cut down, or stop using heroin? □ Yes □ No
• Has anyone expressed concern about your use of heroin? □ Yes □ No
6. Did you use a prescription opiate pain reliever (for example, Percocet or Vicodin) not as □ Yes □ No
prescribed or that was not prescribed for you?
If “Yes,” answer the following questions:
• Have you tried and failed to control, cut down, or stop using an opiate pain reliever? □ Yes □ No
• Has anyone expressed concern about your use of an opiate pain reliever? □ Yes □ No
*One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor.
Continued on next page
2-38
Medications for Opioid Use Disorder TIP 63
TAPS Tool Part 2 (continued)
7. Did you use medication for anxiety or sleep (for example, Xanax, Ativan, or Klonopin)
not as prescribed or that was not prescribed for you?
If “Yes,” answer the following questions:
• Have you had a strong desire or urge to use medications for anxiety or sleep at least once
a week or more often?
• Has anyone expressed concern about your use of medication for anxiety or sleep?
□ Yes
□ Yes
□ Yes
□ No
□ No
□ No
8. Did you use medication for ADHD (for example, Adderall or Ritalin) not as prescribed
or that was not prescribed for you?
If “Yes,” answer the following questions:
• Did you use a medication for ADHD (for example, Adderall or Ritalin) at least once a week or
more often?
• Has anyone expressed concern about your use of medication for ADHD (for example, Adderall
or Ritalin)?
□ Yes
□ Yes
□ Yes
□ No
□ No
□ No
9. Did you use any other illegal or recreational drugs (for example, ecstasy, molly, GHB, □ Yes □ No
poppers, LSD, mushrooms, special K, bath salts, synthetic marijuana ["spice"], or whip-its)?
If “Yes,” answer the following question:
• What were the other drug(s) you used? (write in response)
The complete tool is available online (https://cde.drugabuse.gov/instrument/29b23e2e-e266-f095-e050-bb89ad43472f).
Adapted from material in the public domain.107
2-39
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
Notes
1 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
2 Center for Behavioral Health Statistics and Quality. (2020).
Results from the 2019 National Survey on Drug Use and
Health: Detailed tables. Rockville, MD: Substance Abuse
and Mental Health Services Administration. Retrieved
May 21, 2021, from www.samhsa.gov/data/
3 American Society of Addiction Medicine. (2011).
Defnition of addiction. Retrieved October 30, 2017, from
www.asam.org/resources/defnition-of-addiction
4 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
5 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
6 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
7 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
8 National Cancer Institute. (n.d.). Remission. In NCI
dictionary of cancer terms. Retrieved November 22,
2017, from www.cancer.gov/publications/dictionaries
/cancer-terms?cdrid=45867
9 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
10 McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G.,
Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016).
Performance of the Tobacco, Alcohol, Prescription
Medication, and Other Substance Use (TAPS) Tool for
substance use screening in primary care patients. Annals
of Internal Medicine, 165(10), 690–699.
11 Centers for Disease Control and Prevention. (2020).
Alcohol and public health: Alcohol-Related Disease
Impact (ARDI). Annual average for United States
2011–2015 alcohol-attributable deaths due to
excessive alcohol use. Retrieved April 28, 2021, from
https://nccd.cdc.gov/DPH_ARDI/Default/Report.
aspx?T=AAM&P=1A04A664-0244-42C1-91DE-
316F3AF6B447&R=B885BD06-13DF-45CD-8DD8-
AA6B178C4ECE&M=32B5FFE7-81D2-43C5-A892-
9B9B3C4246C7&F=&D=
12 Warner-Smith, M., Darke, S., Lynskey, M., & Hall, W.
(2001). Heroin overdose: Causes and consequences.
Addiction, 96(8), 1113–1125.
13 Curry, S. J., Krist, A. H., Owens, D. K., Barry, M. J.,
Caughey, A. B., Davidson, K. W., ... & Landefeld, C. S.
(2018). Screening and behavioral counseling interventions
to reduce unhealthy alcohol use in adolescents
and adults: U.S. Preventive Services Task Force
recommendation statement. JAMA, 320(18), 1899–1909.
14 U.S. Preventive Services Task Force. (2018). Final
Recommendation Statement: Unhealthy Alcohol Use
in Adolescents and Adults: Screening and Behavioral
Counseling Interventions. Retrieved January 11, 2020,
from www.uspreventiveservicestaskforce.org/Page/
Document/RecommendationStatementFinal/unhealthy-
alcohol-use-in-adolescents-and-adults-screening-and-
behavioral-counseling-interventions
15 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
16 Babor, T. F., Higgins-Biddle, J. C., Saunders, J. B., &
Monteiro, M. G. (2001). The Alcohol Use Disorders
Identifcation Test: Guidelines for use in primary care (2nd
ed.). Geneva, Switzerland: World Health Organization.
17 Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D., &
Bradley, K. A. (1998). The AUDIT alcohol consumption
questions (AUDIT-C): An effective brief screening test for
problem drinking. Ambulatory Care Quality Improvement
Project (ACQUIP). Alcohol Use Disorders Identifcation
Test. Archives of Internal Medicine, 158(16), 1789–1795.
18 Dawson, D. A., Smith, S. M., Saha, T. D., Rubinsky, A. D.,
& Grant, B. F. (2012). Comparative performance of the
AUDIT-C in screening for DSM-IV and DSM-5 alcohol
use disorders. Drug and Alcohol Dependence, 126(3),
384–388.
19 Substance Abuse and Mental Health Services
Administration, & National Institute on Alcohol Abuse
and Alcoholism. (2015). Medication for the treatment of
alcohol use disorder: A brief guide. HHS Publication No.
(SMA) 15-4907. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
20 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D.,
& Saitz, R. (2009). Primary care validation of a single-
question alcohol screening test. Journal of General
Internal Medicine, 24(7), 783–788.
21 Kalman, D., Morissette, S. B., & George, T. P. (2005).
Co-morbidity of smoking in patients with psychiatric and
substance use disorders. American Journal of Addictions,
14, 106–123.
22 Department of Health and Human Services. (2014). The
health consequences of smoking—50 years of progress: A
report of the Surgeon General. Atlanta, GA: Department
of Health and Human Services, Centers for Disease
Control and Prevention, National Center for Chronic
Disease Prevention and Health Promotion, Offce on
Smoking and Health.
23 Lasser, K., Boyd, J. W., Woolhandler, S., Himmelstein,
D. U., McCormick, D., & Bor, D. H. (2000). Smoking and
mental illness: A population-based prevalence study.
JAMA, 284, 2606–2610.
2-40
Medications for Opioid Use Disorder TIP 63
24 Ong, M. O., Zhou, Q., & Sung, H. (2011). Primary
care providers advising smokers to quit: Comparing
effectiveness between those with and without alcohol,
drug, or mental disorders. Nicotine and Tobacco
Research, 13(12), 1193–1201.
25 U.S. Preventive Services Task Force. (2015). Tobacco
smoking cessation in adults, including pregnant women:
Behavioral and pharmacotherapy interventions.
26 Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., &
Fagerström, K. O. (1991). The Fagerström Test for
Nicotine Dependence: A revision of the Fagerström
Tolerance Questionnaire. British Journal of Addiction,
86(9), 1119–1127.
27 John, U., Meyer, C., Schumann, A., Hapke, U., Rumpf,
H. J., Adam, C., … Lüdemann, J. (2004). A short form
of the Fagerström Test for Nicotine Dependence and
the Heaviness of Smoking Index in two adult population
samples. Addictive Behaviors, 29(6), 1207–1212.
28 U.S. Preventive Services Task Force. (2020). Final
Recommendation Statement—Unhealthy Drug
Use: Screening. Retrieved May 3, 2021, from
https://uspreventiveservicestaskforce.org/uspstf/
recommendation/drug-use-illicit-screening
29 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
30 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
31 McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G.,
Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016).
Performance of the Tobacco, Alcohol, Prescription
Medication, and Other Substance Use (TAPS) Tool for
substance use screening in primary care patients. Annals
of Internal Medicine, 165(10), 690–699.
32 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D.,
& Saitz, R. (2010). A single-question screening test for
drug use in primary care. Archives of Internal Medicine,
170(13), 1155–1160.
33 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M.,
Osterberg, L., & Smith, B. (2015). Screen of drug use:
Diagnostic accuracy of a new brief tool for primary care.
JAMA Internal Medicine, 175(8), 1371–1377.
34 Skinner, H. A. (1982). The Drug Abuse Screening Test.
Addictive Behaviors, 7(4), 363–371.
35 Babor, T. F., Higgins-Biddle, J. C., Saunders, J. B., &
Monteiro, M. G. (2001). The Alcohol Use Disorders
Identifcation Test: Guidelines for use in primary care (2nd
ed.). Geneva, Switzerland: World Health Organization.
36 Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., &
Fagerström, K. O. (1991). The Fagerström Test for
Nicotine Dependence: A revision of the Fagerström
Tolerance Questionnaire. British Journal of Addiction,
86(9), 1119–1127.
37 McNeely, J., Strauss, S. M., Rotrosen, J., Ramautar,
A., & Gourevitch, M. N. (2016). Validation of an audio
computer-assisted self-interview (ACASI) version of the
Alcohol, Smoking and Substance Involvement Screening
Test (ASSIST) in primary care patients. Addiction, 111(2),
233–244.
38 Ali, R., Meena, S., Eastwood, B., Richards, I., & Marsden,
J. (2013). Ultra-rapid screening for substance-use
disorders: The Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST-Lite). Drug and
Alcohol Dependence, 132(1–2), 352–361.
39 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D.,
& Saitz, R. (2010). A single-question screening test for
drug use in primary care. Archives of Internal Medicine,
170(13), 1155–1160.
40 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M.,
Osterberg, L., & Smith, B. (2015). Screen of drug use:
Diagnostic accuracy of a new brief tool for primary care.
JAMA Internal Medicine, 175(8), 1371–1377.
41 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M.,
Osterberg, L., & Smith, B. (2015). Screen of drug use:
Diagnostic accuracy of a new brief tool for primary care.
JAMA Internal Medicine, 175(8), 1371–1377.
42 National Institute on Drug Abuse. (2012). Resource
guide: Screening for drug use in general medical settings.
Rockville, MD: Author.
43 National Institute on Drug Abuse. (2012). Resource
guide: Screening for drug use in general medical settings.
Rockville, MD: Author.
44 Ali, R., Meena, S., Eastwood, B., Richards, I., & Marsden,
J. (2013). Ultra-rapid screening for substance-use
disorders: The Alcohol, Smoking and Substance
Involvement Screening Test (ASSIST-Lite). Drug and
Alcohol Dependence, 132(1–2), 352–361.
45 Schwartz, R. P., McNeely, J., Wu, L. T., Sharma, G., Wahle,
A., Cushing, C., … Subramaniam, G. (2017). Identifying
substance misuse in primary care: TAPS Tool compared to
the WHO ASSIST. Journal of Substance Abuse Treatment,
76, 69–76.
46 Wang, X., Zhang, T., & Ho, W. Z. (2011). Opioids and HIV/
HCV infection. Journal of Neuroimmune Pharmacology,
6(4), 477–489.
47 U.S. Preventive Services Task Force. (2019).
Final Recommendation Statement on Human
Immunodefciency Virus (HIV) Infection:
Screening. Retrieved June 11, 2019, from www.
uspreventiveservicestaskforce.org/Page/Document/
RecommendationStatementFinal/human-
immunodefciency-virus-hiv-infection-screening#consider
48 Centers for Disease Control and Prevention. Testing
Recommendations for Hepatitis C Virus Infection.
Retrieved October 15, 2015, from www.cdc.gov/
hepatitis/hcv/guidelinesc.htm
2-41
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
49 Merrill, J. O., Rhodes, L. A., Deyo, R. A., Marlatt, G. A., &
Bradley, K. A. (2002). Mutual mistrust in the medical care
of drug users: The keys to the “narc” cabinet. Journal of
General Internal Medicine, 17(5), 327–333.
50 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
51 Miller, W. R., & Rollnick, S. (2013). Motivational
interviewing: Helping people change (3rd ed.). New York,
NY: Guilford Press.
52 Center for Substance Abuse Treatment. (1999). Brief
interventions and brief therapies for substance abuse.
Treatment Improvement Protocol (TIP) Series. 34. HHS
Publication No. (SMA) 12-3952. Rockville, MD: Substance
Abuse and Mental Health Services Administration.
53 Miller, W. R., & Rollnick, S. (2013). Motivational
interviewing: Helping people change (3rd ed.). New York,
NY: Guilford Press.
54 Savant, J. D., Barry, D. T., Cutter, C. J., Joy, M. T., Dinh,
A., Schottenfeld, R. S., & Fiellin, D. A. (2013). Prevalence
of mood and substance use disorders among patients
seeking primary care offce-based buprenorphine/
naloxone treatment. Drug and Alcohol Dependence,
127(1–3), 243–247.
55 Hassan, A. N., Howe, A. S., Samokhvalov, A. V., Le Foll,
B., & George, T. P. (2017). Management of mood and
anxiety disorders in patients receiving opioid agonist
therapy: Review and meta-analysis. American Journal on
Addictions, 26(6), 551–563.
56 Hall, W. D., & Strang, J. (2017). Alcohol problems need
more attention in patients receiving long-term opioid
substitution therapy. Lancet Psychiatry, 4(4), 265–266.
57 Saitz, R. (2014). Medical and surgical complications of
addiction. In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz
(Eds.), The ASAM principles of addiction medicine (5th
ed.). Philadelphia, PA: Wolters Kluwer.
58 Soper, R. G. (2014, October 6). Intimate partner violence
and co-occurring substance abuse/addiction. ASAM
Magazine. Retrieved October 16, 2017, from www.asam.
org/magazine/read/article/2014/10/06
/intimate-partner-violence-and-co-occurring-substance
-abuse-addiction
59 Stone, A. L., Becker, L. G., Huber, A. M., & Catalano, R. F.
(2012). Review of risk and protective factors of substance
use and problem use in emerging adulthood. Addictive
Behaviors, 37(7), 747–775.
60 American Society of Addiction Medicine. (2017).
The ASAM appropriate use of drug testing in clinical
addiction medicine. Rockville, MD: ASAM. Retrieved
October 30, 2017, from www.asam.org/resources
/guidelines-and-consensus-documents/drug-testing
61 Lynch, K. (2014). San Francisco General Hospital
laboratory protocol. San Francisco, CA: San Francisco
General Hospital.
62 Warner, E., & Lorch, E. (2014). Laboratory diagnosis.
In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.),
Principles of addiction medicine (5th ed., pp. 332–343).
Philadelphia, PA: Wolters Kluwer.
63 Milone, M. C. (2012). Laboratory testing for prescription
opioids. Journal of Medical Toxicology, 8(4), 408–416.
64 Reisfeld, G. M., Bertholf, R., Barkin, R. L., Webb, F., &
Wilson, G. (2007). Urine drug test interpretation: What do
physicians know? Journal of Opioid Management, 3(2),
80–86.
65 Standridge, J. B., Adams, S. M., & Zotos, A. P. (2010).
Urine drug screening: A valuable offce procedure.
American Family Physician, 81(5), 635–640.
66 Standridge, J. B., Adams, S. M., & Zotos, A. P. (2010).
Urine drug screening: A valuable offce procedure.
American Family Physician, 81(5), 635–640.
67 Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
68 American College of Obstetricians and Gynecologists.
(2017, August). Opioid use and opioid use disorder
in pregnancy.
69 Ali, M. M., Dowd, N., Classen, T., Mutter, R., & Scott,
P. (2017). Prescription drugs monitoring program,
nonmedical use of prescription drug and heroin use:
Evidence from the National Survey of Drug Use and
Health. Addictive Behaviors, 69, 65–77.
70 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
71 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
72 Clinical Tools. (n.d.). DSM 5 opioid use disorder checklist.
Retrieved October 16, 2017, from www.asam.org/docs/
default-source/education-docs/dsm-5-dx-oud-8-28-2017.
pdf?sfvrsn=70540c2_2
73 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
74 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
75 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
2-42
Medications for Opioid Use Disorder TIP 63
76 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 4, CD001333.
77 Krupitsky, E., Zvartau, E., Blokhina, E., Verbitskaya, E.,
Wahlgren, V., Tsoy-Podosenin, M., … Woody, G. E.
(2012). Randomized trial of long-acting sustained-release
naltrexone implant vs oral naltrexone or placebo for
preventing relapse to opioid dependence. Archives of
General Psychiatry, 69(9), 973–981.
78 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
79 McCarty, D., Braude, L., Lyman, D. R., Dougherty, R. H.,
Daniels, A. S., Ghose, S. S., & Delphin-Rittmon, M. E.
(2014). Substance abuse intensive outpatient programs:
Assessing the evidence. Psychiatric Services, 65(6),
718–726.
80 Mee-Lee, D., Shulman, G. D., Fishman, M. J., Gastfriend,
D. R., & Miller, M. M. (Eds.). (2013). The ASAM criteria:
Treatment criteria for addictive, substance-related, and
co-occurring conditions (3rd ed.). Carson City, NV: The
Change Companies.
81 Drug Enforcement Administration. (n.d.). Informational
documents. Retrieved November 21, 2017, from
www.deadiversion.usdoj.gov/pubs/docs/index.html
82 Carroll, K. M., & Weiss, R. D. (2016). The role of
behavioral interventions in buprenorphine maintenance
treatment: A review. American Journal of Psychiatry,
174(8), 738–774.
83 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J.,
Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S.
(2013). A randomized trial of cognitive behavioral therapy
in primary care-based buprenorphine. American Journal
of Medicine, 126(1), 74.e11–74.e77.
84 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J.,
Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S.
(2013). A randomized trial of cognitive behavioral therapy
in primary care-based buprenorphine. American Journal
of Medicine, 126(1), 74.e11–74.e77.
85 Ling, W., Hillhouse, M., Ang, A., Jenkins, J., & Fahey, J.
(2013). Comparison of behavioral treatment conditions
in buprenorphine maintenance. Addiction, 108(10),
1788–1798.
86 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
87 Pettinati, H. M., O’Brien, C. P., & Dundon, W. D. (2013).
Current status of co-occurring mood and substance use
disorders: A new therapeutic target. American Journal of
Psychiatry, 170(1), 23–30.
88 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos,
C., Blazina, I., Zakher, B., … McCarty, D. (2016).
Medication-assisted treatment models of care for
opioid use disorder in primary care settings. Technical
Brief No. 28. Rockville, MD: Agency for Healthcare
Research and Quality.
89 Department of Health and Human Services. (2021,
April 28). Practice guidelines for the administration
of buprenorphine for treating opioid use disorder.
HHS Notice, 86 Fed. Reg. 22439. Retrieved
May 21, 2021, from www.federalregister.gov/
documents/2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-for-treating-
opioid-use-disorder#:~:text=The%20Practice%20
Guidelines%20for%20the%20Administration%20of%20
Buprenorphine,training%2C%20counseling%20and%20
other%20ancillary%20services%20%28i.e%20
90 Department of Health and Human Services. (2021,
April 28). Practice guidelines for the administration
of buprenorphine for treating opioid use disorder.
HHS Notice, 86 Fed. Reg. 22439. Retrieved
May 21, 2021, from www.federalregister.gov/
documents/2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-for-treating-
opioid-use-disorder#:~:text=The%20Practice%20
Guidelines%20for%20the%20Administration%20
of%20Buprenorphine,counseling%20and%20other%20
ancillary%20services%20%28i.e.%2C%20psychosocial%20
services%29
91 Substance Abuse and Mental Health Services
Administration. (n.d.). Apply for a Practitioner Waiver
[Webpage]. Retrieved February 14, 2020, from
www.samhsa.gov/medication-assisted-treatment/
training-materials-resources/apply-for-practitioner-waiver
92 Department of Health and Human Services. (2021,
April 28). Practice guidelines for the administration
of buprenorphine for treating opioid use disorder.
HHS Notice, 86 Fed. Reg. 22439. Retrieved
May 21, 2021, from www.federalregister.gov/
documents/2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-for-treating-
opioid-use-disorder#:~:text=The%20Practice%20
Guidelines%20for%20the%20Administration%20
of%20Buprenorphine,counseling%20and%20other%20
ancillary%20services%20%28i.e.%2C%20psychosocial%20
services%29
93 Bogdanowicz, K. M., Stewart, R., Broadbent, M., Hatch, S.
L., Hotopf, M., Strang, J., & Hayes, R. D. (2015). Double
trouble: Psychiatric comorbidity and opioid addiction—
All-cause and cause-specifc mortality. Drug and Alcohol
Dependence, 148, 85–92.
2-43
TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings
94 Bogdanowicz, K. M., Stewart, R., Chang, C. K., Downs,
J., Khondoker, M., Shetty, H., … Hayes, R. D. (2016).
Identifying mortality risks in patients with opioid use
disorder using brief screening assessment: Secondary
mental health clinical records analysis. Drug and Alcohol
Dependence, 164, 82–88.
95 Department of Health and Human Services. (2016). The
opioid epidemic: By the numbers. Washington, DC:
Department of Health and Human Services.
96 Substance Abuse and Mental Health Services
Administration. (2016). SAMHSA opioid overdose
prevention toolkit. HHS Publication No. (SMA) 16-4742.
Rockville, MD: Author.
97 Centers for Disease Control and Prevention, National
Center for Health Statistics. (2020). Multiple Cause of
Death 2018-2019 on CDC WONDER Online Database,
released in 2020. Retrieved April 29, 2021, from https://
wonder.cdc.gov/mcd.html
98 Scholl, L., Seth, P., Kariisa, M., Wilson, N., & Baldwin,
G. (2019). Drug and opioid-involved overdose deaths—
United States, 2013–2017. Morbidity and Mortality
Weekly Report, 67(5152), 1419.
99 Centers for Disease Control and Prevention, National
Center for Health Statistics. (2020). Multiple Cause of
Death 2018–2019 on CDC WONDER Online Database,
released in 2020. Retrieved April 29, 2021, from https://
wonder.cdc.gov/mcd.html
100Centers for Disease Control and Prevention. (2016).
Increases in drug and opioid-involved overdose deaths—
United States, 2010–2015. Morbidity and Mortality
Weekly Report, 65(50–51), 1445–1452.
101Albert, S., Brason, F. W., II, Sanford, C. K., Dasgupta,
N., Graham, J., & Lovette, B. (2011). Project Lazarus:
Community-based overdose prevention in rural North
Carolina. Pain Medicine, 12(Suppl. 2), S77–S85.
102Walley, A. Y., Xuan, Z., Hackman, H. H., Quinn, E.,
Doe-Simkins, M., Sorensen-Alawad, A., … Ozonoff, A.
(2013). Opioid overdose rates and implementation of
overdose education and nasal naloxone distribution in
Massachusetts: Interrupted time series analysis. British
Medical Journal, 346, f174.
103Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D., &
Bradley, K. A. (1998). The AUDIT alcohol consumption
questions (AUDIT-C): An effective brief screening test for
problem drinking. Ambulatory Care Quality Improvement
Project (ACQUIP). Alcohol Use Disorders Identifcation
Test. Archives of Internal Medicine, 158(16), 1789–1795.
104Skinner, H. A. (1982). The Drug Abuse Screening Test.
Addictive Behavior, 7(4), 363–371.
105Yudko, E., Lozhkina, O., & Fouts, A. (2007). A
comprehensive review of the psychometric properties
of the Drug Abuse Screening Test. Journal of Substance
Abuse Treatment, 32, 189–198.
106American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed., p. 541).
Arlington, VA: American Psychiatric Publishing.
107McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G.,
Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016).
Performance of the Tobacco, Alcohol, Prescription
Medication, and Other Substance Use (TAPS) Tool for
substance use screening in primary care patients. Annals
of Internal Medicine, 165(10), 690–699.
This page intentionally left blank.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Part 3: Medications for Opioid Use Disorder
For Healthcare Professionals
Part 3 of this Treatment Improvement Protocol (TIP) describes general principles of opioid use
disorder (OUD) medication and discusses medication formulations, indications, and dosing
for the three medications used to treat OUD—methadone, naltrexone, and buprenorphine.
TIP Navigation
Executive Summary
For healthcare and addiction professionals,
policymakers, patients, and families
Part 1: Introduction to Medications for Opioid
Use Disorder Treatment
For healthcare and addiction professionals,
policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use
Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment
Counselors, Clients, and Healthcare
Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications for
Opioid Use Disorder
For healthcare and addiction professionals,
policymakers, patients, and families
KEY MESSAGES
• OUD medications are safe and effective
when used appropriately.
• OUD medications can help patients
reduce or stop illicit opioid use and
improve their health and functioning.
• Medication should be considered for
all patients with OUD. Reserve opioid
pharmacotherapies for those with
moderate-to-severe OUD with physical
dependence.
• Patients with OUD should be informed
of the risks and benefts of medication,
treatment without medication, and no
treatment.
• Patients should be advised on where
and how to get treatment with OUD
medication.
• Doses and schedules of medication for
OUD must be individualized.
3-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5
Contents
MEDICATIONS FOR OPIOID USE DISORDER 3-1
Scope of the Problem 3-1
CHAPTER 3A: OVERVIEW OF MEDICATIONS FOR OPIOID USE DISORDER 3-5
Introduction to Medications That Address OUD 3-8
Methadone 3-8
Naltrexone 3-8
Buprenorphine 3-9
Choosing an OUD Medication 3-10
Comparative Efectiveness 3-11
Duration of Medication 3-11
Principles of OUD Medications 3-11
Basic Function 3-11
Intrinsic Activity 3-13
Overview of Medication Indications and Dosing 3-13
CHAPTER 3B: METHADONE 3-17
Formulations 3-17
Pharmacology 3-17
Bioavailability 3-18
Dosing Considerations 3-18
Contraindications 3-18
Precautions and Warnings 3-18
Drug Interactions 3-22
Side Efects 3-25
Assessment 3-25
Patient Selection 3-27
Informed Consent 3-27
Initiating Methadone Treatment 3-29
Day 1 3-29
Dose Titration (Weeks 1 to 2) 3-30
Dose Titration (Weeks 3 to 4) 3-31
Serum Levels 3-31
Dose Stabilization (Week 5 and Beyond) 3-32
Take-Home Medication 3-32
3-iii
TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5
Duration of Methadone Treatment 3-33
Dose Tapering and Methadone Discontinuation 3-34
Methadone Dosing Summary 3-35
Enhancing Access to OUD Medication in OTPs 3-35
Chapter 3B Appendix 3-36
Sample Standard Consent to Opioid Maintenance Treatment Form for OTPs 3-36
CHAPTER 3C: NALTREXONE 3-37
Formulations 3-37
Pharmacology 3-38
Bioavailability 3-38
Dosing Considerations 3-38
XR-NTX 3-38
Patient Selection 3-46
Oral Naltrexone 3-46
Naltrexone Dosing Summary 3-47
XR-NTX 3-47
Oral Naltrexone 3-47
Chapter 3C Appendix 3-48
Sample XR-NTX Treatment Agreement 3-48
Patient Counseling Tool for XR-NTX 3-49
Key Techniques for Reducing Injection Site Reactions 3-50
CHAPTER 3D: BUPRENORPHINE 3-51
Formulations 3-51
History of Approvals 3-51
Implants 3-52
Injectables 3-53
Pharmacology 3-53
Bioavailability 3-53
Metabolism and Excretion 3-54
Dosing Considerations 3-54
Contraindications 3-54
Precautions and Warnings 3-54
Drug Interactions 3-57
Side Efects 3-60
Assessment 3-60
Patient Selection 3-62
Informed Consent 3-62
3-iv
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5
Initiating Buprenorphine Treatment 3-63
Ofce-Based Induction 3-63
Home Induction 3-63
Induction 3-64
Dose Stabilization 3-65
Risk Evaluation and Mitigation Strategy 3-67
Transmucosal Buprenorphine Dosing Summary 3-67
Initiation of Buprenorphine Implants 3-68
Initiation of Buprenorphine Extended-Release Injection 3-69
Duration of Buprenorphine Treatment 3-70
Successful Buprenorphine Treatment 3-70
Dose Tapering and Buprenorphine Discontinuation 3-71
Chapter 3D Appendix 3-73
Buprenorphine Induction and Maintenance Appropriate Use Checklists 3-73
Sample Goal Sheet and Coping Strategies Form 3-75
Sample Goal-Setting Form 3-76
Buprenorphine/Naloxone Home Dosage Schedule: Films or Tablets 3-77
Buprenorphine Treatment Agreement 3-78
Patient Urine Drug Screen and Medication Count Monitoring Form 3-80
Pharmacy Tablet/Film Count Form 3-81
CHAPTER 3E: MEDICAL MANAGEMENT STRATEGIES FOR PATIENTS
TAKING OUD MEDICATIONS IN OFFICE-BASED SETTINGS 3-83
Patient Selection 3-83
Patient Management and Treatment Monitoring 3-84
Course of Treatment 3-85
Role of the Treatment Plan and Treatment Agreement in Medical Management 3-86
Medical Management Strategies 3-86
Administrative Considerations 3-93
Patient Limits 3-93
Diversion Control Policies for OBOT With Buprenorphine 3-94
Storage of Buprenorphine 3-95
Records for Dispensers 3-96
DEA Inspections 3-96
Emergency Protocols and Patient Safety Measures 3-96
Recommendations for Staf Member Training 3-97
Chapter 3E Appendix 3-98
Sample Goal-Setting Form 3-98
Sample Medical Management Visit Form 3-99
Sample Buprenorphine Diversion Control Policy 3-100
3-v
TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5
CHAPTER 3F: MEDICAL MANAGEMENT OF PATIENTS TAKING OUD
MEDICATIONS IN HOSPITAL SETTINGS 3-103
Hospitalized or ED Patients Taking Medication for OUD 3-103
Pain Management 3-103
Buprenorphine 3-104
Methadone 3-105
Naltrexone 3-106
Hospitalized or ED Patients Not Taking Medication for OUD 3-106
Buprenorphine Induction in the Hospital Setting 3-106
Methadone Induction in the Hospital Setting 3-107
Naltrexone Induction in the Hospital Setting 3-108
Medical Management Plan 3-108
Notes 3-109
This page intentionally left blank.
3-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
PART 3 of 5
Medications for Opioid Use Disorder
Part 3 of this TIP describes general principles of OUD medication and discusses medication for-
mulations, indications, and dosing for the three Food and Drug Administration (FDA)-approved
medications used to treat OUD—methadone, naltrexone, and buprenorphine. Part 3 also discusses
patient management and monitoring in outpatient settings other than opioid treatment programs
(OTPs) as well as medical management of patients with OUD in hospital settings.
Scope of the Problem
The United States is experiencing an opioid
addiction epidemic.1 In 2019, an estimated 1.6
million people aged 12 or older had OUD in the
United States.2 Illicit opioid use contributes to
the development of OUD, the spread of HIV and
hepatitis infections, and increasing numbers of
overdose deaths.
OUD is a set of cognitive, behavioral, and
physiological symptoms marked by an inability to
stop opioid use despite negative consequences.3
When severe, it can present as a chronic,
recurring condition with compulsive opioid use
that is often termed “addiction.” It can cause
serious physical and mental health, employment,
legal, and family problems.
Each FDA-approved medication used to treat
OUD can help patients achieve remission and
begin or maintain recovery. Medication
O P I O I D - R E L AT E D
EMERGENCY
DEPARTMENT
visits more than tripled
from 2005 to 2017.4,5
for OUD should be accompanied by individually
tailored medical management and psychosocial
and recovery support services as needed and
wanted by patients to support their remission
and recovery.
Medication supports the efforts of the
individual to achieve lasting recovery.
Exhibit 3.1 defnes key terms in Part 3. For more
defnitions, see the glossary in Part 5 of this TIP.
NOTE TO HEALTHCARE PROFESSIONALS
This TIP cannot replace sound clinical judgment and shared decision making based on
careful patient assessment. Providers should familiarize themselves with FDA labeling
of all OUD medications and current practices standards described here and in other
resources such as the Providers’ Clinical Support System (https://pcssnow.org/resources/
resource-category/clinical-resources/).
3-2
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3.1. Key Terms
Addiction: As defned by the American Society of Addiction Medicine,6 “a primary, chronic disease of
brain reward, motivation, memory, and related circuitry.” It is characterized by inability to consistently
abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems
with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like
other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition,7 does not use the term for diagnostic purposes, but
it commonly describes the more severe forms of OUD.
Induction: Process of initial dosing with medication for OUD treatment until the patient reaches a state
of stability; also called initiation.
Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs
and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as is
the typical standard of care in medical and psychiatric treatment of other chronic illnesses).
Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an
alpha-2 adrenergic agonist if opioid agonist is not available) in tapering doses or other medications to
help a patient discontinue illicit or prescription opioids.
Medical management: Process whereby healthcare professionals provide medication, basic brief
supportive counseling, monitoring of drug use and medication adherence, and referrals, when necessary,
to addiction counseling and other services to address the patient’s medical, mental health, comorbid
addiction, and psychosocial needs.
Offce-based opioid treatment: Providing medication for OUD in outpatient settings other than
certifed OTPs.
Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and
Mental Health Services Administration certifcation and Drug Enforcement Administration registration to
administer and dispense opioid agonist medications that are approved by FDA to treat opioid addiction.
Currently, these include methadone and buprenorphine products. Other pharmacotherapies, such as
naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate
medical, counseling, vocational, educational, and other assessment and treatment services either onsite
or by referral to an outside agency or practitioner through a formal agreement.8
Key Terms Related to OUD Medication Pharmacology
Abuse liability: The likelihood that a medication with central nervous system activity will cause
desirable psychological effects, such as euphoria or mood changes, that promote the medication’s
misuse.
Bioavailability: Proportion of medication administered that reaches the bloodstream.
Cross-tolerance: Potential for people tolerant to one opioid (e.g., heroin) to be tolerant to another
(e.g., methadone).
Dissociation: Rate at which a drug uncouples from the receptor. A drug with a longer dissociation rate
will have a longer duration of action than a drug with a shorter dissociation rate.
Half-life: Rate of removal of a drug from the body. One half-life removes 50 percent from the
plasma. After a drug is stopped, it takes fve half-lives to remove about 95 percent from the plasma. If
a drug is continued at the same dose, its plasma level will continue to rise until it reaches steady-state
concentrations after about fve half-lives.
Continued on next page
3-3
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3.1. Key Terms (continued)
Intrinsic activity: The degree of receptor activation attributable to drug binding. Full agonist, partial
agonist, and antagonist are terms that describe the intrinsic activity of a drug.
Opiates: A subclass of opioids derived from opium (e.g., morphine, codeine, thebaine).
Opioid blockade: Blunting or blocking of the euphoric effects of an opioid through opioid receptor
occupancy by an opioid agonist (e.g., methadone, buprenorphine) or antagonist (e.g., naltrexone).
Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity
at cell receptors in the nervous system that are normally stimulated by opioids. Mu-opioid receptor full
agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced
by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid receptor
partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing
their dose in an opioid-tolerant individual may not produce additional effects once they have reached
their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists.
Methadone and buprenorphine can blunt or block the effects of exogenously administered opioids.
Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the central
nervous system without producing the physiological effects of opioid agonists. Mu-opioid receptor
antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids.
Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They
can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone).
Receptor affnity: Strength of the bond between a medication and its receptor. A medication with
high mu-opioid receptor affnity requires lower concentrations to occupy the same number of mu-opioid
receptors as a drug with lower mu-opioid receptor affnity. Drugs with high mu-opioid receptor affnity
may displace drugs with lower affnity.
This page intentionally left blank.
3-5
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3A: Overview of Medications for
Opioid Use Disorder
Chapter 3A describes general principles of OUD medication and summarizes
formulations, indications, and dosing for the three FDA-approved OUD medications.
There are three FDA-approved medications used
to treat OUD: the mu-opioid receptor partial
agonist buprenorphine, the mu-opioid receptor
full agonist methadone, and the mu-opioid
receptor antagonist naltrexone.
Discussing medications that can treat OUD
with patients who have this disorder is the
clinical standard of care and should cover
at least:
• The proven effectiveness of methadone,
naltrexone, and buprenorphine compared
with placebo and with outpatient counseling
without medication.
• Risks and benefts of treatment with all three
types of medication, treatment without medi-
cation, and no treatment.
• Safety and effectiveness of the medications
when used appropriately.
• Pharmacologic properties, routes of ad-
ministration, and where and how to access
treatment with each medication (Exhibit 3A.1).
3-6
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3A.1. OUD Medications: An Overview9,10
CATEGORY BUPRENORPHINE* METHADONE XR-NTX**
TRANSMUCOSAL DEPOT
Appropriate Typically for Typically for patients Typically for Typically for
patients patients with for whom diversion or patients with patients with
OUD who are safe medication storage OUD who are OUD who have
physiologically are concerns or for physiologically abstained from
dependent on patients who must travel dependent on short-acting
opioids. large distances to the opioids and who opioids for at least
prescriber. meet federal 7–10 days and long-
criteria for OTP acting opioids for at
admission. least 10–14 days.
Pharmacology Opioid receptor
partial agonist
Reduces opioid
withdrawal and
craving; blunts or
blocks euphoric
effects of self-
administered
illicit opioids
through cross-
tolerance and
opioid receptor
occupancy.
Opioid receptor partial
agonist
Reduces opioid
withdrawal and craving;
blunts or blocks
euphoric effects of
self-administered illicit
opioids through cross-
tolerance and opioid
receptor occupancy.
Note: Patients receiving
a depot formulation of
buprenorphine must
be inducted onto
buprenorphine using a
transmucosal product.
Opioid receptor
agonist
Reduces opioid
withdrawal and
craving; blunts or
blocks euphoric
effects of self-
administered
illicit opioids
through cross-
tolerance and
opioid receptor
occupancy.
Opioid receptor
antagonist
Blocks euphoric
effects of self-
administered illicit
opioids through
opioid receptor
occupancy. Causes
no opioid effects.
Reduces opioid
craving.
Patient Tell patients: Tell patients: Tell patients: Tell patients:
education • That they • For implantable rods • That their dose • That they will
will need to (Probuphine®), they will start low need to be opioid
be in opioid will need to be stable and build up free for at least
withdrawal to on no more than slowly to avoid 7–10 days for
receive their frst 8 mg of transmucosal oversedation; short-acting
dose to avoid Suboxone or generic it takes several opioids and at
buprenorphine- equivalents. days for a given least 10–14 days
precipitated
opioid
withdrawal.
• About the risk
of overdose
with concurrent
benzodiazepine
or alcohol use,
with injecting
buprenorphine,
• For subcutaneous
injection (Sublocade®),
they must frst be on
a transmucosal form
of buprenorphine for
at least 7 days at a
dose equivalent to
8 to 24 mg of
buprenorphine.
dose to have its
full effect.
• About overdose
risk in the
frst 2 weeks
of treatment,
especially with
concurrent
benzodiazepine
or alcohol
for long-acting
opioids before
their frst dose of
extended-release
naltrexone (XR-
NTX) to avoid
precipitated
withdrawal (which
may require
hospitalization).
and after use, and after • About the risk of
stopping the stopping the overdose after
medication. medication. stopping the
medication.
Continued on next page
3-7
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3A.1. OUD Medications: An Overview (continued)
CATEGORY BUPRENORPHINE* METHADONE XR-NTX**
TRANSMUCOSAL DEPOT
Administration Daily (or off-label
less-than-daily
dosing regimens)
administration
of sublingual or
buccal tablet or
flm. Subdermal
implants every 6
months, for up to
1 year, for stable
patients. Monthly
subcutaneous
injection of
Subdermal implants
every 6 months, for
up to 1 year, for stable
patients.
Monthly subcutaneous
injection of extended-
release formulation
in abdominal region
for patients treated
with transmucosal
buprenorphine for
at least 1 week.
Daily oral
administration
as liquid
concentrate,
tablet, or oral
solution from
dispersible tablet
or powder (unless
patients can take
some home).
Every 4 weeks or
once-per-month
intramuscular
injection.
extended-release
formulation in
abdominal region
for patients treated
with transmucosal
buprenorphine for
at least 1 week.
Prescribing Physicians, nurse
practitioners (NPs),
and physician
assistants (PAs)
need a waiver to
prescribe. Until
October 1, 2023,
qualifed clinical
nurse specialists,
certifed registered
nurse anesthetists,
and certifed nurse
Prescribers must
have a waiver (as
for transmucosal
buprenorphine) and
complete the product’s
REMS program.
Providers of the
implantable rods must
complete additional
training in their insertion
and removal.
SAMHSA-certifed
OTPs can provide
methadone
for daily onsite
administration
or at-home self-
administration for
stable patients.
Physicians, NPs,
PAs, and, until
October 1, 2023,
clinical nurse
specialists, certifed
registered nurse
anesthetists, and
certifed nurse
midwives can
prescribe or order
administration
by qualifed
midwives also can
obtain a waiver
to prescribe. Any
pharmacy can
fll a prescription
for sublingual
or buccal
formulations. OTPs
can administer/
dispense by OTP
physician order
without a waiver.
Both the implantable rods
and subdermal injections
are available via restricted
distribution programs and
are not available in retail
pharmacies.
OTPs can be providers
of depot formulations of
buprenorphine, provided
the above criteria are
satisfed.
healthcare
professionals.
*Long-acting buprenorphine implants (every 6 months) for patients on a stable dose of buprenorphine are also available
through implanters and prescribers with additional training and certifcation through the Probuphine Risk Evaluation
and Mitigation Strategy (REMS) Program. Extended-release buprenorphine monthly subcutaneous injections are available
only through prescribers and pharmacies registered with the Sublocade REMS Program.
**Naltrexone hydrochloride tablets (50 mg each) are also available for daily oral dosing but have not been shown to be
more effective than treatment without medication or placebo because of poor patient adherence.
3-8
Medications for Opioid Use Disorder TIP 63
Introduction to Medications That
Address OUD
Methadone
Methadone is the most used and most studied
OUD medication in the world.11,12 The World
Health Organization (WHO) considers it an
essential medication.13 Many clinical trials and me-
ta-analyses have shown that it effectively reduces
illicit opioid use, treats OUD, and retains patients
in treatment better than placebo or no medica-
tion.14,15,16 (Part 1 of this Treatment Improvement
Protocol [TIP] further covers methadone’s effcacy.)
In the United States, roughly 1,500 federally
certifed opioid treatment programs (OTPs) offer
methadone for OUD. Increasingly, they also
offer buprenorphine, and some provide XR-NTX.
Core OTP services include medical oversight of
treatment, direct observation of dose administra-
tion, take-home dose dispensing under certain
conditions, counseling, and drug testing.
Some OTPs provide other services, including
mental health and primary care, HIV and hepatitis
C virus care, and recovery support. Even so,
signifcant demand remains for better integration
and coordination of care among OTPs, primary
care services, and mental health services to treat
the range of needs common in people with OUD.17
Coordination is especially important for people
with co-occurring medical, mental, and substance
use disorders, who need multiple services and face
challenges in treatment access and adherence.
Naltrexone
XR-NTX has demonstrated effcacy in
reducing return to illicit opioid use, increasing
treatment retention, and reducing opioid
craving compared with placebo or no medication
Although only OTPs can administer
or dispense methadone for OUD,
all healthcare professionals and
addiction and mental health
counselors should be familiar with
methadone. Their patients may be
enrolled in or need referral to OTPs.
RESOURCE ALERT
Substance Abuse and Mental Health
Services Administration (SAMHSA)
Federal Guidelines for OTPs
Federal Guidelines for Opioid Treatment
Programs offers guidance on how to satisfy
federal OTP regulations (https://store.samhsa.
gov/product/Federal-Guidelines-for-Opioid-
Treatment-Programs/PEP15-FEDGUIDEOTP).
in randomized controlled trials.18,19,20 (See Part
1 for more information on XR-NTX’s effcacy in
OUD treatment.) Because the injectable form was
approved more recently by FDA than methadone
and buprenorphine, XR-NTX has been less
studied than those medications. Physicians, NPs,
and, PAs, and, until October 1, 2023, clinical nurse
specialists, certifed registered nurse anesthetists,
and certifed nurse midwives may prescribe or
order XR-NTX for administration by qualifed staff
members without additional waiver requirements.
XR-NTX initiated prior to release from
controlled environments (e.g., jails, prisons,
residential rehabilitation programs) may be
useful in preventing return to opioid use after
release.21 These settings are typically associated
with extended periods of opioid abstinence, so
maintaining abstinence for suffcient time to start
naltrexone is less challenging than initiating it
among outpatients in the community. Short-term
pilot studies show that offering XR-NTX under
these circumstances can increase treatment
engagement after release.22,23
The oral formulation of naltrexone is not
widely used to treat OUD because of low rates
of patient acceptance and high rates of non-
adherence leading to a lack of effcacy.24 However,
consideration should be given to its use in
situations where adherence can be ensured, such
as with observed daily dosing. Naltrexone is also
FDA approved for the treatment of alcohol use
disorder and therefore may be useful for patients
with both OUD and alcohol use disorder.
3-9
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
RESOURCE ALERT
SAMHSA Brief Guide on the Use
of XR-NTX
SAMHSA’s Clinical Use of Extended-Release
Injectable Naltrexone in the Treatment of
Opioid Use Disorder: A Brief Guide offers
guidance on the use of XR-NTX and is available
online (https://store.samhsa.gov/product
/Clinical-Use-of-Extended-Release-Injectable
-Naltrexone-in-the-Treatment-of-Opioid-Use
-Disorder-A-Brief-Guide/SMA14-4892R).
Buprenorphine
Buprenorphine is effective in retaining patients
in treatment and reducing illicit opioid use, as
demonstrated by many clinical trials comparing
buprenorphine with placebo or no medication.25
Buprenorphine treatment is available throughout
the world. WHO includes it in its list of essential
medicines.26 (See Part 1 for more information on
buprenorphine’s effcacy in OUD treatment.)
Buprenorphine is a partial agonist with a ceiling
effect on opioid activity. Hence, it is less likely
than methadone and other full agonists to cause
respiratory depression in an accidental overdose.
This property contributed to the decision
permitting buprenorphine to be prescribed to
treat opioid dependence outside OTPs.27 That
being said, lethal overdose with buprenorphine is
possible in opioid-naïve individuals or when it is
taken in combination with central nervous system
depressants such as benzodiazepines or alcohol.
Transmucosal buprenorphine is available by pre-
scription through pharmacies, because the Drug
Addiction Treatment Act of 2000 (DATA 2000)
created an exception to the Controlled Substances
Act to permit FDA schedule III, IV, and V med-
ications approved to treat opioid dependence
to be prescribed for that purpose outside OTPs.
Buprenorphine, in various formulations, is the only
medication to which DATA 2000 currently applies.
Qualifying physicians, NPs, and PAs can
prescribe buprenorphine if they receive special
training, obtain a SAMHSA waiver under DATA
2000, and get a unique Drug Enforcement
Administration registration number. Until
October 1, 2023, clinical nurse specialists,
certifed registered nurse anesthetists, and
certifed nurse midwives also are waiver-
eligible to prescribe buprenorphine.
Additionally, providers who are state licensed
and possess a valid Drug Enforcement Agency
registration may be exempted from training
requirements and the required attestation (about
providing patients access to or referrals for psy-
chosocial services) that are normally needed to
obtain the X waiver.28 These providers are limited
to treating no more than 30 patients. This has
greatly increased the number and type of settings
where medication for OUD is available and the
number of patients in treatment. New settings
include non-OTP outpatient addiction treatment
programs, as well as general medical and mental
health practices or clinics (offce-based opioid
treatment). OTPs can also provide buprenorphine.
In 2016, FDA approved buprenorphine implants
(Probuphine) that last about 6 months for patients
stabilized on sublingual or buccal formulations.
Implants have been found to be more effective
than placebo in reducing illicit opioid use among
opioid-dependent patients receiving counseling.29
Implants are available in the same settings as
other buprenorphine formulations but require
waivered providers to receive specifc training
from the manufacturer on insertion and removal
per the FDA-approved REMS (www.accessdata.
fda.gov/scripts/cder/rems/index.cfm?event=
IndvRemsDetails.page&REMS=356).
In 2017, FDA approved a monthly extended-
release buprenorphine injectable formulation
(Sublocade) for patients with moderate-to-
severe OUD who had been initiated and treated
with transmucosal buprenorphine for at least
7 days. The medication is for subcutaneous
abdominal injection by a healthcare provider
DATA 2000 restrictions currently
apply only to buprenorphine used
to treat OUD. They do not apply to
pain treatment using buprenorphine
formulations approved to treat pain.
3-10
Medications for Opioid Use Disorder TIP 63
RESOURCE ALERT
How To Obtain a Waiver To
Prescribe Buprenorphine
• Learn how to qualify for a DATA 2000 physician
waiver: www.samhsa.gov/medication-assisted-
treatment/training-materials-resources/apply-
for-practitioner-waiver
• Learn how to qualify for an NP, PA, clinical
nurse specialist, certifed registered nurse
anesthetist, or certifed nurse midwife waiver:
www.samhsa.gov/medication-assisted-
treatment/training-materials-resources/apply-
for-practitioner-waiver
• Learn how providers may be exempted
from training and psychosocial service
attestation requirements usually needed for
obtaining the X waiver: www.federalregister.
gov/documents/2021/04/28/2021-08961/
practice-guidelines-for-the-administration-
of-buprenorphine-for-treating-opioid-use-
disorder. Also review SAMHSA’s “FAQs About
the New Buprenorphine Practice Guidelines”
at www.samhsa.gov/medication-assisted-
treatment/practitioner-resources/faqs
• Learn how waivered practitioners can
increase their patient limit from 30 to 100,
and then to 275 patients: www.samhsa.gov/
medication-assisted-treatment/training-
materials-resources/apply-for-practitioner-
waiver
Choosing an OUD Medication
Currently, no empirical data indicate which
patients will respond better to which OUD
medications. All patients considering treatment
should be educated about the effectiveness, risks,
and benefts of each of the three OUD medi-
cations, treatment without medication, and no
treatment. Emphasize that OUD medications are
safe and effective when used appropriately, and
point out that these medications can help patients
reduce or stop illicit opioid use and improve their
health and functioning.
Tailor decisions to patients’ medical, psychiatric,
and substance use histories; to their preferences;
and to treatment availability when deciding which
medication and treatment to provide. Consider:
• Patients’ prior response to a medication.
• The medication’s side effect profle.
• The strength of the published data on safety
and effectiveness.
• Patients’ use of other substances (e.g.,
naltrexone is also approved for the treatment
of alcohol dependence).
• Patients’ occupation. For patients in safety-
sensitive occupations, consider XR-NTX.
• Patients’ pregnancy status.*
• Patients’ physical dependence on opioids.
Patients not currently physically dependent on
opioids who are returning to the community
from a residential treatment program or incar-
ceration should have the option of XR-NTX,30
and is intended to be available for ordering and
dispensing (not by prescription to patients) in
healthcare settings that receive special certifca-
tion, pursuant to the FDA-approved REMS (www.
accessdata.fda.gov/scripts/cder/rems/index.
cfm?event=IndvRemsDetails.page&REMS=376).
methadone, or buprenorphine based on which
best suits their needs and circumstances (see
below for special safety dosing considerations
for methadone and buprenorphine in nontoler-
ant patients).31,32,33,34
*Methadone or buprenorphine maintenance is recommended for OUD treatment during pregnancy,35 as these medications
have better maternal and infant outcomes than no treatment or medically supervised withdrawal.36,37,38 Methadone and
buprenorphine are not associated with birth defects and have minimal long-term neurodevelopmental impact on infants.39
However, neonatal abstinence syndrome can occur, which requires hospitalization.40 The American College of Obstetricians and
Gynecologists notes that limited data exist on the safety and effectiveness of naltrexone in pregnancy.41 Starting naltrexone
rather than opioid agonist treatment in pregnancy is not recommended, given the risk of precipitated withdrawal. An expert
panel did not agree on whether women already receiving treatment with naltrexone at the onset of pregnancy should remain
on that medication during pregnancy.42 Patients who were taking naltrexone before their pregnancy should weigh with their
providers the risks regarding unknown potential harm to the developing fetus versus the potential benefts of continuing this
medication during pregnancy.43 Pregnant patients who discontinue naltrexone and return to opioid use should be considered
for methadone or buprenorphine treatment.44
3-11
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
• Patients’ preferences. Respect patients’
preferences for agonist versus antagonist
medication. (See Part 2 of this TIP for an
indepth discussion of treatment planning.)
Comparative Efectiveness
A Cochrane review of 5 randomized clinical
trials with 788 participants found that, when
provided at fexible doses on an outpatient basis,
methadone retained patients in treatment longer
than buprenorphine.45 That same review found
that methadone and buprenorphine equally
reduced illicit opioid use based on 8 studies with
urine drug testing data from 1,027 participants
and 4 studies with self-reported drug use from
501 participants.
There is not yet a Cochrane review on the
comparative effectiveness of XR-NTX and bu-
prenorphine. However, in 2017, two randomized
trials comparing buprenorphine to XR-NTX were
published. A multisite study with 570 partici-
pants in the United States compared initiating
buprenorphine versus XR-NTX at 8 inpatient
treatment programs.46 That study found that
patients randomly assigned to start buprenor-
phine had signifcantly lower return-to-use
rates during 24 weeks of outpatient treatment
compared with those patients assigned to start
XR-NTX. This fnding was because of the known
diffculty in successfully completing induction in
the XR-NTX group. However, comparing only
the subgroups of those participants who did
start their assigned medication, there were no
signifcant between-group differences in return-
to-use rates. In a 12-week trial in Norway with
159 participants who were opioid abstinent at the
time of random assignment, XR-NTX was found
to be noninferior to buprenorphine in terms of
treatment retention and illicit opioid use.47 There
is no extant literature evaluating the comparative
effectiveness of methadone, XR-NTX, buprenor-
phine implant, or extended-release buprenor-
phine injection to one another.
Duration of Medication
Continued treatment with buprenorphine
or methadone is associated with better
outcomes than medically supervised
The TIP expert panel recommends
offering maintenance therapy with
medication, not short-term medically
supervised withdrawal. The TIP expert
panel also supports maintaining
patients on OUD medication for years,
decades, and even a lifetime if patients
are benefting.
withdrawal.48,49,50 Continued treatment with
XR-NTX is associated with better outcomes
than discontinuing XR-NTX.51 Patients should be
informed of the risks and benefts of discontin-
uing medication. Buprenorphine or methadone
can be used for medically supervised withdrawal
over a period of days to weeks (Exhibit 3A.2)
for patients who prefer it to ongoing opioid
agonist treatment. When opioid agonist med-
ications are unavailable, the alpha2-adrenergic
agonist clonidine can relieve some withdrawal
symptoms, although clinical trials found it less
effective.52 Pair medically supervised withdrawal
with the chance to begin XR-NTX. Discontinuing
medication increases risk of return to substance
use and overdose death.53 Stable patients can
continue on their selected OUD medication
indefnitely as long as it is benefcial.54,55,56,57
During medically supervised withdrawal, ancillary
medications can treat some of the withdrawal
symptoms (Exhibit 3A.3).
Principles of OUD Medications
Basic Function
Several factors underlie the development of
addiction involving opioids and the diffculty
people have in achieving and maintaining absti-
nence from them. These factors include:58,59
• Short-term direct and indirect mu-opioid
receptor agonist effects.
• Neuroplastic changes in the brain.
• Genetic, developmental, and environmental
factors (e.g., exposure to high-risk environ-
ments, effect of stress on the hypothalamic–
pituitary–adrenal axis).
3-12
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3A.2. Medically Supervised Withdrawal Using Buprenorphine
or Methadone
Medically supervised withdrawal using buprenorphine or methadone is appropriate when patients:
• Prefer it to treatment without medications, after they have been told the risks and benefts of this
approach compared with treatment with medications.
• Wish to start XR-NTX, which is also FDA approved for the treatment of alcohol dependence.
• Are entering a controlled environment or workplace that disallows opioid agonists.
Data confict on the ideal duration of medically supervised withdrawal.60,61,62Even so, shorter term dose
reductions alone (formerly, “detoxifcation”) are rarely effective.63,64,65
The TIP expert panel does not recommend short-term medically supervised withdrawal alone
because of its high rates of return to illicit opioid use.66,67,68 If patients prefer this approach, it should
be provided with psychosocial treatment.69 XR-NTX treatment should always be considered to
reduce the likelihood of return to use after medically supervised withdrawal is completed and an
adequate period of abstinence achieved,70 as well as to reduce the likelihood of overdose death
upon a return to opioid use.
If withdrawal is appropriate for the patient, the TIP expert panel recommends the following strategies:
• Individualize supervised withdrawal duration per patient preference and response to lower medication
doses.
• Note that patients may beneft from nonopioid medication (e.g., clonidine, ondansetron, loperamide)
or nonsteroidal anti-infammatory medications to manage withdrawal symptoms near the end of the
taper.
• Consider discontinuing dose reduction and increasing the dose if the patient begins to use illicit
opioids.
• Encourage patients to continue receiving counseling, monitoring, and other psychosocial support after
medication discontinuation.
• Urge patients to reenter treatment promptly if they return or think they may return to illicit opioid use.
EXHIBIT 3A.3. Medications for Management of Opioid Withdrawal
Symptoms
SYMPTOM MEDICATION
Nausea Ondansetron, metoclopramide (avoid promethazine; it potentiates opioids)
Diarrhea Loperamide
Anxiety, irritability, sweating Clonidine
Insomnia Diphenhydramine, trazodone
Pain Nonsteroidal anti-infammatory drugs
3-13
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Methadone, buprenorphine, and naltrexone
bind to the mu-opioid receptors in the central
and peripheral nervous systems, gastrointestinal
tract, and vascular system. In the brain, these
receptors mediate opioids’ analgesic and other
effects (e.g., euphoria, respiratory depression,
meiosis).71,72,73 Through modulation of mu-opioid
receptor activity in the brain, these medications
exert therapeutic effcacy in treating OUD.
Intrinsic Activity
Intrinsic activity at the mu-opioid receptor
varies based on whether the medication is a full
agonist, partial agonist, or antagonist (Exhibit
3A.4). The amount of intrinsic activity corre-
sponds to the amount of opioid receptor agonist
effects. A full agonist exerts maximal effects
at increasing doses. A partial agonist has a
ceiling effect. Its opioid effects increase as the
dose increases, but only up to a certain point. An
antagonist binds to the opioid receptor but
does not stimulate the receptor at all. Thus, it
has no intrinsic activity regardless of its dose.
Overview of Medication
Indications and Dosing
Healthcare professionals should consider med-
ication for all patients with OUD. Prescribers
must read FDA labels (i.e., package inserts) for
the medications they prescribe. They must also
evaluate patients clinically to determine the safety
and effectiveness of the medication and dose.
Exhibit 3A.4. Intrinsic Activity of OUD Medications74
100
90
80
70
60
50
40
30
20
10
0
-10 -9 -8 -7 -6 -5 -4
Full Agonist
(Methadone)
Partial Agonist
(Buprenorphine)
Antagonist (Naltrexone)
In
tr
in
si
c
A
ct
iv
it
y
Log Dose of Opioid
3-14
Medications for Opioid Use Disorder TIP 63
Exhibit 3A.5 summarizes OUD medication formu-
lations, indications, and dosing.
• A review of the literature.
• A review of national and international
organizations’ guidelines.
The dosing guidance in subsequent chapters for
methadone (Chapter 3B), naltrexone (Chapter
3C), and buprenorphine (Chapter 3D) is for
healthcare professionals in general medical and
addiction treatment settings. This guidance is
based on:
• FDA-approved medication labels.
• The TIP expert panel’s recommendations.
EXHIBIT 3A.5. OUD Medications: Formulations75,76
GENERIC/
TRADE NAME FORMULATIONS
ACTION AT THE
RECEPTOR FDA INDICATIONS DOSING REGIMEN
Methadone Orally as liquid Mu-opioid receptor Medically supervised Once daily (also
(Methadose, concentrate, full agonist withdrawal and off-label dosing
Dolophine) tablet, or oral
solution of
powder or
dispersible
tablet
maintenance
treatment of opioid
dependence; additional
formulations FDA
approved for pain are
not a focus of this TIP
regimens if
appropriate, such
as split dose twice
daily)
Generic Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also
buprenorphine partial agonist dependence; additional alternative off-label
monoproduct formulations FDA
approved for pain are
not a focus of this TIP
regimens)
Generic
buprenorphine/
naloxone
combination
product
Sublingual
tablet, flm
Mu-opioid receptor
partial agonist
combined with
mu-opioid receptor
antagonist; the latter
is not absorbed
sublingually
Treatment of opioid
dependence
Once daily (also
alternative off-label
regimens)
Buprenorphine/ Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also
naloxone partial agonist dependence alternative off-label
(Zubsolv) combined with
mu-opioid receptor
antagonist; the latter
is not absorbed
sublingually
regimens)
Buprenorphine/ Buccal flm Mu-opioid receptor Treatment of opioid Once daily (also
naloxone partial agonist dependence alternative off-label
(Bunavail) combined with
mu-opioid receptor
antagonist; the latter
is not absorbed
sublingually
regimens)
Continued on next page
3-15
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3A.5. OUD Medications: Formulations (continued)
GENERIC/
TRADE NAME FORMULATIONS
ACTION AT THE
RECEPTOR FDA INDICATIONS DOSING REGIMEN
Buprenorphine/ Sublingual flm; Mu-opioid receptor Treatment of opioid Once daily (also
naloxone may also be partial agonist dependence alternative off-label
(Suboxone) administered
buccally
combined with
mu-opioid receptor
antagonist; the latter
is not absorbed
sublingually
regimens)
Buprenorphine Implants Mu-opioid receptor Maintenance Implants last for
(Probuphine) partial agonist treatment of opioid
dependence in
clinically stable
patients taking 8
mg/day or less of
Suboxone equivalents
6 months and are
then removed,
after which a
second set can be
inserted
Extended-
release
injection
buprenorphine
(Sublocade)
Subcutaneous
injection in
the abdominal
region
Mu-opioid receptor
partial agonist
Treatment of
moderate-to-severe
OUD among patients
initiated and taking
transmucosal
buprenorphine for at
least 7 days
Monthly
Oral naltrexone
(Naltrexone
hydrochloride)
Oral tablet Mu-opioid receptor
antagonist
Block the effects of
administered opioid
agonists
Once daily (also
alternative off-label
regimens)
XR-NTX (Vivitrol) Intramuscular
injection
Mu-opioid receptor
antagonist
Prevent return to
opioid dependence
after medically
supervised opioid
withdrawal
Once monthly by
injection
This page intentionally left blank.
3-17
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3B: Methadone
Chapter 3B provides an overview of methadone pharmacology and discussion of
key methadone dosing considerations for healthcare professionals working in opioid
treatment programs (OTPs).
Methadone is the most studied medication for
opioid use disorder (OUD). Of all OUD pharma-
cotherapies, it is used to treat the most people
throughout the world and has by far the longest
track record (nearly 50 years).77,78 Numerous
clinical trials and meta-analyses have shown that
methadone treatment is associated with signif-
cantly higher rates of treatment retention and
lower rates of illicit opioid use compared with
placebo and with no treatment.79 Other research
associates methadone treatment with reduced
mortality, criminal behavior, and HIV serocon-
version.80,81,82 A Cochrane meta-analysis found
that, at fexible doses, methadone compared
with buprenorphine retains patients in treatment
signifcantly longer and equally reduces illicit
opioid use.83
In the United States, OTPs can offer
methadone to treat OUD, but all providers
who may care for patients with OUD should
be familiar with this treatment.
Formulations
There are several formulations of methadone:
• Liquid concentrate, which is the formulation
most commonly used in treatment programs.
• Powder, which is dissolved in water and
administered as a liquid.
• Dispersible tablets, which are scored tablets
that are dissolved in water.
• Tablets, which are most commonly used
outside of OTPs for analgesia.
Pharmacology
Methadone, a long-acting mu-opioid receptor
full agonist, is a schedule II controlled medica-
tion. It is highly plasma–protein bound and binds
to proteins within tissues throughout the body.84
Through mu-opioid receptor binding and opioid
cross-tolerance to other mu-opioid agonists, at
adequate doses, methadone reduces opioid
craving and withdrawal and blunts or blocks
the effects of illicit opioids.
There is wide individual variability in
methadone pharmacokinetics. The half-life
of methadone can vary from 8 to 59 hours85
depending on the patient. The average is 24
hours.86
Methadone has no ceiling effect. As a full
agonist, increasing doses of methadone produce
maximal physiological effects at the opioid
receptors. Plasma levels reach steady state
in about 5 days (i.e., fve half-lives). Before
achievement of steady state, release from tissue
reservoirs can lead to increasing serum plasma
levels and toxicity, even if the daily methadone
dose is not changed.
Methadone induction, thus, should begin at
a low dose and increase gradually with daily
monitoring over days or weeks. At stable daily
doses, serum levels peak 2 to 4 hours after
dosing, then slowly decrease, providing 24 hours
without overmedication or withdrawal.87
3-18
Medications for Opioid Use Disorder TIP 63
Bioavailability
Methadone is approximately 70 to 80 percent
bioavailable when patients take it orally for
OUD. There is notable individual variability
in bioavailability, ranging from 36 to 100
percent.88,89
The liver’s CYP450 3A4 enzyme is primarily
responsible for metabolizing methadone,90
although CYP2B6 and CYP2D6 enzymes are also
involved.91 At the start of methadone treatment,
methadone can increase CYP3A4 activity
and accelerate its own metabolism in some
individuals.92
Dosing must be individualized because
methadone’s bioavailability, clearance, and
half-life can vary considerably among patients.
Providers should check for potential drug–drug
interactions and monitor patients receiving con-
comitant medications. Some medications (e.g.,
benzodiazepines, anticonvulsants, antibiotics,
antiretroviral agents, some antidepressants)
can induce or inhibit CYP450 enzymes, resulting
in potential changes in methadone serum
concentration, effectiveness, and side effect
profle.
Dosing Considerations
Methadone is indicated for people meeting
OTP admission criteria, which for people 18
and older are:
• Being currently “opioid-addicted”—the term
the Substance Abuse and Mental Health
Services Administration (SAMHSA) OTP
regulations use (e.g., meeting Diagnostic and
Statistical Manual of Mental Disorders, Fifth
Edition,93 criteria for OUD). Not all patients
meeting OUD criteria, particularly those with
mild OUD, are appropriate candidates for
methadone. This is discussed in detail in Part 2
of this Treatment Improvement Protocol (TIP).
• Having a history of at least 1 year of opioid
addiction before admission.
• Providing voluntary, written informed consent.
OTP physicians can waive the history require-
ment per Code of Federal Regulations (42 CFR
8.12)94 for:
• Women who are pregnant.
• Former patients (up to 2 years after
discharge).
• Patients within 6 months of release from
incarceration.
For patients younger than 18, admission
criteria are different. They include two
documented, unsuccessful, medically supervised
withdrawals or treatments without OUD medica-
tion (e.g., methadone) in a 12-month period.
The parent or legal guardian must provide
written informed consent.
Contraindications
Contraindications to treatment with methadone
include an allergy to methadone and other
instances in which opioids are contraindicated,
such as acute asthma, in patients with abnormal-
ly high carbon dioxide blood levels (e.g., from
pulmonary disease or sleep apnea), or paralytic
ileus.
Precautions and Warnings
Respiratory depression
Methadone can cause respiratory depression,
particularly during initial dosing and dose
titration. The goal of methadone dosing in the
frst weeks of treatment (i.e., induction) is to
relieve withdrawal but avoid oversedation and
respiratory depression. Patients who are older
or cachectic or who have chronic obstructive
pulmonary disease are more susceptible to
respiratory depression and should be treated
cautiously with lower doses.
A standard formula for dose induction
for all patients, without careful
monitoring of response to treatment,
and individualized dose adjustment is
inadvisable. This can lead to methadone
intoxication and overdose death.
3-19
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Individualize dosing decisions through daily
monitoring of patients’ responses to treatment.
Opioid tolerance cannot be accurately gauged
based on patient self-reports of the type, amount,
or purity of the opioids they’ve used or of the
severity of their opioid withdrawal symptoms.
The best approach to dosing is to start low
and go slow. Methadone has a relatively long
half-life (24–36 hours or longer). Steady-state
serum levels are generally not reached until
about fve half-lives. This means that patients
will not feel the full effect of the initial dose
for 4 or more days even if the daily dose is the
same. Slow release of methadone from tissues
causes serum levels to continue to increase until
reaching steady state. Initially a dose may seem
appropriate, but the third or fourth day of the
same dose can lead to oversedation and even
respiratory depression and death.95
Use a lower-than-usual starting dose in
individuals with no or low opioid tolerance
(5 mg to 10 mg). Increase doses slowly and with
careful monitoring for patients who:
• Have not used opioids for 5 or more days
(e.g., after leaving a controlled environment).
• Do not use opioids daily.
• Use weaker opioids (e.g., codeine).
Do not determine doses by analgesic
equivalence dose conversion tables for
patients using high doses of prescription opioids,
whether by prescription or illicitly. This can lead
to death owing to incomplete cross-tolerance96
and the unique pharmacology of methadone.
Concurrent substance use disorders (SUDs)
involving benzodiazepines or alcohol
Concurrent misuse of alcohol or benzodiaz-
epines with methadone (or buprenorphine)
increases respiratory depression risk. Use
of alcohol and benzodiazepines (illicit and
prescription) is common in patients with OUD.
Managing OUD with methadone for patients
with alcohol or benzodiazepine use disorders
is challenging and should be undertaken with
care. A 2017 Food and Drug Administration
(FDA) Drug Safety Communication noted that
although concomitant use of buprenorphine or
methadone with benzodiazepines increases the
risk of an adverse reaction, including overdose
death, opioid agonist treatment should not be
denied to patients solely on the basis of their
taking benzodiazepines, because untreated
OUD can pose a greater risk of morbidity and
mortality.97 FDA advises that careful medication
management by healthcare professionals can
reduce risk (see www.fda.gov/downloads
/Drugs/DrugSafety/UCM576377.pdf for more
information).
Strategies to manage patients with concurrent
alcohol or benzodiazepine use disorders
include the following (see also Exhibit 3B.1):
• Obtain permission to communicate with the
benzodiazepine prescriber to confrm the
reason for use, adherence to treatment, and
prescriber awareness of the patient’s OUD. It
can also help to speak (with permission) with
close family members or friends to assess the
extent and impact of any alcohol or benzodi-
azepine misuse.
• Ensure that patients understand the risk
of potential respiratory depression and un-
intentional overdose death when combining
methadone with alcohol, benzodiazepines,
or other central nervous system (CNS)
depressants.
• Determine whether patients require
medically supervised withdrawal or
tapering from alcohol or benzodiazepines.
Patients at risk for serious alcohol or benzo-
diazepine withdrawal syndrome (including
seizures and delirium tremens) may need
inpatient medically supervised withdrawal.
• Attempt gradual outpatient medically
supervised withdrawal for benzodiazepines
when indicated. Some OTPs have the staffng
and capacity to provide a supervised
3-20
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3B.1. Strategies for Managing Benzodiazepine Use by
Patients in OUD Treatment
• Carefully assess the patient’s benzodiazepine
use, including:
- Intent of use.
- Source (check the state’s prescription drug
monitoring program [PDMP]).
- Amount and route of use.
- Binge use.
- Prior overdoses.
- Harms (e.g., car crashes, criminal acts, sleep
trouble).
- Co-use with other substances that further
increase risk for respiratory depression and
overdose.
- Withdrawal history (e.g., seizures, delirium).
• Also assess for:
- Psychiatric and medical comorbidity.
- Motivation for change.
- Psychosocial support system (obtain history
from a signifcant other if the patient permits).
• Gauge level of care and setting needed (e.g.,
residential, outpatient). Inpatient treatment may
be best for patients with poor motivation, limited
psychosocial support, serious or complicated
comorbidity, or injection or binge use.
outpatient taper from benzodiazepines.
This usually requires use of a long-acting
benzodiazepine, management of anxiety and
sleeplessness, and careful monitoring with
observed dosing and toxicology screening. It
may also require lower-than-usual methadone
doses. Engage in outpatient medically super-
vised withdrawal only with patients who are
physically dependent on benzodiazepines
but do not inject or binge. This may only be
successful in a minority of patients. Attempt
the taper while continuing treatment with
methadone, subject to certain conditions that
promote safety and reduce risk.
• Consider increasing counseling frequency
as appropriate.
• Coordinate with other prescribers. Some
patients may have taken appropriately
prescribed benzodiazepines for years with
limited or no evidence of misuse. For such
patients, tapering benzodiazepines may be
contraindicated and unrealistic.
• Address comorbid mental disorders (e.g.,
anxiety, depression) with other medications or
psychosocial treatments, when feasible.
• Provide medically supervised withdrawal from
benzodiazepines or refer to specialty care for
same.
• Create a treatment plan with built-in conditions
(e.g., urine testing, more frequent visits, short
medication supply).
• Frequently review patient progress and
objective outcomes, such as:
- Urine drug testing.
- PDMP reports.
- Psychosocial functioning.
- Reports from signifcant others.
• Revise treatment plans as needed, and
document the rationale for treatment decisions.
Adapted with permission.98
For more information on managing benzodiaze-
pine use, see Management of Benzodiazepines
in Medication-Assisted Treatment (https://ireta.
org/wp-content/uploads/2018/03/BP_Guidelines_
for_Benzodiazepines.pdf).
QTc prolongation and cardiac arrhythmia
Methadone treatment has been associated
with QTc prolongation, which often occurs
without clinical consequences.99,100 Since 2006,
methadone has had an FDA black box warning
on QTc prolongation and Torsades de Pointes.
QTc intervals above 500 milliseconds can
increase risk for this rare ventricular arrhythmia,
which can be lethal.101,102 The prevalence of QTc
prolongation among methadone patients is
3-21
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
QTc prolongation is an abnormally
long time in electrocardiogram (ECG)
tracing between the start of a Q
wave and the end of a T wave. Various
cutoffs defne prolonged QTc interval,
including greater than 450 milliseconds
for men, greater than 460 to 470
milliseconds for women, or greater than
450 milliseconds for either gender.103
However, the faster the heart rate, the
shorter the QTc interval. Hence, correct
the QTc interval for heart rate; divide
the QTc interval in milliseconds by
the square root of the R-R interval in
seconds.104
not known with certainty. It has been estimated
that about 2 percent of patients in methadone
treatment have QTc intervals greater than 500
milliseconds.105 According to methadone’s
FDA label, most Torsades de Pointes cases
occur in patients receiving methadone for pain
treatment, although some cases have occurred
among those in methadone maintenance.106
High methadone doses may be associated with
prolonged QTc intervals.107 Other risk factors
include:108
• Some medications (e.g., antidepressants,
antibiotics, antifungals).
• Congenital prolonged QTc interval.
• Hypokalemia.
• Bradycardia.
There is considerable controversy about how
best to screen for QTc prolongation without
creating barriers to methadone treatment
entry.109 Indeed, a Cochrane review of the liter-
ature was unable to draw any conclusions about
the effectiveness of QTc screening strategies in
preventing cardiac morbidity or mortality among
methadone patients.110 Notwithstanding the
uncertainty about the best approach, OTPs can
take steps to identify patients who may be at
risk for cardiac arrhythmia. The TIP expert panel
concurs with the recommendations of other
expert panels (which included cardiologists)
that OTPs develop a cardiac risk management
plan,111,112 to the extent possible. OTPs should
consider the following elements in crafting a
cardiac risk management plan:
• An intake assessment of risk factors, which
can include:
− Family history of sudden cardiac death,
arrhythmia, myocardial infarction, heart
failure, prolonged QTc interval, or unex-
plained syncope.
− Patient history of arrhythmia, myocardial
infarction, heart failure, prolonged QTc
interval, unexplained syncope, palpitations,
or seizures.
− Current use of medications that may
increase QTc interval (for a complete list,
see https://crediblemeds.org/index.php/
login/dlcheck; register for free for the most
current list).
− Patient history of use of cocaine and
methamphetamines (which can prolong the
QTc interval).
− Electrolyte assessment (for hypokalemia or
hypomagnesemia).
• A risk stratifcation plan, which can include
the following:
− Conduct an ECG for patients with sig-
nifcant risk factors at admission; repeat
within 30 days. Repeat once a year and if
the patient is treated with more than 120
mg of methadone per day.
− Discuss risks and benefts of methadone
with patients with QTc intervals between
450 and 500 milliseconds. Adjust modif-
able risk factors to reduce their risk.
− Do not start methadone treatment for
patients with known QTc intervals above
500 milliseconds. If such an interval is
discovered during treatment, have a risk/
beneft discussion. Strongly consider
lowering the methadone dose, changing
concurrent medications that prolong the
3-22
Medications for Opioid Use Disorder TIP 63
QTc interval, eliminating other risk factors,
and, if necessary, switching to buprenor-
phine. Include follow-up ECG monitoring.
− Consider providing routine universal ECG
screening if feasible, although there is in-
suffcient evidence to formally recommend
doing so.113
Accidental ingestion
Inform patients that accidental ingestion can
be fatal for opioid-naïve individuals, particularly
children. Patients should safeguard take-home
methadone in a lockbox out of the reach of
children.
Neonatal abstinence syndrome (NAS)
Ensure awareness among pregnant patients
or patients who may become pregnant that
NAS can occur in newborns of mothers treated
with methadone. Women receiving methadone
treatment while pregnant should talk with their
healthcare provider about NAS and how to
reduce it. Research has shown that the dose of
opioid agonist medication is not reliably related
to the severity of NAS.114,115,116 Thus, each woman
should receive the dose of medication that best
manages her illness.
Misuse and diversion
Alert patients to the potential for misuse and
diversion of methadone.
Physical dependence
Inform patients that they will develop physical
dependence on methadone and will experience
opioid withdrawal if they stop taking it.
Sedation
Caution patients that methadone may affect
cognition and psychomotor performance and
can have sedating effects. Urge patients to be
cautious in using heavy machinery and driving
until they are sure that their abilities are not
compromised.
Adrenal insufciency
Adrenal insuffciency has been reported in
patients treated with opioids. Ask patients to
alert healthcare providers of nausea, vomiting,
loss of appetite, fatigue, weakness, dizziness,
or low blood pressure.117
Drug Interactions
Methadone has more clinically signifcant
drug–drug interaction than buprenorphine.118
Carefully monitor each patient’s response to
treatment if they are prescribed or stop taking
a CYP450 34A inducer or inhibitor. Methadone
dosages may need to be adjusted up or down
depending on the medication and whether
treatment is starting or stopping. Exhibit 3B.2
lists common interactions between methadone
and other medications.
Medications that induce CYP450 activity can
increase methadone metabolism. Patients
may experience craving or opioid withdrawal
symptoms between doses if they begin these
medications or become sedated if they discon-
tinue them:
• Some antibiotics (e.g., rifampin).
• Antiretrovirals (e.g., efavirenz, nevirapine,
ritonavir).
• Anticonvulsants (carbamazepine, phenobarbi-
tal, phenytoin).
Other medications can inhibit CYP450 activity
and decrease methadone metabolism, causing
symptoms of overmedication (e.g., sedation)
when the medication is started and possibly
withdrawal or cravings when it is stopped.
Among such medications are:119
• Some antibiotics (ciprofoxacin, erythromycin).
• Antacids (cimetidine).
• Antifungals (fuconazole).
• Antidepressants (e.g., fuvoxamine, paroxe-
tine, sertraline).
3-23
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions
Antiretrovirals
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Efavirenz, lopinavir,
nevirapine
Reduction in serum
methadone levels
Induction of
CYP450 enzymes
Clinically signifcant opioid
withdrawal symptoms likely
Abacavir, etravirine,
nelfnavir, ritonavir,
saquinavir, tipranavir
May reduce serum
methadone levels
Induction of
CYP450 enzymes
Clinically pertinent opioid
withdrawal symptoms
unlikely
Didanosine Reduction in didanosine
plasma concentrations
Decreased
bioavailability
Possible decreased effcacy
of didanosine
Zidovudine Increase in zidovudine
plasma concentration
Unknown Risk of zidovudine toxicity
Antidepressants
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Tricyclic: Amitriptyline, Increased risk for Anticholinergic Clinical experience with
clomipramine, desipra- constipation, sedation, effects; blockade combination indicates it is
mine, doxepin, imipra- QTc prolongation, and of human ether-a- generally safe with careful
mine, nortriptyline, pro- arrhythmia go-go-related gene clinical monitoring
triptyline, trimipramine (hERG) channel
Serotonin reuptake May increase serum Inhibition of CYP Clinical experience with
inhibitors: citalopram, es- methadone levels; enzymes; blockade combination indicates it is
citalopram, fuvoxamine, increased risk for of serotonin generally safe with careful
fuoxetine, paroxetine, serotonin syndrome transporter clinical monitoring
sertraline
Monoamine oxidase Increased risk for Inhibition Avoid or use with extreme
inhibitors: Isocarboxazid, serotonin syndrome of serotonin caution and careful clinical
phenelzine, selegiline, metabolism monitoring
tranylcypromine
Serotonin/norepineph- Increased risk for Blockade of Clinical experience with
rine reuptake inhibitors: serotonin syndrome; serotonin combination indicates it is
Duloxetine, desvenlafax- increased risk for QTc transporter; generally safe with careful
ine, venlafaxine prolongation and blockade of clinical monitoring
arrhythmia (venlafaxine) hERG channel
(venlafaxine)
Continued on next page
3-24
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions
(continued)
Antibiotics
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Ciprofoxacin, clarithro-
mycin, erythromycin,
azithromycin
May increase methadone
serum levels; increased
risk for QTc prolongation
and arrhythmia
Inhibition of
CYP enzymes;
blockade of hERG
channel
One case report of sedation
(ciprofoxacin); clinical
monitoring required
Rifampin Reduction in serum
methadone levels
Induction of CYP
enzymes
Severe opioid withdrawal
can occur; need increased
methadone dose
Antifungals
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Ketoconazole, fuconazole May increase methadone
serum levels
Inhibition of CYP
enzymes
Little evidence for important
clinical effects
Anticonvulsants
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Carbamazepine, phenyto-
in, phenobarbital
Reduction in serum
methadone levels
Induction of CYP
enzymes
Severe opioid withdrawal
can occur; will need
increased methadone dose
Antiarrhythmics
CLASS OR SPECIFIC DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Procainamide, quinidine Increases risk for QTc Blockade of hERG Careful clinical monitoring
prolongation and channel required
arrhythmia
Amiodarone May increase methadone
serum levels; increased
risk for QTc prolongation
and arrhythmia
Inhibition of
CYP enzymes;
blockade of hERG
channel
Careful clinical monitoring
required
Continued on next page
3-25
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions
(continued)
Other Drugs and Specifc Classes
CLASS OR SPECIFIC
DRUG INTERACTION
PUTATIVE
MECHANISM NOTES
Benzodiazepines Additive CNS and
respiratory depressant
effects
Increased GABA
activity
Careful clinical monitoring
required
Barbiturates Additive CNS and
respiratory depressant
effects
Increased GABA
activity
Careful clinical monitoring
required
Cimetidine May increase serum
methadone levels
Inhibition of CYP
enzymes
No evidence of major
clinical effect
Naltrexone Precipitated opioid
withdrawal
Displaces
methadone from
mu-opioid receptors
Contraindicated
Adapted with permission.120
Methadone can affect the metabolism of other
medications. For example, zidovudine levels
are reported to increase signifcantly during
methadone treatment. Monitoring for zidovudine
side effects during treatment is warranted.121
Check drug–drug interactions online (www
.drugs.com/drug_interactions.php).
Side Efects
Possible side effects of methadone include
the following (methadone FDA labels list all
potential side effects and are available at
https://dailymed.nlm.nih.gov/dailymed/search
.cfm?labeltype=all&query=METHADONE):
• Constipation
• Nausea
• Sweating
• Sexual dysfunction or decreased libido
• Drowsiness
• Amenorrhea
• Weight gain
• Edema
Assessment
A thorough assessment will help decide whether
a patient is appropriate for admission and meets
federal and any state regulatory requirements
for methadone treatment. (See Part 2 of this TIP
for detailed discussion of screening and assess-
ment.) Before ordering methadone:
• Check the state PDMP for opioid or benzo-
diazepine prescriptions from other providers
(see www.nascsa.org/stateprofles.htm for
links to state PDMPs). Note that methadone
for OUD treatment will not appear in the
PDMP because of confdentiality regulations
regarding substance use treatment records.
Obtain the patient’s consent to release infor-
mation and speak with treating providers to
coordinate care for patient safety.
• Take the patient’s history.
− Conduct a medical, psychiatric, substance
use, and substance use treatment history.
3-26
Medications for Opioid Use Disorder TIP 63
− Assess recent opioid use, including
frequency, quantity, type, route, and
recency (last day of use and use in the
past 30 days).
− Establish OUD diagnosis.
− Assess for other SUDs, including those
that involve alcohol, benzodiazepines,
or stimulants.
• Conduct a physical exam.
− Assess for signs and symptoms of
intoxication. Do not give patients who
are sedated or intoxicated their frst
dose. Instead, assess and treat them
appropriately:
• Identify causes of sedation or
intoxication.
• Ensure the patient’s immediate safety.
• Reassess methadone induction
appropriateness.
• Develop a plan to reattempt induction
or follow a different course of treatment
as appropriate.
• Obtain laboratory tests.
− Conduct drug and alcohol tests. Use
reliable urine tests for drugs, including
opioids (e.g., morphine, methadone,
buprenorphine, oxycodone), benzodiaze-
pines, cocaine, and other drugs that may
be commonly used in the area (e.g., meth-
amphetamine). Obtain an opioid urine or
oral fuid test before initiating treatment.
A negative opioid test in the absence
of clear opioid withdrawal symptoms
indicates that the patient is likely no longer
opioid tolerant; diagnosis should be
reconfrmed. If such patients are to start
taking methadone (rather than naltrexone
for relapse prevention), use caution in
initiating treatment (see the subsection
“First dose for patients without current
opioid tolerance” in the section “Initiating
Methadone Treatment”). Use an alcohol
breathalyzer to estimate the patient’s blood
alcohol content. Do not provide methadone
until the alcohol reading is considerably
below the legal level of alcohol intoxication.
− Assess for signs and symptoms of opioid
withdrawal and physiological depen-
dence. One approach to documenting
withdrawal symptoms is to use a scale such
as the Clinical Opioid Withdrawal Scale
(COWS) or the Clinical Institute Narcotic
Assessment (CINA) Scale for Withdrawal
Symptoms (see “Resource Alert: Opioid
Withdrawal Scales”). Before the frst dose
of methadone, confrm signs of opioid
withdrawal to provide some confdence
that the patient is opioid tolerant and
can begin dose induction. The Naloxone
Challenge should not be routinely used to
determine physiologic withdrawal because
withdrawal symptoms will be visible, if
present, on physical exam if enough time
has passed since last opioid use.122
RESOURCE ALERT
Opioid Withdrawal Scales
The COWS and other opioid withdrawal
scales from Annex 10 of the World Health
Organization’s Guidelines for the Psychosocially
Assisted Pharmacological Treatment of Opioid
Dependence can be downloaded from the
National Center for Biotechnology Information
website (www.ncbi.nlm.nih.gov/books
/NBK143183).
The CINA Scale for Withdrawal Symptoms
also is available online (https://ncpoep.org/wp-
content/uploads/2015/02/Appendix_7_Clinical_
Institute_Narcotic_Assessment_CINA_Scale_
for_Withdrawal_Symptoms.pdf).
3-27
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
− Conduct a pregnancy test. Pregnant
patients with OUD should be treated with
methadone or transmucosal buprenor-
phine.123,124 Discuss risks and benefts of
treatment with methadone and alternative
approaches for each patient and fetus
versus the risks of continued illicit opioid
use. Refer pregnant patients to prenatal
care. Women should be advised that their
menstrual cycle may return to normal once
they are stabilized on medication, and
hence they should use birth control if they
wish to avoid pregnancy.
− Conduct liver function tests. If possible,
assess liver function tests. It is not
necessary to wait for the results of these
tests to begin treatment, because the risk
of not starting methadone outweighs the
benefts of having the test results. Patients
with suspected cirrhosis based on history
and clinical exam should be started at
a lower methadone dose than typical
patients, with more cautious titration.
Patients who have chronic hepatitis can
be treated with methadone. Have a risk/
beneft discussion with patients whose liver
enzymes are at or greater than fve times
the normal level and monitor their liver
function during treatment.
− Conduct hepatitis and HIV testing.
Hepatitis B and C are common among
patients who enter methadone treatment.
HIV infection is also prevalent. Everyone
ages 15 to 65 should be tested at least
once for HIV. Persons at higher risk, such
as people who use drugs by injection,
should be tested annually.125 Anyone who
is injecting or has ever injected drugs, even
once, no matter how long ago, should be
tested for hepatitis C, regardless of their
intention to seek treatment for SUD.126 The
Centers for Disease Control and Prevention
recommends hepatitis B vaccination for
people seeking treatment for SUDs.127
Patient Selection
No evidence clearly predicts which patients
will respond best to methadone treatment
versus alternative pharmacotherapies. Inform
patients of all options and the settings in
which they’re available, as appropriate. (See
“Treatment Planning or Referral” in Part 2 of
this TIP for more on shared decision making.)
Patients who responded well to methadone
in the past should be considered for this
treatment.
Unsuccessful treatment experiences with
methadone in the past do not necessarily
indicate that methadone will be ineffective
again. Motivation and circumstances change
over time. Also, treatment varies by OTP, as it
does for other medical illnesses. Records from
previous providers can contextualize the extent
of past treatment.
Pregnant women should be considered for
methadone treatment.
Methadone (or buprenorphine) treatment
through OTPs may be best for patients who
need a higher level of outpatient structure or
supervision of medication adherence. Tailor
medication decisions to patients’ medical and
substance use histories, patient preferences,
and treatment availability.
Informed Consent
Inform all patients of:
• Their OUD diagnosis and the nature of the
disorder.
• Risks and benefts of methadone and other
OUD medications.
• Risks and benefts of nonmedication
treatments.
Use language and written materials
appropriate to each patient’s
comprehension level to ensure that he
or she understands the options and can
make informed decisions.
3-28
Medications for Opioid Use Disorder TIP 63
•
•
•
•
•
•
•
Inform OTP nursing/medical staff about
prescribed and over-the-counter medications
and herbs (e.g., St. John’s wort) they are
taking, stopping, or changing doses of to allow
assessment of potential drug–drug interactions.
Inform other treating healthcare professionals
that they are receiving methadone treatment.
Plan to avoid driving or operating heavy
machinery until their dose is stabilized.
Learn about other possible side effects of
methadone, including dizziness, nausea,
vomiting, sweating, constipation, edema, and
sexual dysfunction.
Agree to keep take-home doses locked up and
out of the reach of others. Understand that
giving methadone, even small amounts, to
others may be fatal.
Inform providers if they become pregnant.
Understand that stopping methadone increases
their risk of overdose death if they return to illicit
opioid use.
EXHIBIT 3B.3. Key Points of Patient Education for Methadone
Before starting OUD treatment with methadone,
patients should:
•
•
•
•
•
Be told that the methadone dose is started low
and increased slowly over days and weeks with
monitoring, because it takes 4 or more days
for the body to adjust to a dose change. This is
necessary to avoid the risk of overdose.
Understand that the goal of the frst weeks of
treatment is to improve withdrawal symptoms
without oversedation. Patients should inform
providers if they feel sedated or “high” within the
frst 4 hours after their dose.
Learn the symptoms of methadone intoxication
and how to seek emergency care. The frst 2
weeks of treatment have the highest risk of
overdose.
Be aware that rescue naloxone does not last
very long, so they should remain in emergency
care for observation if they are treated for opioid
overdose.
Know that concurrent alcohol, benzodiazepine,
or other sedative use with methadone increases
the risk of overdose and death.
Patients should sign consent forms before
starting treatment. The Chapter 3B Appendix
provides a sample consent form for treatment in
an OTP.
Educate patients about what to expect when
receiving methadone treatment (Exhibit 3B.3).
Caution them against using alcohol and drugs
during methadone treatment. Warn them of
the increased risk of overdose during the frst 2
weeks of treatment. Also warn them that discon-
tinuing treatment and returning to opioid use
will increase their risk of overdose. Document
patient education in the medical record.
Educate patients about the importance of
safe storage of take-home methadone doses.
Discuss with patients where they will store their
take-home medication. Advise them against
storing medication in common areas of the home
RESOURCE ALERT
Patient and Family Member
Educational Resources
Decisions in Recovery: Treatment for Opioid
Use Disorder offers information for patients on
the use of medications for OUD (https://store
.samhsa.gov/product/SMA16-4993).
Medication-Assisted Treatment for Opioid
Addiction: Facts for Families and Friends
offers information for family members and
friends (https://portal.ct.gov/-/media/DMHAS/
Opioid-Resources/MATInfoFamilyFriendspdf.
pdf).
3-29
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
where visitors or children would have access,
such as kitchens and bathrooms. Take-home
doses should be kept in their original childproof
packaging in a lockbox. The key should not be
left in the box. Inform patients that any portion
of a dose taken by another person, a child,
or pet can be deadly. If this occurs, call 9-1-1
immediately.
Initiating Methadone Treatment
Observing patients directly when they take
doses early in treatment is not just required;
it’s benefcial. It maximizes adherence, provides
a daily opportunity to assess response to the
medication, and minimizes the likelihood of med-
ication diversion. Federal OTP regulations permit
patients to receive one take-home dose per
week, given routine clinic closure on weekends.
Patients who demonstrate progress can earn
one additional take-home dose per week for the
frst 90 days of treatment at the OTP medical
director’s discretion. All other doses are directly
observed at the clinic in the frst 90 days.
The goal of initiating methadone treatment is to
increase the patient’s methadone dose gradually
and safely, stabilizing the patient and reducing
his or her opioid use while recognizing that the
risk of dropout or overdose from illicit opioid use
may increase if induction is too slow.
Day 1
The frst dose should reduce opioid withdrawal
symptoms. Perform induction cautiously; it’s
impossible to judge a patient’s level of tolerance
with certainty. For patients addicted to prescrip-
tion opioids, opioid conversion tables should not
be relied on to determine methadone dosage.
First dose for patients with opioid tolerance
The frst dose for patients tolerant to opioids
is generally between 10 mg and 30 mg
(30 mg is the maximum frst dose per federal
OTP regulations). After the frst dose, patients
should remain for observation for 2 to 4 hours if
possible to see whether the dose is sedating or
relieves withdrawal signs.
• If withdrawal symptoms lessen, the patient
should return the next day to be reassessed
and to continue the dose induction process.
• If sedation or intoxication occurs after the frst
dose, the patient should stay under observa-
tion at the clinic until symptoms resolve. In
this case, the patient should be reassessed the
following day, and the subsequent day’s dose
should be substantially reduced. Extremely
rarely, the patient will need to be treated for
overdose with naloxone. If necessary, begin
rescue breathing and call 9-1-1.
• If the patient shows neither sedation nor
reduction of objective signs of opioid with-
drawal during the 2- to 4-hour waiting period,
administer another 5 mg dose. A fnal 5 mg
dose after another waiting period of 2 to 4
hours can be administered if necessary. The
maximum total methadone dose on the frst
day of treatment should not exceed 40 mg.128
However, caution dictates against exceeding
a total frst day’s dose of 30 mg except in rare
cases. In such cases, the patient should be
carefully monitored on subsequent days to
rule out oversedation.
• Patients transferring from another OTP
whose methadone dose and last date of
medication administration can be confrmed
by the medical staff and documented in the
medical record can be continued on the same
methadone dose administered in the original
OTP, even if the dose exceeds the maximum
permitted 40 mg.
For some patients, the lower range of initial
doses is best. Dose with 10 mg to 20 mg in
patients who:
• Are ages 60 and older.
• May have lower levels of opioid tolerance
based on their recent history.
• Use sedating medications, such as benzodiaz-
epines, antipsychotics, or antidepressants.
• Engage in problem drinking or have alcohol
use disorder.
• Take medications that can increase
methadone serum levels or are stopping
medications that decrease methadone serum
levels.129
3-30
Medications for Opioid Use Disorder TIP 63
• Have medical disorders that may cause
hypoxia, hypercapnia, or cardiac arrhythmias.
These include:
− Asthma, chronic obstructive pulmonary
disease, and kyphoscoliosis.
− Obesity.
− Sleep apnea.
− QTc prolongation.
− A family history of cardiac arrhythmias,
fainting or dizziness, or sudden death.
− Cor pulmonale.
− Electrolyte abnormalities, such as hypoka-
lemia or hypomagnesemia.
First dose for patients without current
opioid dependence
In some circumstances, patients who are
not currently dependent on opioids may
be admitted to an OTP (e.g., individuals
with a history of OUD who are returning from
controlled environments).130 In these instances,
consider treatment with extended-release
naltrexone (XR-NTX) to avoid establishing new
physiological opioid dependence. Instead of
starting methadone, consider starting with a low
dose of buprenorphine because of buprenor-
phine’s superior safety threshold.131 In one such
study, 1 mg of buprenorphine was the starting
dose, which was increased slowly132 (see Chapter
3D of this TIP). If XR-NTX and buprenorphine are
not available, or the patient prefers methadone
treatment, consider starting methadone at a 5
mg daily dose (as was done in one study133) after
discussing risks and benefts with the patient.
Titrate the dose much more slowly than for
patients who are opioid tolerant. Increase
initially by 5 mg about every week, based on
patient response. Doses can be increased
somewhat more rapidly after careful assessment
of response if the patient begins to use illicit
opioids. As with other methadone dosing,
induction in these cases should not be based
on a standing order.
Dose Titration (Weeks 1 to 2)
The goals of early dose titration for patients
with current opioid dependence starting on
Day 2 of the frst week of treatment through
stabilization are to avoid sedation at peak
serum levels and to gradually extend time
without opioid withdrawal symptoms and
craving. When patients attend the program,
before dose administration, nursing and/or
medical staff members should ask patients
whether they felt sedation, opioid intoxication
effects, or opioid withdrawal symptoms 2 to
4 hours after their methadone administration
the prior day (Exhibit 3B.4). Doses should be
decreased for reports of symptoms of opioid
intoxication or oversedation. Dosing must be
individualized based on careful patient assess-
ment and generally should not be increased
every day, because plasma methadone levels
do not reach steady state until about fve
methadone half-lives (Exhibit 3B.5).
Even when holding the methadone dose
constant over several days, the patient’s
methadone serum level will rise each day until it
reaches steady state (Exhibit 3B.5). For example,
if the patient remains on 20 mg per day for the
frst few days of induction, the serum level on
Day 2 would refect the 20 mg second day’s dose
plus 10 mg that remained in the body from the
frst day’s dose (for the equivalent single dose
total of 30 mg). The third day would refect the
20 mg third day’s dose, plus 10 mg remaining
in the body from the second day’s dose, and 5
mg remaining from the frst day’s dose (for the
equivalent single dose total of 35 mg), and so
on. Patients who report relief from withdrawal
4 to 12 hours after their last dose may beneft
from staying at that same dose for a few days
so that their serum level can stabilize.134
An American Society of Addiction Medicine
expert panel recommended increasing the
methadone dose in this phase by 5 mg or less
every 5 or more days.135 Other expert recom-
mendations suggest somewhat faster dose
increases,136 including increases of 5 mg to 10
mg no sooner than every 3 to 4 days.137,138
3-31
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Se
ru
m
M
et
h
ad
on
e
Le
ve
l
1 2 3 4 5 6 7 8 9 10
Time (Days)
EXHIBIT 3B.4. Using Signs and Symptoms To Determine Optimal
Methadone Level
Methadone
Comfort
Zone
Serum
Level
0 2 4 6 8 10 12 14 16 18 20 22 24
Opioid Overmedication Signs:
Pinpoint pupils, drowsy or nodding off, listless mental status, itching/scratching,
fushing, decreased body temperature, slowed heartbeat and/or respirations
Opioid Withdrawal—Subjective Symptoms:
Drug craving, anxious feelings or depression, irritability, fatigue, insomnia, hot/cold
fashes, aching muscles/joints, nausea, disorientation, restlessness
Severe Opioid Withdrawal—Objective Signs:
Dilated pupils, illicit opioid use, “goose fesh,” perspiring, shaking, diarrhea, vomiting, runny
nose, sneezing, yawning, fever, hypertension, increased heartbeat and/or respirations
Peak
Trough
No Illicit Opioid Use
No Withdrawal or Overmedication
Hours
Adapted with permission.139
EXHIBIT 3B.5. Steady-State
Methadone Concentration
Reached in About 5 Days
Adapted with permission.140,141
The most important principle is to individualize
dose induction based on careful assessment of
the patient’s response to the medication.
Dose Titration (Weeks 3 to 4)
Methadone doses can be increased further
in 5 mg increments about every 3 to 5 days
based on the patient’s symptoms of opioid
withdrawal or sedation.142 Patients who miss
more than four doses must be reassessed. Their
next methadone dose should be decreased
substantially and built back up gradually. It
may be necessary to restart the dose induction
process from Day 1. Be aware of any specifc
state requirements regarding missed doses.
Serum Levels
Dosing must be individualized because meth-
adone’s bioavailability, clearance, and half-life
vary among patients, affecting their clinical
3-32
Medications for Opioid Use Disorder TIP 63
responses and requiring doses to be changed.
Many factors can affect serum levels and clinical
responses to treatment. Along with age and diet,
these factors include:
• Other medications and herbs (e.g., St. John’s
wort).
• Genetic differences in metabolizing enzymes.
• Pregnancy.
• Changes in urinary pH.143
Consider measuring serum methadone levels
in patients who, after being on a stable
methadone dose, report feeling drowsy 2 to
4 hours after dose administration but develop
craving or withdrawal symptoms before the
next dose is due to be administered. This
may occur in the third trimester of pregnancy,
when concomitant medications interact with
methadone, or when patients rapidly metabolize
opioids. In such cases, consider dividing the daily
methadone dose into twice-daily dosing.144
To assess serum methadone levels, draw peak
and trough blood specimens at about 3 hours
and 24 hours, respectively, after dose administra-
tion. Serum methadone levels generally correlate
with methadone dose,145 but there is no defned
therapeutic window based on serum methadone
level because response varies widely among
patients. Minimum trough methadone levels of
300 ng/mL to 400 ng/mL may be associated with
reduced likelihood of heroin use,146 but deter-
mining the therapeutic dose should depend
on the overall patient response, not the serum
plasma levels. Peak:trough ratios above 2:1 may
indicate rapid metabolism.147
Dose Stabilization (Week 5 and Beyond)
Once the patient achieves an adequate dose,
extended continuation is possible without
dose adjustment. Continuing treatment goals
are to avoid sedation, eliminate withdrawal and
craving, and blunt or block euphoric effects of
illicit opioids.
The TIP expert panel advises against
arbitrary methadone dosage caps.
There may be reasons to further adjust the
dose, including:
• Changes in health that can affect medica-
tions (e.g., acute hepatitis, exacerbation of
pulmonary disease, sleep apnea).
• Changes in patient medications.
• Pregnancy. Increased metabolism in the
last trimester may warrant dose increase or
split dosing.148,149 This may require a
SAMHSA exception for daily take-home
half-doses via an SMA-168 Exception Request
(www.samhsa.gov/medication-assisted
-treatment/opioid-treatment-programs
/submit-exception-request).
• Concurrent illicit opioid or other drug or
alcohol use.
As illicit opioid use stops and stabilization is
achieved, the patient may wish to lower the
dose to reduce any unpleasant side effects.
Typical stabilization doses of at least 60 mg are
associated with greater treatment retention;
80 mg to 120 mg150 is the typical daily range.151
However, there is wide variation, and some
patients beneft from higher daily doses.
Take-Home Medication
OTPs can provide gradually increasing
numbers of take-home doses to patients who
discontinue illicit drug use and begin achieving
treatment goals, commensurate with their
tenure in the program. This provides a powerful
incentive for patients to achieve treatment
goals.152 It also furthers patients’ recovery goals
by allowing them to attend work, school, or
other activities without daily OTP visits.
Federal OTP regulations describe the
conditions under which take-home doses
are permitted. Some states have additional
regulations. OTPs should be familiar with these
regulations and have written procedures to
address take-home dosing.
3-33
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
The benefts of take-home doses must
outweigh the risks and further patients’
rehabilitation goals. When deciding whether
patients can handle the responsibility of
take-home doses of methadone or buprenor-
phine, OTP medical directors should consider
whether patients demonstrate:
• No recent misuse of substances.
• Regular clinic attendance.
• No serious behavioral problems at the clinic.
• No recent criminal activity (e.g., selling drugs).
• Stability at home and in social relationships.
• Suffcient time in treatment.
• Ability and intent to store take-home
medication safely.
• Rehabilitative benefts from decreasing the
frequency of clinic attendance that outweigh
the potential risks of diversion.
Federal regulations based on patients’ time
in treatment determine eligibility to be
considered for receiving take-home doses of
methadone (but buprenorphine is not bound
by these limits):
• One earned dose/week (beyond a weekly
clinic closure day or federal holiday, when
clinics typically close) in the frst 90 days of
treatment
• Two doses during the second 90 days
• Three doses during the third 90 days
• Up to 6 doses during the last 90 days
• Up to 2 weeks of doses after 1 year
• Up to 1 month of doses after 2 years
Assessing responsible handling of
take-home doses
Methadone diversion is a risk. People with
OUD who are not in treatment more frequently
use illicit methadone to self-medicate withdrawal
symptoms than to achieve euphoria.153,154 Still,
diversion is a public health risk; people who
self-medicate may not know what dose they are
taking. Moreover, opioid-naïve people (including
children) who ingest methadone can die of
methadone intoxication.
OTPs must assess patients’ adherence to
responsible take-home-dose handling and
have a diversion control plan. The plan may
require that the OTP:
• Remain open 7 days per week or arrange
dosing at another clinic on days the clinic is
closed for certain patients to avoid providing
take-home doses to new or unstable patients.
• Contact patients randomly and request
that they return their take-home containers
within a day or two to see whether they still
have the medication in their possession or
have altered the medication in any way.
• Establish an appropriate drug testing
program with policies to prevent falsifcation
of specimens and to respond to tests that are
negative for methadone.
• Require patients to store their take-home
medication in a lockbox to prevent theft or
accidental use by children or others.
Duration of Methadone
Treatment
Longer lengths of stay in methadone treatment
are associated with superior treatment
outcomes.155 Leaving methadone treatment
is associated with increased risk of death from
overdose and other causes.156,157 Patients should
continue as long as they beneft, want to, and
develop no contraindications.
RESOURCE ALERT
Guidance on Federal Take-Home
Methadone Dose Regulations
For more information on federal take-home
dose regulations for OTPs, see SAMHSA’s
Federal Guidelines for Opioid Treatment
Programs (https://store.samhsa.gov/product/
Federal-Guidelines-for-Opioid-Treatment-
Programs/PEP15-FEDGUIDEOTP).
3-34
Medications for Opioid Use Disorder TIP 63
•
•
•
•
•
The TIP expert panel considers
arbitrary time limits on OUD treatment
with methadone to be medically
unwarranted and inappropriate. They
pose a risk to patients and the public.
Dose Tapering and Methadone
Discontinuation
Discuss risks and benefts with patients who
wish to discontinue treatment. Explore their
reasons for wanting to discontinue and solutions
for potential barriers to treatment, which may
include:
Logistics (e.g., travel, scheduling).
Transportation services, including publicly
funded ride services, ride sharing, or peer
support workers, may be available. If not,
transferring patients to a closer OTP or to
one with more suitable hours of operation
may resolve the problem.
Costs. Providers can help patients explore
publicly supported treatment options or apply
for insurance.
Side effects. Changing the dose or treating
side effects may resolve the problem.
Opinions of friends or family. When external
pressure from family or friends drives the
decision, a discussion with the patient and
those individuals may help.
A desire to switch to buprenorphine or
XR-NTX treatment. These options should be
discussed.
Caution patients who are not yet stable
against discontinuing treatment, because of
high rates of return to illicit opioid use and
increased chance of overdose death.158 Discuss
the alternative of switching to a different OUD
medication. Give patients who stop treatment
information about overdose prevention and
encourage them to return to treatment. Prescribe
naloxone to use in case of overdose.
Create a plan collaboratively with stable
patients who wish to discontinue treatment
that addresses:
• Gradually tapering their dose.
• Increasing psychosocial and recovery
supports.
• Discontinuing dose reduction if necessary.
• Returning to medication treatment after
discontinuation if they return to illicit opioid
use.
• Increasing dosage if destabilization occurs.
Individualize the pace of methadone dose
reduction to the patient’s response. One
approach is to decrease the methadone dose
gradually by 5 to 10 percent every 1 to 2 weeks.
Once patients reach a relatively low dose, often
between 20 mg and 40 mg, they may begin to
feel more craving. Some patients may choose
to switch to buprenorphine for a period to
complete the dose reduction. They may also
wish to begin XR-NTX after an appropriate
period of opioid abstinence.
Encourage patients to use techniques for
preventing return to use, such as participating
in recovery support groups and gaining support
from counseling and family. Doing so can help
patients succeed in tapering off their medication.
RESOURCE ALERT
Guidance on Opioid Overdose
Prevention
For more information on preventing opioid
overdose, see the SAMHSA Opioid Overdose
Prevention Toolkit (https://store.samhsa.gov/
product/Opioid-Overdose-Prevention-Toolkit/
SMA18-4742).
3-35
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Methadone Dosing Summary
The initial goal is to reduce opioid withdrawal
and craving safely.
• Use the “start low and go slow” approach but
increase dose at a rate that minimizes chances
of continued illicit drug use, while monitoring
for side effects.
• Increase doses gradually over several weeks.
• Assess for sedation at peak serum concentra-
tion (2–4 hours after the dose).
The eventual target is an adequate dose that:
• Stops withdrawal symptoms for 24 hours.
• Reduces or eliminates craving.
• Blunts or blocks euphoria from self-
administered illicit opioids.
In general, after induction is complete, higher
doses are more effective than lower doses.
Enhancing Access to OUD
Medication in OTPs
Individuals on waiting lists for OTPs should
receive interim methadone maintenance
treatment. People on waiting lists typically
continue to use illicit opioids. Many never gain
admission through the waiting list process.
Federal OTP regulations permit use of interim
methadone maintenance to address this problem
by providing methadone treatment for up to 120
days to someone on an OTP waiting list. Routine
counseling and treatment planning are not
required during this period.
Interim methadone maintenance has
been shown to be more effective than a
waiting list to facilitate entry into com-
prehensive methadone treatment and to
reduce illicit opioid use, according to two
randomized trials.159,160 Interim methadone
requires approval by SAMHSA and the
state opioid treatment authority. For more
detailed information on interim methadone
maintenance, see SAMHSA’s Federal
Guidelines for Opioid Treatment Programs
(https://store.samhsa.gov/product/Federal-
Guidelines-for-Opioid-Treatment-Programs/
PEP15-FEDGUIDEOTP).
OTPs can overcome geographic barriers
by opening a medication unit of the parent
OTP site. Under the aegis of a certifed OTP,
a medication unit may provide methadone
or buprenorphine administration, dispensing
capacity, and urine drug testing, but not coun-
seling. The parent clinic must provide counseling
and other required services. Such arrangements
can lessen the amount of time required to drive
to a parent OTP location in large states with rural
populations.
SAMHSA’s Federal Guidelines for Opioid
Treatment Programs offers more information
on medication units and other OTP regulations
(https://store.samhsa.gov/product/Federal-
Guidelines-for-Opioid-Treatment-Programs/
PEP15-FEDGUIDEOTP).
3-36
Medications for Opioid Use Disorder TIP 63
Chapter 3B Appendix
Sample Standard Consent to Opioid Maintenance Treatment Form for OTPs
CONSENT TO PARTICIPATE IN METHADONE OR BUPRENORPHINE TREATMENT
Patient’s Name: _____________________________________________________ Date: _______________
I authorize and give voluntary consent to _________________________________ [insert name of program]
to dispense and administer medications—including methadone or buprenorphine—to treat my opioid
use disorder. Treatment procedures have been explained to me, and I understand that I should take my
medication at the schedule determined by the program physician, or his/her designee, in accordance
with federal and state regulations.
I understand that, like all other medications, methadone or buprenorphine can be harmful if not taken
as prescribed. It has been explained to me that I must safeguard these medications and not share them
with anyone because they can be fatal to children and adults if taken without medical supervision.
I also understand that methadone and buprenorphine produce physical opioid dependence.
Like all medications, they may have side effects. Possible side effects, as well as alternative treatments
and their risks and benefts, have been explained to me.
I understand that it is important for me to inform any medical and psychiatric provider who may treat
me that I am enrolled in an opioid treatment program. In this way, the provider will be aware of all the
medications I am taking, can provide the best possible care, and can avoid prescribing medications that
might affect my treatment with methadone or buprenorphine or my recovery.
I understand that I may withdraw voluntarily from this treatment program and discontinue the use of
these medications at any time. If I choose this option, I understand I will be offered medically supervised
withdrawal.
For women of childbearing age: Pregnant women treated with methadone or sublingual or buccal
buprenorphine have better outcomes than pregnant women not in treatment who continue to use opioid
drugs. Newborns of mothers who are receiving methadone or buprenorphine treatment may have opioid
withdrawal symptoms (i.e., neonatal abstinence syndrome). The delivery hospital may require babies
who are exposed to opioids before birth to spend a number of days in the hospital for monitoring of
withdrawal symptoms. Some babies may also need medication to stop withdrawal. If I am or become
pregnant, I understand that I should tell the medical staff of the OTP right away so I can receive or
be referred to prenatal care. I understand that there are ways to maximize the healthy course of my
pregnancy while I am taking methadone or buprenorphine.
Signature of Patient: ___________________________________________________ Date of Birth: ________________
Date: ________________ Witness: ______________________________________________________________________
Adapted from material in the public domain.161
3-37
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3C: Naltrexone
Chapter 3C gives an overview of naltrexone pharmacology and specifc guidance on
dosing for oral and injectable naltrexone.
The opioid receptor antagonist naltrexone was
synthesized in the 1960s to block the euphoric
effects of morphine.162 Oral naltrexone was
approved by the Food and Drug Administration
(FDA) in 1984 for the blockade of the effects of
exogenously administered opioids. Long-acting,
sustained-release opioid agonist preparations
have been investigated since the 1970s to
improve adherence over oral medications. In
2010, FDA approved injectable extended-release
naltrexone (XR-NTX) for preventing return to
opioid dependence after medically supervised
withdrawal.
Despite its potential advantages (e.g., no abuse
liability, no special regulatory requirements), oral
naltrexone is not widely used to treat opioid use
disorder (OUD) because of low rates of patient
acceptance, diffculty in achieving abstinence for
the necessary time before initiation of treatment,
and high rates of medication nonadherence.163
Before initiating either formulation of naltrexone,
patients must be opioid abstinent for an adequate
period of time after completing opioid with-
drawal. Medically supervised opioid withdrawal
can be conducted on an outpatient or inpatient
basis. The latter is often reserved for patients with
co-occurring substance use disorders (SUDs) or
medical or psychiatric illness.
There are several pharmacological approaches
to medically supervised withdrawal. Methadone
can be used for this purpose in opioid treatment
programs (OTPs) and hospital settings. Patients
in opioid withdrawal typically receive an indi-
vidualized dose between 20 mg and 30 mg per
day, gradually reduced over 6 days or more.
Buprenorphine can be used in an adequate dose
to lessen withdrawal symptoms and then reduced
gradually over several days or more. If an opioid
agonist is used for medically supervised withdraw-
al, an adequate interval of time following the last
dose must occur before naltrexone induction.
When it is not possible to use opioid agonists,
alpha-2 adrenergic agonists such as clonidine can
be used off label at doses from 0.1 mg to 0.3 mg
every 6 to 8 hours to treat symptoms.164
Formulations
Oral: Oral naltrexone is a 50 mg tablet of
naltrexone hydrochloride. It was approved
by FDA in 1984 for blockade of the effects of
exogenously administered opioids and in 1994
for alcohol dependence treatment. A Cochrane
review examined 13 randomized trials among
1,158 patients who were opioid dependent and
provided counseling. They were treated with or
without oral naltrexone. The review concluded
that oral naltrexone was not superior to
placebo or to no medication in treatment
retention or illicit opioid use reduction.165
XR-NTX: In 2006, FDA approved XR-NTX as
an intramuscular (IM) injection every 4 weeks
or once a month for the treatment of alcohol
dependence. In 2010, FDA approved XR-NTX for
the prevention of return to opioid dependence
following medically supervised withdrawal.
XR-NTX is a suspension of 380 mg naltrexone
embedded in microspheres made from a biode-
gradable copolymer that undergoes hydrolysis as
it absorbs water. XR-NTX requires refrigeration
and is supplied as a vial of dry powder along
with a separate vial of an aqueous diluent, which
providers combine just before use.166
XR-NTX is more effective than placebo167 or
no medication168 in reducing risk of return to
opioid use.169 A multisite randomized trial in the
United States started in residential treatment
3-38
Medications for Opioid Use Disorder TIP 63
programs found that buprenorphine treatment was
associated with lower rates of return to use during
24 weeks of postdischarge outpatient treatment
compared with XR-NTX,170 given the signifcant
proportion of patients who did not actually receive
XR-NTX because of challenges related to XR-NTX
induction. The same study found no signifcant
between-group differences in rates of return to use
when data were analyzed based solely on patients
who did begin assigned medications. Study
fndings may not generalize to outpatient settings,
where XR-NTX induction may be more diffcult
than in residential treatment settings.
One additional study merits mention. A 12-week
trial was conducted in Norway with 159 partic-
ipants who, at the time of random assignment
to XR-NTX or buprenorphine, had completed
medically supervised withdrawal or were already
opioid abstinent. XR-NTX was found to be non-
inferior to buprenorphine in terms of treatment
retention or reduction in illicit opioid use.171
Pharmacology
Naltrexone is a competitive mu-opioid receptor
antagonist with strong receptor affnity.
Naltrexone does not activate the mu-opioid
receptor and exerts no opioid effects. Unlike
opioid agonists, naltrexone will not alleviate
withdrawal symptoms, will not cause withdrawal
when stopped, and cannot be diverted.
If patients maintained on naltrexone use
opioid agonists, naltrexone can block their
effects—a key feature of its therapeutic effcacy.
However, because the interaction at the receptor
is competitive, the blockade can potentially be
overridden with high doses of opioids.
Taking naltrexone after recent use of opioids
can precipitate opioid withdrawal. Given its
strong affnity, naltrexone can displace other
opioids from the receptor. Patients must typically
wait 7 to 10 days after their last use of short-
acting opioids and 10 to 14 days after their last
use of long-acting opioids before taking their frst
dose of naltrexone.
Bioavailability
Oral: The gastrointestinal tract readily absorbs
oral naltrexone. Peak concentrations occur in 1 to
2 hours.172
XR-NTX: IM injection causes a transient peak
blood concentration 2 hours after injection and
another at 2 to 3 days after injection.173 About
14 days after injection, concentrations gradually
diminish, with measurable blood levels for more
than 1 month.
Both formulations are extensively metabolized
by the kidneys and liver, but without CYP450
enzyme system involvement. Unlike methadone
and buprenorphine, naltrexone has limited
potential drug–drug interactions. Its major
metabolite, 6-beta naltrexol, is also a mu-opioid
receptor antagonist. It is eliminated primarily by
the kidneys in the urine.174
Orally administered naltrexone has a half-life
of approximately 4 hours. Its primary me-
tabolite, 6-beta-naltrexol, is a weak mu-opioid
receptor antagonist with a half-life of approxi-
mately 12 hours.175
XR-NTX, or “depot naltrexone,” is encapsu-
lated in biodegradable polymer microspheres.
It provides opioid blockade by delivering
steady naltrexone concentrations for about
1 month.176 Elimination half-life is 5 to 10 days.
Repeated administration causes no accumulation
of naltrexone or its metabolites.
Dosing Considerations
XR-NTX
XR-NTX is indicated for the prevention of return
to opioid dependence following medically super-
vised opioid withdrawal. Appropriate patients
should have an adequate period of abstinence
with no signs of opioid withdrawal before XR-NTX
administration. Patients must be willing to receive
monthly IM injections. Become acquainted with
the FDA label for XR-NTX, which is available
online (https://dailymed.nlm.nih.gov/dailymed/
drugInfo.cfm?setid=cd11c435-b0f0-4bb9-ae78-
60f101f3703f).
3-39
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
•
•
•
•
Contraindications
Contraindications to receiving XR-NTX (as
well as to receiving oral naltrexone, with the
exception of hypersensitivity to the XR-NTX
suspension and diluent) include:177
• Current pain treatment with opioid analgesics.
• Current physiological opioid dependence.
• Current acute opioid withdrawal.
• Severe hepatic impairment.
• Naloxone challenge (Exhibit 3C.1) or oral
naltrexone dose causing opioid withdrawal
symptoms.
• History of hypersensitivity to naltrexone,
polylactide-co-glycolide, carboxymethylcellu-
lose, or any other components of the diluent.
Research suggests that patients who test positive
for current opioid use are not contraindicated
for XR-NTX induction as long as they pass the
naloxone challenge, indicating they are not opioid
dependent.178 In one study, patients being tran-
sitioned to XR-NTX using a 7-day detoxifcation
protocol could safely begin receiving XR-NTX
as long as they passed a naloxone challenge on
Day 8 of the protocol, even if they were unable
to completely refrain from using opioids during
the transition period.179,180 Patients who tested
positive for either methadone or buprenorphine
were excluded from enrollment in the study,
however.
Precautions and warnings
Discuss the risks and benefts of continuing
naltrexone with patients who become
pregnant while receiving naltrexone
treatment and whose OUD is in remission.
Unlike methadone and buprenorphine, nal-
trexone has been little researched in pregnant
populations.181,182
Patients are vulnerable to opioid overdose
death after completing the every-4-weeks or
once-monthly dosing period, missing a dose,
or stopping treatment. Trying to override
opioid blockade with high opioid doses may
cause overdose.
Patients may experience injection site
reactions including pain, tenderness, indura-
tion, swelling, erythema, bruising, or pruritus.
Severe injection site reactions may occur (e.g.,
cellulitis, hematoma, abscess, sterile abscess,
necrosis). Some cases may require surgical in-
tervention and may result in signifcant scarring.
(See the Chapter 3C Appendix for techniques to
reduce injection site reactions.) As with any IM
injection, use caution in patients with thrombo-
cytopenia or a coagulation disorder.
Precipitated opioid withdrawal can occur
in patients who used illicit opioids recently
or switched from an opioid agonist med-
ication. Symptoms may be severe enough
for hospitalization. To avoid precipitated
withdrawal from either formulation, patients
should typically stop use of short-acting opioid
agonists for 7 to 10 days and long-
acting agonists for 10 to 14 days.183 There is
also research on approaches to initiate XR-NTX
more quickly for patients physically dependent
on opioid agonists.184,185,186
Hepatitis has been associated with XR-NTX,
often in the presence of other potential causes
of hepatic toxicity (e.g., alcohol liver disease,
viral hepatitis). Monitor liver function tests
during treatment. Discontinue treatment in the
presence of acute hepatitis and severe liver
disease.187 Initiate or refer patients to treatment
for hepatitis.
• Use cautiously in patients with moderate-
to-severe renal impairment, because the
medication is eliminated primarily through
the kidneys.
• Hypersensitivity reactions can occur,
including rash, urticaria, angioedema, and
anaphylaxis.
• Monitor patients with OUD for depression
and suicidal ideation. Oral naltrexone use has
been occasionally associated with dysphoria,188
although it’s unclear whether this is a side
effect of the medication or a manifestation
of underlying depression or depressed mood
related to OUD.189 Monitor patients for depres-
sion, which is common with OUD.
• If a patient needs emergency pain
treatment, regional anesthesia or nonopioid
analgesics are alternatives to opioid analge-
sics. A patient who must have opioids for pain
treatment or anesthesia requires continuous
monitoring in an anesthesia care setting.
3-40
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3C.1. Naloxone Challenge
Use the naloxone challenge to assess lack of physical opioid dependence. Naloxone can be
administered via intravenous, subcutaneous, or IM routes to patients who report an adequate
period of opioid abstinence and have a negative opioid urine test (including morphine, methadone,
buprenorphine, and oxycodone). A negative naloxone challenge does not guarantee that the patient
will not experience precipitated opioid withdrawal upon naltrexone administration.190
Intravenous Administration
1. Draw 0.8 mg naloxone into a sterile syringe.
2. Inject 0.2 mg naloxone intravenously.
3. Wait 30 seconds for signs and symptoms of withdrawal. If withdrawal signs/symptoms are present,
stop the naloxone challenge and treat symptomatically.
4. If no withdrawal signs and symptoms are present and vital signs are stable, inject remaining
naloxone (0.6 mg) and observe for 20 minutes. Check the patient’s vital signs and monitor for
withdrawal.
5. If withdrawal signs and symptoms are present, stop the naloxone challenge and treat
symptomatically. The test can be repeated in 24 hours or the patient can be considered for opioid
agonist treatment.
6. If no withdrawal signs and symptoms are present* and oral naltrexone is the desired treatment
course, give the patient two tablets of 25 mg naltrexone (take one tablet on each of the next 2 days)
and a suffcient number of 50 mg naltrexone tablets (take one 50 mg tablet daily starting on the
third day) until they are able to fll their prescription for oral naltrexone. Skip to Step 8.
7. If no withdrawal signs and symptoms are present** and XR-NTX is the desired treatment course,
administer XR-NTX in the upper outer quadrant of the buttock, following package insert directions
(summarized below).
8. Instruct the patient about the risk of overdose and death if they use opioids to override the blockade.
Subcutaneous Administration
1. Inject 0.8 mg naloxone subcutaneously.
2. Wait 20 minutes while checking vital signs and observing for signs and symptoms of opioid
withdrawal.
3. If withdrawal signs and symptom are present, stop the naloxone challenge and treat
symptomatically. The test can be repeated in 24 hours or the patient can be considered for opioid
agonist treatment.
4. If no withdrawal signs and symptoms are present, follow Step 6 (for oral naltrexone treatment) or
Step 7 (for XR-NTX treatment) above.
* Optional: If withdrawal signs and symptoms are absent, administer 25 mg oral naltrexone and observe for 2 hours.
If the patient develops opioid withdrawal, treat symptomatically. If no withdrawal signs or symptoms are present
following the 25 mg naltrexone dose and oral naltrexone is the desired treatment course, give the patient one tablet
of 25 mg naltrexone to take the next day and 50 mg naltrexone tablets to take daily starting the day after.
** Optional: If withdrawal signs and symptoms are absent, administer 25 mg oral naltrexone and observe for 2
hours. If the patient develops opioid withdrawal, treat symptomatically and do not administer XR-NTX. This step is
recommended to minimize the likelihood of longer lasting precipitated withdrawal in patients given XR-NTX who took
buprenorphine recently (naloxone may not displace it from opioid receptors). This step can help identify a naltrexone
allergy before providing XR-NTX. If no withdrawal symptoms are present following the 25 mg naltrexone dose and
XR-NTX is the desired course, administer XR-NTX as described above.
Adapted from material in the public domain.191
3-41
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
Side efects
Possible side effects of XR-NTX include (see the
FDA label for a complete list https://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd
11c435-b0f0-4bb9-ae78-60f101f3703f):192
• Insomnia.
• Injection site pain.
• Hepatic enzyme abnormalities.
• Nasopharyngitis.
Assessment
Thorough assessment helps determine whether
naltrexone treatment is appropriate for a patient.
(Part 2 of this Treatment Improvement Protocol
[TIP] covers screening and assessment in more
detail.)
Patients who have been abstinent from
short-acting opioids (including tramadol) for
7 to 10 days or long-acting opioids (e.g.,
methadone, buprenorphine) for 10 to 14 days
can initiate naltrexone following assessment
that includes:
• Checking the state prescription drug moni-
toring program database.
• Taking the patient’s history.
− Conduct a medical, psychiatric, substance
use, and substance use treatment history.
can be used to assess withdrawal signs
(see “Resource Alert: Opioid Withdrawal
Scales”). The patient should not exhibit any
signs of opioid withdrawal before taking the
frst dose of naltrexone, to avoid precipitat-
ed withdrawal.
• Obtaining laboratory tests.
− Conduct drug and alcohol tests. Use
reliable urine tests for opioids (including
morphine, methadone, buprenorphine, and
oxycodone), benzodiazepines, cocaine, and
other drugs commonly used in the area.
Use a breathalyzer to estimate the patient’s
blood alcohol content.
− Conduct a pregnancy test. Naltrexone
is not recommended for OUD treatment
in pregnancy. Refer pregnant patients to
prenatal care.193
− Assess liver function. Obtain liver function
tests followed by periodic monitoring at 6-
or 12-month intervals during treatment.194
− Obtain kidney function tests (e.g., creati-
nine) for people who inject drugs.
− Conduct hepatitis and HIV tests. Hepatitis
B and C are common among patients
entering naltrexone treatment. HIV infection
is also prevalent. Everyone ages 15 to 65
should be tested at least once for HIV.
− Assess recent opioid use, including
frequency, quantity, type, route, and last
day of use. Confrm an adequate opioid
abstinence period.
− Establish OUD diagnosis.
− Assess for other SUDs, including those
that involve alcohol, benzodiazepines, or
stimulants.
Conducting a physical exam.
− Assess for signs and symptoms of intoxi-
cation. Do not give a frst dose to a patient
who is sedated or intoxicated. Assess and
treat him or her appropriately.
− Assess for evidence of opioid withdrawal
and physiological dependence. The
Clinical Opioid Withdrawal Scale (COWS)
or the Clinical Institute Narcotic Assessment
(CINA) Scale for Withdrawal Symptoms
RESOURCE ALERT
Opioid Withdrawal Scales
The COWS and other opioid withdrawal
scales from Annex 10 of the World Health
Organization’s Guidelines for the Psychosocially
Assisted Pharmacological Treatment of Opioid
Dependence can be downloaded from the
National Center for Biotechnology Information
website (www.ncbi.nlm.nih.gov/books
/NBK143183).
The CINA Scale for Withdrawal Symptoms is
also available online (www.ncpoep.org/wp
-content/uploads/2015/02/Appendix_7_Clinical
_Institute_Narcotic_Assessment_CINA_Scale
_for_Withdrawal_Symptoms.pdf).
3-42
Medications for Opioid Use Disorder TIP 63
Persons at higher risk, such as people who
use drugs by injection, should be tested
annually.195 Anyone who is injecting or
has ever injected drugs, even once, no
matter how long ago, should be tested for
hepatitis C, regardless of their intention
to seek treatment for SUD.196 The Centers
for Disease Control and Prevention recom-
mends hepatitis B vaccine for individuals
seeking treatment for SUDs.197
During assessment, discuss with patients the
risks and benefts of naltrexone and alternative
treatment approaches. Explore patients’ moti-
vation to initiate medication treatment and to
adhere to the dosing regimen. Start naltrexone
if the patient:
• Meets Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition, criteria for
OUD.
• Understands risks and benefts.
• Reports opioid abstinence for 7 to 10 days
(short acting) or 10 to 14 days (long acting).
• Reports no allergies to naltrexone or the
components of the XR-NTX preparation.
• Does not have a coagulation disorder.
• Will not soon require opioid analgesia.
• Has a negative pregnancy test.
• Has a negative urine opioid screen for
morphine, methadone, buprenorphine,
oxycodone, and other opioids.
• Is free of current opioid withdrawal signs
Inform patients of all their treatment options
and the settings in which they are available.
OTPs may be best for patients needing more
structure. Tailor decisions about which medica-
tion to use to patients’ medical and substance
use histories, patient preferences, and treatment
availability.
Pregnant women are not appropriate
candidates for XR-NTX treatment.
Potentially suitable candidates for XR-NTX
treatment include patients who:199
• Do not wish to take opioid agonists.
• Have been opioid abstinent for at least
1 week, have recently been or will soon be
released from controlled environments (e.g.,
incarceration, residential addiction treatment),
and do not wish to initiate (or are not able
to access) opioid agonist treatment. For
patients requesting opioid agonist treatment,
methadone or buprenorphine must be started
at much lower doses and increased much
more slowly than for opioid-tolerant patients
(see sections on methadone and buprenor-
phine dosing).
• Have not responded well to prior adequate
treatment with opioid agonist therapy.200
• Are part of an overall program with external
monitoring and signifcant, immediate external
consequences for lack of adherence (because
these patients [e.g., healthcare professionals,
and symptoms (Exhibit 3C.2).
• Has liver function test results that do not
indicate acute hepatitis or liver failure.
• Has a negative naloxone challenge result
(Exhibit 3C.1).
Patient selection
No evidence clearly predicts which patients are
best treated with XR-NTX versus other OUD
medications. A secondary analysis of the data
from a randomized trial of XR-NTX versus placebo
conducted in Russia found no signifcant baseline
predictors of successes among the 25 variables
examined, including demographics, clinical
severity, level of functioning, craving,
and HIV serostatus.198
EXHIBIT 3C.2. Signs and
Symptoms of Opioid
Withdrawal
Signs
Runny nose
Tearing
Yawning
Sweating
Tremor
Vomiting
Piloerection
Pupillary dilation
Symptoms
Skin crawling
Abdominal cramps
Temperature changes
Nausea
Vomiting
Diarrhea
Bone or muscle pain
Dysphoria
Craving for opioids
3-43
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
pilots, probationers, parolees] may show higher
rates of retention with XR-NTX because of
required external monitoring).201
• Have home locations or work schedules
making daily or almost-daily OTP visits
impossible or risky (e.g., job loss).
One study demonstrated that stable patients who
were able to taper to 8 mg or less of buprenor-
phine may be successfully started on XR-NTX
using a regimen consisting of a buprenorphine
taper and ancillary medications to palliate
withdrawal symptoms.202 The study employed
a hybrid outpatient and residential care model
and excluded patients who consistently tested
positive for illicit or nonprescribed opioids.
Informed consent
Inform all patients of the following basic
information:
• Their OUD diagnosis and the nature of the
disorder
• Risks and benefts of XR-NTX and other OUD
medications
• Risks and benefts of nonmedication treatments
Consider asking patients to sign a treatment
agreement form before starting treatment.
(See Appendix 3C for a sample treatment
agreement.) Document informed consent discus-
sions in the medical record.
Educate patients and their families about what
to expect from XR-NTX treatment (Exhibit
3C.3). A naltrexone medication guide should
be dispensed to patients with each injection.
Caution them about increased risk of overdose
if they stop treatment and return to illicit opioid
use or attempt to override the receptor blockade
of XR-NTX. Document education in the medical
record. Chapter 3C Appendix has a patient
education counseling tool for XR-NTX.
Use language and written materials
appropriate to each patient’s
comprehension level to ensure that he
or she understands the options and can
make informed decisions.
Initiating XR-NTX treatment
Storage and preparation
A pharmacy will send XR-NTX and its diluent in a
refrigerated package with two sets of administra-
tion needles (1.5 and 2 inches), a 1-inch prepara-
tion needle, and a needle protection device.
The XR-NTX microspheres are temperature
sensitive. When the carton arrives from the
pharmacy, store it in a refrigerator at 36 to 46
degrees Fahrenheit (2 to 8 degrees Celsius). The
refrigerator should have a working thermometer;
check the temperature regularly.
Do not freeze the carton or expose it to tem-
peratures above 77 degrees Fahrenheit (25
degrees Celsius). XR-NTX can be stored unrefrig-
erated for up to 7 days before administration.
Before preparing XR-NTX for administration,
keep it at room temperature for about 45
minutes. Examine the microspheres and diluent
to ensure that no particulate matter or discolor-
ation are present. Mix following FDA-approved
package insert directions, using the 1-inch
preparation needle. Resulting suspension should
be milky white, without clumps, and able to move
freely down the wall of the vial.
Two sets of needles of two different lengths are
shipped with the medication in case the frst
needle clogs before injection. Use the 1.5-inch
needle for lean patients and the 2-inch needle
for patients with more subcutaneous tissue
overlying the gluteal muscle. The longer needle
helps ensure that the injection reaches the
muscle. Inject patients with average body habitus
with either needle.
Administration
Administer XR-NTX every 4 weeks or once
a month as a 380 mg IM gluteal injection.
Alternate buttocks for each 4-week injection.
Given the risk of severe injection site reactions,
FDA requires a risk evaluation and mitigation
strategy (www.vivitrolrems.com) for XR-NTX
including a patient counseling tool, a patient
medication guide, and a visual aid to reinforce
proper XR-NTX injection technique.
3-44
Medications for Opioid Use Disorder TIP 63
•
•
•
•
•
•
•
•
•
•
EXHIBIT 3C.3. Key Points of Patient Education for XR-NTX
•
•
•
•
Do not use any opioids in the 7 to 10 days (for
short acting) or 10 to 14 days (for long acting)
before starting XR-NTX, to avoid potentially
serious opioid withdrawal symptoms. Opioids
include:
- Heroin.
- Prescription opioid analgesics (including
tramadol).
- Cough, diarrhea, or other medications that
contain codeine or other opioids.
- Methadone.
- Buprenorphine.
Seek immediate medical help if symptoms of
allergic reaction or anaphylaxis occur, such as:
- Itching.
- Swelling.
- Hives.
- Shortness of breath.
- Throat tightness.
Do not try to override the opioid blockade with
large amounts of opioids, which could result in
overdose.
Understand the risk of overdose from using
opioids near the time of the next injection, after
missing a dose, or after stopping medications.
Report injection site reactions including:
- Pain.
- Hardening.
- Lumps.
Follow-up care afer frst dose
Examine patients within a week of administer-
ing their frst XR-NTX dose. It can be clinically
benefcial to maintain weekly contact in the frst
month to:
• Provide supportive counseling.
• Assess ongoing drug or alcohol use.
• Monitor side effects.
• Obtain drug testing.
• Follow up on status of referrals to
counseling or other services.
- Blisters.
- Blackening.
- Scabs.
- An open wound.
Some of these reactions could require surgery to
repair (rarely).
Report signs and symptoms of hepatitis (e.g.,
fatigue, abdominal pain, yellowing skin or eyes,
dark urine).
Report depression or suicidal thoughts. Seek
immediate medical attention if these symptoms
appear.
Seek medical help if symptoms of pneumonia
appear (e.g., shortness of breath, fever).
Inform providers of naltrexone treatment,
as treatment differs for various types of
pneumonia.
Inform all healthcare professionals of XR-NTX
treatment.
Report pregnancy.
Inform providers of any upcoming medical
procedures that may require pain medication.
Understand that taking XR-NTX may result in
diffculty achieving adequate pain control if
acute medical illness or trauma causes severe
acute pain.
Wear medical alert jewelry and carry a medical
alert card indicating you are taking XR-NTX. A
patient wallet card or medical alert bracelet can
be ordered at 1-800-848-4876.
Patients who test the opioid blockade of XR-NTX
may discontinue use because of the blocking of
the euphoric effects of illicit opioids.203 Patients
who miss a dose can restart medication (use
procedures outlined earlier in this section) after
an adequate period of opioid abstinence (7 to
14 days).
The TIP expert panel cautions that,
based on current data, arbitrary time
limits on XR-NTX are inappropriate.
3-45
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
See Chapter 3E for information on the manage-
ment of patients taking naltrexone in offce-
based treatment settings.
Duration of treatment
Barring contraindications, patients should
continue taking XR-NTX as long as they
beneft from it and want to continue. Data are
limited on the long-term effectiveness of XR-NTX
compared with methadone or buprenorphine.
Treatment discontinuation
When patients wish to discontinue naltrexone,
engage in shared decision making and explore:
• Their reasons for wanting to discontinue.
• The risks and benefts of discontinuing.
• Problem-solving strategies that can help them
make an informed choice.
• Their appropriateness for buprenorphine or
methadone treatment.
Discourage patients who are not yet stable
from discontinuing treatment, because of the
high rate of return to illicit opioid use and the
increased chance of overdose death.
Signs that a patient may be ready to discontinue
medication include:204
• Sustaining illicit drug abstinence over time.
• Having stable housing and income.
RESOURCE ALERT
• Having no legal problems.
• Having substantially reduced craving.
• Attending counseling or mutual-help groups.
Patients who discontinue should have a
recovery plan that may include monitoring as
well as adjunctive counseling and recovery
support. If they return to opioid use, encourage
them to return for assessment and reentry into
treatment.
Given the high risk of return to illicit opioid
use, offer patients information about opioid
overdose prevention and a naloxone pre-
scription they can use in case of overdose.
When patients stop using naltrexone, they
will have no tolerance for opioids. Their risk of
overdose is very high if they use again. For more
information, see the SAMHSA Opioid Overdose
Prevention Toolkit (https://store.samhsa.gov/
product/Opioid-Overdose-Prevention-Toolkit/
SMA18-4742).
Rapid naltrexone induction
Patients with OUD need to discontinue
opioids and wait 7 to 14 days after last
opioid use (including any given for with-
drawal treatment) before receiving XR-NTX.
As described above, they can do so through
medically supervised withdrawal in a controlled
environment, such as an inpatient unit, residen-
tial addiction treatment program, correctional
facility, or hospital, or on an outpatient basis.
Financial issues and managed care constraints
may infuence patients’ access to controlled
treatment environments. The alternative—
abstaining long enough after outpatient
medically supervised withdrawal—is challeng-
ing. Thus, various approaches to rapid naltrexone
induction have been developed205 and more
recently refned in research settings.206,207,208
Consider rapid induction in specialty addiction
treatment programs, not general medical
settings. It may be hard for providers in general
medical settings to start XR-NTX successfully
with patients who need medically supervised
opioid withdrawal. Rapid induction approaches
are likely beyond the scope of general outpatient
Patient and Family Educational
Resources
Decisions in Recovery: Treatment for Opioid
Use Disorder offers information for patients on
the use of medications for OUD (https://store
.samhsa.gov/product/SMA16-4993).
Medication-Assisted Treatment for Opioid
Addiction: Facts for Families and Friends offers
information for family and friends (https://portal.
ct.gov/-/media/DMHAS/Opioid-Resources/
MATInfoFamilyFriendspdf.pdf).
3-46
Medications for Opioid Use Disorder TIP 63
settings. However, patients can successfully
initiate XR-NTX in a general outpatient medical
setting if they:
• Have been abstinent for suffcient time and
pass the naloxone challenge.
• Started taking XR-NTX elsewhere and are due
for the next injection.
One randomized trial compared two approaches
to starting XR-NTX on an outpatient basis. This
study assigned adults dependent on opioids
to either a standard 14-day buprenorphine-
assisted opioid withdrawal or more rapid 7-day
oral naltrexone-assisted opioid withdrawal.209
Naltrexone-assisted withdrawal was conducted
over 7 days. It included 1 day of buprenorphine
administration; 1 day with ancillary medications
including clonidine and clonazepam but no
buprenorphine; followed by 4 days of ancillary
medications and increasing daily doses of oral
naltrexone (starting with 1 mg, 3 mg, 12 mg,
and 25 mg); and concluding on day 7 with
XR-NTX administration. Buprenorphine-assisted
withdrawal consisted of a 7-day buprenorphine
taper followed by the recommended 7 days
without opioids. The naltrexone-assisted
withdrawal group was signifcantly more
likely to begin XR-NTX compared with the
buprenorphine-assisted withdrawal group (56.1
percent versus 32.7 percent, respectively). This
type of approach, which must be conducted
with careful daily monitoring, is used in some
residential programs and may prove to be a
useful approach to outpatient XR-NTX induction
in specialty programs. More discussion on rapid
induction approaches is available in Implementing
Antagonist-Based Relapse Prevention Treatment
for Buprenorphine-Treated Individuals,210
available online (http://pcssmat.org/wp-content
/uploads/2015/02/PCSSMAT-Implementing
-Antagonist-with-Case.Bisaga.CME_.pdf).
Oral Naltrexone
The effectiveness of oral naltrexone is limited,
given poor adherence and the requirement of 7
to 14 days of opioid abstinence before initiation.
During this waiting period, patients may drop
out of care. One study found signifcantly lower
patient retention in treatment after incarcera-
tion for patients treated with oral naltrexone
compared with methadone.211
Oral naltrexone blocks opioid-induced euphoria
for only a day or two. When patients stop taking
it, risks of return to opioid use and overdose
increase.
The TIP expert panel doesn’t recommend
using oral naltrexone except in the limited
circumstances described in the following
sections. This view is in keeping with expert
reviews for the United Kingdom’s National
Health Service,212 a clinical practice guideline
published by the Department of Veterans Affairs
and Department of Defense,213 and a Cochrane
review.214
Indications and contraindications,
precautions and warnings, side efects, and
assessment.
All are similar to those for XR-NTX, save issues
specifc to suspension/diluent contents and the
injection itself.
Patient Selection
In limited circumstances, oral naltrexone may
be considered after the risks and benefts, as
well as alternative treatments, are discussed with
the patient. Examples include:
• Patients who cannot afford XR-NTX but
wish to take an opioid receptor antagonist.
• Patients with high levels of monitoring and
negative consequences for nonadherence,
such as healthcare professionals who may
not be permitted to have opioid agonist
treatment.215,216
The TIP expert panel does not
recommend that payers require
patients to fail oral naltrexone before
providing access to XR-NTX, given the
risk of unintentional overdose death if
the patient returns to illicit opioid use.
3-47
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
•
•
•
•
•
•
Patients leaving controlled environments
(e.g., prisons, hospitals, inpatient addiction re-
habilitation) who may beneft from medication
to prevent return to illicit drug use but cannot
or will not take XR-NTX and do not wish to be
treated with (or do not have access to) opioid
agonists.
Patients who have taken methadone or ex-
tensively used heroin are especially poor oral
naltrexone candidates.217
Dosing
Following a negative naloxone challenge, the
frst oral dose of naltrexone can be 25 mg (half
of the usual daily naltrexone maintenance dose).
This reduces risk of a more severe precipitated
opioid withdrawal than could occur with a full
50 mg dose. This lower dose may also reduce
nausea associated with the frst oral naltrexone
dose. The dose can be increased to 50 mg daily
on the second day.
To increase adherence, arrange for directly
observed administration of oral naltrexone.
This is more feasible if patients who tolerate a
daily dose of 50 mg are switched to a 3-days-
per-week regimen for a total weekly dose of 350
mg (e.g., administer 100 mg on Monday and
Wednesday and 150 mg on Friday). A member
of the patient’s social network (e.g., spouse) may
also directly observe therapy.
Duration of treatment
The optimal length of treatment with oral
naltrexone is not known. In general, the
longer patients take an effective medication,
the better their outcomes.
Use of illicit opioids during treatment with oral
naltrexone is a cause of concern and may be a
precursor to treatment discontinuation.218 Some
patients will initially test the opioid blockade
with illicit opioids and then discontinue opioid
use. However, others will continue using illicit
opioids.219
If patients continue to test the blockade,
immediately discuss alternative treatment
plans that include:
• Increased counseling.
• Switching to XR-NTX.
• Closer monitoring.
• Directly observed oral naltrexone therapy.
• Residential treatment.
• Assessment for the appropriateness of
buprenorphine or methadone.
Naltrexone Dosing Summary
XR-NTX
Before administering XR-NTX, keep it at room
temperature for about 45 minutes.
Use the correct needle length to ensure the
injection is in the gluteal muscle.
− Use the 2-inch needle for patients with
more subcutaneous tissue and the 1.5-inch
needle for patients with less adipose tissue.
− Use either length in patients with normal
body habitus.
Use proper aseptic technique.
Use proper gluteal IM injection technique.
Never inject intravenously or subcutaneously.
Repeat the injection every 4 weeks or once
per month.
Oral Naltrexone
• Use in limited circumstances after discussing
risks and benefts, as well as alternative
treatment options, with the patient.
• Do the naloxone challenge.
• The frst oral naltrexone dose should be 25 mg.
• The dose can be increased on the second day
to 50 mg daily if necessary.
• If desired, switch patients who tolerate a daily
dose of 50 mg to a 3-days-per-week regimen
for a total weekly dose of 350 mg.
3-48
Medications for Opioid Use Disorder TIP 63
Chapter 3C Appendix
Sample XR-NTX Treatment Agreement
This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care. Healthcare
professionals should use their judgment in interpreting this form and applying it in the circumstances of their individual
patients and practice arrangements. The information provided in this form is provided “as is” with no guarantee as to its
accuracy or completeness.
TREATMENT AGREEMENT
I agree to accept the following treatment agreement for extended-release injectable naltrexone (XR-NTX)
offce-based opioid use disorder treatment:
1. The risks and benefts of XR-NTX treatment have been explained to me, and I understand the information provided.
2. The risks and benefts of other treatment for opioid use disorder (including methadone, buprenorphine, and
nonmedication treatments) have been explained to me.
3. I will be on time to my appointments and respectful to the offce staff and other patients.
4. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical
problems.
5. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider.
6. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance
so that my pain will be adequately treated.
7. If I miss a scheduled appointment for my XR-NTX injection, I understand that I should reschedule the
appointment as soon as possible because it is important to receive the medication on time to reduce the risk of
opioid overdose should I return to use.
8. If I come to the offce intoxicated, I understand that my healthcare provider will not see me.
9. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in
treatment termination from the clinic.
10. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will
count as a positive drug test.
11. I understand that initially I will have weekly offce visits until my condition is stable.
12. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug
tests in a row.
13. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me.
14. I understand that people have died trying to overcome the opioid blockade by taking large amounts of opioids.
15. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to follow
my healthcare provider’s recommendations for additional counseling and/or for help with other problems.
16. I understand that there is no fxed time for being on XR-NTX and that the goal of treatment is for me to stop
using all illicit drugs and become successful in all aspects of my life.
17. I understand that my risk of overdose increases if I go back to using opioids after stopping XR-NTX.
18. I have been educated about the other two FDA-approved medications used to treat opioid use disorder,
methadone and buprenorphine, and I prefer to receive treatment with XR-NTX.
19. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting
XR-NTX treatment and have been informed about methods for preventing pregnancy.
20. I have been informed that if I become pregnant during naltrexone treatment, I should inform my provider and
have a discussion about the risks and benefts of continuing to take XR-NTX.
Other specifc items unique to my treatment include:
Patient’s Name (print): _____________________________________________________
Patient’s Signature: ________________________________________________________ Date: ____________________
This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is updated
periodically; the most current version of the agreement is available online (www.asam.org/docs/default-source/advocacy/sample
-treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn=0).
Adapted with permission.220
3-49
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
•
•
•
Intense pain
The area feels hard
Large areas of swelling
Lumps
•
•
•
Blisters
Open wound
Dark scab
•
•
Stomach area pain lasting more than a few days
Dark urine
•
•
Yellowing of the whites of eyes
Tiredness
Patient Counseling Tool for XR-NTX
Patient Counseling Tool
VIVITROL® (naltrexone for extended-release injectable suspension)
Risk of sudden opioid withdrawal during initiation and re-initiation of VIVITROL
Using any type of opioid including street drugs, prescription pain medicines, cough, cold or diarrhea medicines
that contain opioids, or opioid dependence treatments buprenorphine or methadone, in the 7 to 14 days before
starting VIVITROL may cause severe and potentially dangerous sudden opioid withdrawal.
Risk of opioid overdose
Patients may be more sensitive to the effects of lower amounts of opioids:
• After stopping opioids (detoxifcation) • If a dose of VIVITROL is missed
• When the next VIVITROL dose is due • After VIVITROL treatment stops
Patients should tell their family and people close to them about the increased sensitivity to opioids and the
risk of overdose even when using lower doses of opioids or amounts that they used before treatment. Using
large amounts of opioids, such as prescription pain pills or heroin, to overcome effects of VIVITROL can lead to
serious injury, coma, and death.
Risk of severe reactions at the injection site
Remind patients of these possible symptoms at the injection site:
Some of these injection site reactions have required surgery.
Tell your patients to contact a healthcare provider if they have any reactions at the injection site.
Risk of liver injury, including liver damage or hepatitis
Remind patients of the possible symptoms of liver damage or hepatitis.
Patients may not feel the therapeutic effects of opioid-containing medicines for pain, cough or
cold, or diarrhea while taking VIVITROL.
Patients should carry written information with them at all times to alert healthcare providers that they are
taking VIVITROL, so they can be treated properly in an emergency.
A Patient Wallet Card or Medical Alert Bracelet can be ordered from: 1-800-848-4876, Option #1.
PLEASE SEE PRESCRIBING INFORMATION AND MEDICATION GUIDE.
Alkermes® and VIVITROL® are registered trademarks of Alkermes, Inc.
©2013 Alkermes, Inc.
All rights reserved VIV-001317 Printed in U.S.A
w w w.vivitrol.com
Available online (www.vivitrolrems.com/content/pdf/patinfo-counseling-tool.pdf).
Reprinted with permission.221
3-50
Medications for Opioid Use Disorder TIP 63
Key Techniques for Reducing Injection Site Reactions222
To reduce severe injection site reactions when administering XR-NTX via intramuscular injection, use
the following techniques:
• Use one of the administration needles provided with the XR-NTX kit to ensure that the
injection reaches the gluteal muscle. Use the 2-inch needle for patients who have more subcuta-
neous adipose tissue. Use the 1.5-inch needle for patients with less subcutaneous adipose tissue.
Either needle is appropriate for use with patients who have average amounts of subcutaneous
adipose tissue.
• Use aseptic technique when administering intramuscularly. Using a circular motion, clean the
injection site with an alcohol swab. Let the area dry before administering the injection. Do not
touch this area again before administration.
• Use proper deep intramuscular injection technique into the gluteal muscle. XR-NTX must not
be injected intravenously, subcutaneously, or into adipose tissue. Accidental subcutaneous injection
may increase the risk of severe injection site reactions.
− Administer the suspension by deep intramuscular injection into the upper outer quadrant
of gluteal muscle, alternating buttocks per monthly injection.
− Remember to aspirate for blood before injection. If blood aspirates or the needle clogs, do
not inject. Change to the spare needle provided in the package and administer into an adjacent
site in the same gluteal region, again aspirating for blood before injection.
− Inject the suspension in a smooth, continuous motion.
A patient counseling tool is available to help you counsel your patients before administration about
the serious risks associated with XR-NTX.
The above information is a selection of key safety information about the XR-NTX injection. For
complete safety information, refer to the directions for use and the prescribing information provided
in the medication kit. You can also obtain this information online (www.vivitrolrems.com) or by calling
1-800-VIVITROL.
Available online (www.vivitrolrems.com/content/pdf/patinfo-injection-poster.pdf).
3-51
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
•
•
•
•
•
•
Chapter 3D: Buprenorphine
Chapter 3D is an overview of buprenorphine pharmacology and specifc dosing guidance
for sublingual and buccal formulations and buprenorphine implants and injections.
Buprenorphine and buprenorphine/naloxone
formulations are effective treatments for opioid
use disorder (OUD). Numerous clinical studies
and randomized clinical trials have demonstrated
buprenorphine’s effcacy in retaining patients
in treatment and reducing illicit opioid use
compared with treatment without medication
and medically supervised withdrawal.223,224,225
Other research has associated it with reduction
in HIV risk behavior and risk of overdose death,
and its effectiveness has been shown in primary
care settings.226,227,228,229,230 Buprenorphine is on
the World Health Organization (WHO) list of
essential medications.231
The Treatment Improvement Protocol (TIP)
expert panel recommends offering the option
of Food and Drug Administration (FDA)-
approved buprenorphine formulations to
appropriate patients with OUD, considering
patient preferences for and experience with
other medications or no medication. These
recommendations align with Department of
Veterans Affairs guidelines.232
Formulations
History of Approvals
FDA originally approved buprenorphine for
analgesia. Formulations for OUD treatment were
approved in:
2002: Sublingual buprenorphine/naloxone
sublingual tablets (Suboxone); sublingual
buprenorphine tablets (Subutex). The manu-
facturer discontinued the tablet formulations
of both from the U.S. market after the flm’s
approval, but generic tablet formulations are
still available (Exhibit 3A.5, Chapter 3A).
2010: Buprenorphine/naloxone sublingual flms.
2013: Buprenorphine/naloxone sublingual
tablets (Zubsolv).233
2014: Buprenorphine/naloxone buccal flms
(Bunavail).234
2016: Buprenorphine implants (Probuphine).
2017: Buprenorphine extended-release
injection (Sublocade).
2018-2019: Additional dosage strengths of
buprenorphine/naloxone sublingual flms.
FDA approved generic buprenorphine and
buprenorphine/naloxone formulations based
on evidence that they produce similar (within
90 percent confdence intervals) bioequivalence
on pharmacokinetic measures, such as peak
serum concentration, compared with the original
sublingual buprenorphine/naloxone product.
The 2013 and 2014 branded formulations
have greater bioavailability than Suboxone,
meaning they deliver more buprenorphine
to the bloodstream, thus achieving the same
effect as the original product with lower
doses. For example, 5.7 mg/1.4 mg of Zubsolv
and 4.2 mg/0.7 mg of Bunavail provide the
same buprenorphine exposure as 8 mg/2 mg
of Suboxone.
Opioid treatment programs (OTPs)
may administer or dispense
buprenorphine, but only providers
with Substance Abuse and Mental
Health Services Administration
(SAMHSA) waivers can prescribe
buprenorphine for OUD. See “Resource
Alert: How To Obtain a Waiver To
Prescribe Buprenorphine” in Chapter
3A of this TIP.
3-52
Medications for Opioid Use Disorder TIP 63
Exhibit 3D.1 lists product strengths and recom-
mended once-daily maintenance doses. For
simplicity, dosing information here refers to
sublingual Suboxone or generic equivalents.
An 8 mg/2 mg dosage of sublingual Suboxone
is equivalent to 5.7 mg/1.4 mg of sublingual
Zubsolv and 4.2 mg/0.7 mg of buccal Bunavail.
Patients who switch formulations may experience
clinically signifcant plasma concentration changes
that may require dose adjustments; bioavail-
ability is similar, but not identical, between
formulations.
Implants
In 2016, FDA approved buprenorphine
implants for OUD maintenance treatment in
patients who have achieved sustained clinical
stability (e.g., periods of abstinence, minimal or
no desire to use illicit opioids, stable housing,
social support) while taking no more than 8
mg of Suboxone or generic equivalents. The
implants are a set of four rods, each 2.5 mm in
diameter and 26 mm in length. Each rod contains
the equivalent of 80 mg of buprenorphine
hydrochloride. The implants are for
EXHIBIT 3D.1. Buprenorphine Transmucosal Products for OUD
Treatment
PRODUCT NAME/
ACTIVE INGREDIENT
ROUTE OF
ADMINISTRATION/
FORM
AVAILABLE
STRENGTHS
RECOMMENDED ONCE-
DAILY MAINTENANCE
DOSE
Bunavail235
• Buprenorphine hydrochloride
• Naloxone hydrochloride
Buccal flm 2.1 mg/0.3 mg
4.2 mg/0.7 mg
6.3 mg/1 mg
Target: 8.4 mg/1.4 mg
Range: 2.1 mg/0.3 mg to
12.6 mg/2.1 mg
Generic combination product236,237
• Buprenorphine hydrochloride
• Naloxone hydrochloride
Sublingual tablet,
flm
2 mg/0.5 mg
4 mg/1 mg
8 mg/2 mg
12 mg/3 mg
Target: 16 mg/4 mg
Range: 4 mg/1 mg to
24 mg/6 mg*
Generic monoproduct238,239
• Buprenorphine hydrochloride
Sublingual tablet 2 mg
8 mg
Target: 16 mg
Range: 4 mg to 24 mg*
Suboxone240,241
• Buprenorphine hydrochloride
• Naloxone hydrochloride
Sublingual flm 2 mg/0.5 mg
4 mg/1 mg
8 mg/2 mg
12 mg/3 mg
Target: 16 mg/4 mg
Range: 4 mg/1 mg to
24 mg/6 mg*
Zubsolv242,243
• Buprenorphine hydrochloride
• Naloxone hydrochloride
Sublingual tablet 0.7 mg/0.18 mg
1.4 mg/0.36 mg
2.9 mg/0.71 mg
5.7 mg/1.4 mg
8.6 mg/2.1 mg
11.4 mg/2.9 mg
Target: 11.4 mg/2.9 mg
Range: 2.9 mg/0.71 mg
to 17.2 mg/4.2 mg
*Dosages above 24 mg buprenorphine or 24 mg/6 mg buprenorphine/naloxone per day have shown no clinical
advantage.244,245
Adapted from material in the public domain.246
3-53
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
subdermal insertion on the inside of the upper
arm and provide 6 months of buprenorphine.
The implants must be removed after 6 months.
Peak buprenorphine plasma concentrations
occur 12 hours after implant insertion, slowly
decrease, and reach steady-state concentrations
in about 4 weeks. Steady-state concentrations
are comparable to trough buprenorphine plasma
levels produced by daily sublingual buprenor-
phine doses of 8 mg or less. Implant effective-
ness lasts up to 6 months.
Injectables
In November 2017, FDA approved extended-
release (monthly) subcutaneous injectable
buprenorphine for moderate-to-severe
OUD treatment among patients who initiated
treatment with transmucosal buprenorphine,
followed by at least 7 days of dose adjustment.
It is available in two doses, 300 mg/1.5 mL and
100 mg/0.5 mL. Both are stored refrigerated
in preflled syringes with safety needles and
administered by subcutaneous injection in the
abdomen. The frst two monthly doses recom-
mended are 300 mg each followed by a 100 mg
monthly maintenance dose. Peak buprenorphine
concentrations occur about 24 hours after the
injection. Steady state is achieved after 4 to 6
months. After discontinuation, patients may have
detectable plasma levels of buprenorphine for
12 months or longer. Duration of detection in
urine is not known.247
Pharmacology
Buprenorphine, an opioid receptor partial
agonist, is a schedule III controlled medication
derived from the opium alkaloid thebaine.
Through cross-tolerance and mu-opioid receptor
occupancy, at adequate doses, buprenorphine
reduces opioid withdrawal and craving and
blunts the effects of illicit opioids.
Buprenorphine binds tightly to the mu-opioid
receptor because of its particularly high
receptor affnity. This prevents other opioids
with lower affnity (e.g., heroin) from binding.
The net result is a blunting or blocking of the
euphoria, respiratory depression, and other
effects of these opioids.
Buprenorphine has less potential to cause
respiratory depression, given its ceiling effect.
As a partial agonist, buprenorphine’s maximum
effect on respiratory depression is more limited
than full agonists. Once reaching a moderate
dose, its effects no longer increase if the dose is
increased.248,249,250
There is wide individual variability in bu-
prenorphine pharmacokinetics. For example,
the mean time to maximum plasma buprenor-
phine concentration after a single sublingual
dose ranges from 40 minutes to 3.5 hours.251
Thus, after providing the frst dose of buprenor-
phine, wait at least 2 hours to decide whether a
second dose is necessary.
Buprenorphine has a long elimination half-life,
which varies from 24 to 69 hours252 with a mean
half-life of 24 to 42 hours.253 It dissociates slowly
from the receptor.
Buprenorphine can be safely dosed (even at
double the stabilized dose) less than daily.254
For example, a patient stabilized on 12 mg of
buprenorphine/naloxone daily can be treated
with 24 mg every other day or 24 mg on
Monday/Wednesday and 36 mg on Friday. Such
schedules reduce travel burden for patients who
need or want supervised dosing at an OTP or
a clinic. Such schedules may also be useful for
patients who must spend weekends in jails that
disallow buprenorphine dosing.
Bioavailability
Buprenorphine has poor oral bioavailabil-
ity compared with sublingual and buccal
bioavailability. Naloxone, a short-acting
mu-opioid receptor antagonist, has very poor
oral, sublingual, and buccal bioavailability but
is absorbed when injected or snorted. The
addition of naloxone decreases buprenorphine’s
potential for misuse. In the Suboxone formu-
lation of buprenorphine/naloxone, the ratio of
3-54
Medications for Opioid Use Disorder TIP 63
•
buprenorphine to naloxone is 4:1. The ratio
of buprenorphine to naloxone varies across
products, as the absorption of both active ingre-
dients is different for buccal versus sublingual
flms versus tablets.
Buprenorphine/naloxone transmucosal
products are abuse-deterrent formulations,
although they can still be misused. When a
patient takes these formulations as prescribed,
he or she absorbs buprenorphine but only a
biologically negligible amount of naloxone. But if
crushed or dissolved for intranasal or intravenous
(IV) misuse, both medications are bioavailable.
Naloxone then blunts the immediate opioid
agonist effects of buprenorphine. It also induces
opioid withdrawal in people who are physically
dependent on opioids. This reduces misuse
liability compared with transmucosal formulations
with buprenorphine alone.255,256
Subdermal buprenorphine implants release bu-
prenorphine in steady concentrations over 6
months. These concentrations are approximately
equivalent to 8 mg or less of the buprenorphine
sublingual formulations. Once implanted, these
rods are unlikely to be diverted.
Extended-release buprenorphine for subcuta-
neous injection releases buprenorphine over
at least a 1-month period. After injection, an
initial buprenorphine plasma level peaks around
24 hours and then slowly declines to a plateau.
With monthly injections, steady state is reached
at 4 to 6 months.257
Metabolism and Excretion
Buprenorphine:258,259
• Is highly plasma bound.
• Crosses the blood–brain barrier readily
because of its high lipid solubility.
• Is excreted in urine and feces.
• Has only one known pharmacologically active
metabolite: norbuprenorphine.
Be aware of potential CYP450 3A4 inducers,260
substrates, and inhibitors while monitoring
for potential drug–drug interactions (see
the “Drug Interactions” section below).
Buprenorphine undergoes metabolism in the
liver primarily by cytochrome P450 (CYP450) 3A4
enzymes. Coadministration of other medications
metabolized along this pathway can affect the
rate of buprenorphine metabolism.
Buprenorphine has fewer clinically relevant
drug interactions than methadone in general.
For detailed explanations of metabolism and
excretion, see the package inserts for each
buprenorphine product.
Dosing Considerations
Buprenorphine is used for the treatment of OUD.
Formulations are available as sublingual tablets
and flm, buccal flm, implants, and extended-
release injection (Exhibit 3A.5 in Chapter 3A of
this TIP).
Contraindications
Buprenorphine is contraindicated in patients
who are allergic to it. Patients with true allergic
reactions to naloxone should not be treated
with the combination buprenorphine/naloxone
product. Allergy to naloxone is infrequent.
Some patients may falsely or mistakenly claim an
allergy to naloxone and request buprenorphine
monoproduct. Carefully assess such claims and
explain the differences between an allergic
reaction and symptoms of opioid withdrawal
precipitated by buprenorphine or naloxone;
the monoproduct has more abuse liability than
buprenorphine/naloxone.261
Precautions and Warnings
Respiratory depression and overdoses
are uncommon in adults, but they do
happen.262 Most fatal overdoses involve IV
buprenorphine misuse or concurrent central
nervous system depressant use, including high
doses of benzodiazepines, alcohol, or other
3-55
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
•
•
sedatives.263,264 However, fatal overdoses have
been reported in opioid-naïve patients treated
with 2 mg buprenorphine for pain.265 Exhibit
3D.2 summarizes the management of patients
with preexisting respiratory impairment.
Unintentional pediatric exposure can be life
threatening or fatal.266 Thus, emphasize safe
storage of medication, and teach patients to
remove any buprenorphine found in a child’s
mouth immediately (even if it was only a
partial tablet or flm). Call 9-1-1 so the child
can go to the nearest emergency department
for immediate medical attention.
Cases of hepatitis and liver failure exist
but often involve predisposing hepatic
risk factors, such as preexisting liver enzyme
abnormalities, hepatitis B or C infections, and
use of other potentially hepatotoxic drugs
or IV drugs. A multisite randomized trial of
hepatic effects in patients taking methadone
or buprenorphine found no evidence of liver
damage in the frst 6 months of treatment.
The authors concluded that prescribing these
medications should not cause major concern
for liver injury.267 Exhibit 3D.2 summarizes man-
agement of patients with hepatic impairment.
EXHIBIT 3D.2. Medication Management for Patients With Respiratory
or Hepatic Impairment
CONTRAINDICATION/CAUTION MANAGEMENT
Compromised respiratory function
For example, chronic obstructive
pulmonary disease, decreased respiratory
reserve, hypoxia, hypercapnia (abnormally
elevated blood levels of carbon dioxide),
preexisting respiratory depression.
•
•
•
•
•
•
Prescribe with caution; monitor closely.
Warn patients about the risk of using benzodiazepines
or other depressants while taking buprenorphine.270
Support patients in their attempts to discontinue
tobacco use.
Hepatic impairment
Mild impairment (Child-Pugh score of 5–6)271 No dose
adjustment needed.
Moderate impairment (Child-Pugh score of 7–9):272
Combination products are not recommended; they may
precipitate withdrawal.
*Use combination products cautiously for maintenance
treatment in patients who’ve been inducted with a
monoproduct;273,274 monitor for signs and symptoms of
buprenorphine toxicity or overdose.275 Naloxone may
interfere with buprenorphine’s effcacy.276,277
Severe impairment (Child-Pugh score of 10–15):278 Do
not use the combination product.279 For monoproduct,
consider halving the starting and titration doses used in
patients with normal liver function; monitor for signs and
symptoms of toxicity or overdose caused by increased
buprenorphine levels.280
Buprenorphine and naloxone are
extensively metabolized by the liver.
Moderate-to-severe impairment results
in decreased clearance, increased overall
exposure to both medications, and
higher risk of buprenorphine toxicity
and precipitated withdrawal from
naloxone. These effects have not been
observed in patients with mild hepatic
impairment.268,269
*Moderate-to-severe impairment results in much more reduced clearance of naloxone than of buprenorphine. Nasser
et al.281 found that moderate impairment doubled or tripled exposure (compared with subjects with no or mild
impairment) for both medications. In subjects with severe impairment, buprenorphine exposure was also two to three
times higher; naloxone exposure increased more than tenfold.
Adapted from material in the public domain.282
3-56
Medications for Opioid Use Disorder TIP 63
•
• Potential for misuse and diversion exists.
People can misuse buprenorphine via intra-
nasal or IV routes or divert it for others to
misuse. Do not give early or multiple reflls
without careful assessment and monitoring
suited to the patient’s level of stability.283,284
Discourage misuse and diversion by:
− Requiring frequent offce visits until
patients are stable.
− Testing urine for buprenorphine and norbu-
prenorphine or buprenorphine glucuronide
(both metabolites of buprenorphine).
− Using other methods to ensure adequate
adherence to the medication as pre-
scribed, such as developing and adopting
a diversion control plan (see Chapter 3E:
Medical Management Strategies).
• Adrenal insuffciency has been reported
with opioid use, most often after more than
1 month of buprenorphine maintenance.285
• Patients will develop physical dependence
on buprenorphine. Alert patients that they’ll
experience opioid withdrawal if they stop
buprenorphine.
• Buprenorphine may affect cognition and
psychomotor performance and can have
sedating effects in some people (particularly
those who’ve lost tolerance after a period of
abstinence from opioids). Concurrent use of
illicit drugs, other prescribed medications, or
medical or psychiatric comorbidity can affect
cognition and psychomotor performance.
Urge patients to exercise caution in using
heavy machinery and driving until they’re sure
that their abilities are not compromised.286
• Allergic reactions have occurred in patients
treated with buprenorphine, including rash,
urticaria, angioedema, and anaphylaxis.
• Buprenorphine can cause precipitated
opioid withdrawal. It has weaker opioid
agonist effects and stronger receptor affnity
than full agonists (e.g., heroin, methadone).
It can displace full agonists from receptors,
precipitating opioid withdrawal.287 Factors
affecting this possibility include:
− Current level of opioid physical depen-
dence. The higher the level of physical
dependence, the higher the likelihood of
precipitating withdrawal.288 Ensuring that
patients are in opioid withdrawal when
initiating buprenorphine decreases this risk.
− Time since the last mu-opioid receptor full
agonist dose. The longer the time since
the last dose, the lower the likelihood of
precipitated withdrawal.289
− Dose of buprenorphine administered. The
smaller the dose of buprenorphine, the less
likely it is to precipitate withdrawal.290,291
• Neonatal abstinence syndrome (NAS) may
occur in newborns of pregnant women
who take buprenorphine. Women receiving
opioid agonist therapy while pregnant should
talk with their healthcare provider about NAS
and how to reduce it. Not all babies born to
women treated with opioid agonists require
treatment for NAS. Research has shown that
the dose of opioid agonist medication is not
reliably related to the severity of NAS.292,293,294
Thus, each woman should receive the dose of
medication that best manages her illness.
REDUCING NAS SEVERITY
Offer the following advice to pregnant women
receiving treatment with an opioid agonist:
• Avoid smoking during pregnancy.
• Avoid benzodiazepines.
• Meet with the neonatologist and/or pediatrician
to learn how the hospital assesses and treats
NAS and what they suggest you can do as a
parent to help soothe a baby with NAS.
• Request rooming-in with the child.
• Talk with the healthcare professional providing
obstetric care about breastfeeding, as this may
help make NAS less severe.
• In the frst week after birth, keeping lights low,
speaking softly, avoiding too much stimulation,
and providing frequent skin-to-skin contact can
help prevent or limit symptoms of NAS.
3-57
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Drug Interactions
Buprenorphine has fewer documented
clinically signifcant drug interactions than
methadone.295 Monitoring is still needed for
patients who are starting or stopping medi-
cations that are CYP450 3A4 enzyme inhibitors
or inducers or that compete with buprenorphine
for this enzyme. A previously therapeutic and
stable dose of either buprenorphine or the
coadministered medication may be altered when
one of these medications is started or stopped.
In the case of buprenorphine, oversedation or
withdrawal symptoms may result. In the case of
altered levels of other pharmacotherapies, the
patient may experience a lack of therapeutic
beneft or toxic side effects of that drug. Special
attention should be paid to patients using or
starting depot formulations of buprenorphine.
Prior to initiating a depot formulation, talk with
the patient about waiting until any time-limited
therapy with a potential inhibitor, inducer, or
substrate of CYP450 3A4 is complete, and
ensure that adherence to any such medications
needed chronically is good. Make sure the
patient fully understands the possible risk of
fuctuations in buprenorphine serum levels
resulting in sedation or withdrawal symptoms
and if compliance with an inhibitor, inducer, or
substrate of CYP450 3A4 is erratic. If an inhibitor,
inducer, or substrate of CYP450 3A4 is to be
started or stopped for a patient stable on a
depot formulation of buprenorphine, the patient
should be monitored closely for oversedation
or signs of withdrawal. Remember, signs and
symptoms may not appear until the new med-
ication approaches a therapeutic blood level.
Signs of withdrawal may be relieved, if necessary,
with the short-term use of additional low doses
of transmucosal buprenorphine. Patients who
experience sedation may need to take safety
precautions with some activities. In severe cases,
removal of the depot formulation, if possible,
may need to be considered. Exhibit 3D.3
EXHIBIT 3D.3. Partial List of Medications Metabolized by Cytochrome
P450 3A4
Drugs that may DECREASE buprenorphine serum levels
Drug Mechanism
Anticonvulsants
Phenobarbital, phenytoin,
primidone, carbamazepine Induces cytochrome P450 3A4
Antibiotics
Rifampin Induces cytochrome P450 3A4
Immune Suppressants
Dexamethasone Induces cytochrome P450 3A4
Drugs that may INCREASE buprenorphine serum levels
Drug Mechanism
Antibiotics
Clarithromycin Inhibits cytochrome P450 3A4
Clindamycin, dapsone,
erythromycin Competes with buprenorphine for cytochrome P450 3A4 enzyme
Antidepressants
Fluoxetine, fuvoxamine,
nefazodone Inhibits cytochrome P450 3A4
Continued on next page
3-58
Medications for Opioid Use Disorder TIP 63
EXHIBIT 3D.3. Partial List of Medications Metabolized by Cytochrome
P450 3A4 (continued)
DRUGS THAT MAY INCREASE BUPRENORPHINE SERUM LEVELS
DRUG MECHANISM
Antifungals
Fluconazole, itraconazole,
miconazole
Inhibits cytochrome P450 3A4
Ketoconazole Inhibits and competes with buprenorphine for cytochrome P450 3A4
Antihypertensives
Nicardipine, verapamil Inhibits cytochrome P450 3A4
Amlodipine, diltiazem, felodipine,
nifedipine, nimodipine
Competes with buprenorphine for cytochrome P450 3A4 enzyme
Antiarrhythmics
Amiodarone Inhibits cytochrome P450 3A4
Disopyramide, quinidine Competes with buprenorphine for cytochrome P450 3A4 enzyme
Hormones
Estrogen, oral contraceptives,
progestins
Competes with buprenorphine for cytochrome P450 3A4 enzyme
Sedative/Hypnotics
Alprazolam, clonazepam,
diazepam, midazolam
Competes with buprenorphine for cytochrome P450 3A4 enzyme
Immune Suppressants
Cyclosporine, zafrlukast Inhibits cytochrome P450 3A4
Statins
Atorvastatin, lovastatin,
simvastatin
Competes with buprenorphine for cytochrome P450 3A4 enzyme
Gastric Agents
Aprepitant, cimetidine Inhibits cytochrome P450 3A4
Analgesics
Fentanyl Competes with buprenorphine for cytochrome P450 3A4 enzyme
Antihistamines
Loratadine Competes with buprenorphine for cytochrome P450 3A4 enzyme
Chemotherapeutics
Doxorubicin, etoposide,
ifosfamide, paclitaxel, vinblastine
Competes with buprenorphine for cytochrome P450 3A4 enzyme
Blood Thinners
Warfarin Competes with buprenorphine for cytochrome P450 3A4 enzyme
Note: Consult a point-of-service medical reference application for the most up-to-date drug–drug interactions
before making medication management decisions.
Adapted from material in the public domain.296
3-59
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
partially lists these medications, including
some anticonvulsants, and antibiotics, and
Exhibit 3D.4 lists HIV medications. More informa-
tion on drug–drug interactions is available online
(www.drugs.com
/drug-interactions/buprenorphine-index.html
?flter=3&generic_only=).
Monitor responses to buprenorphine in
patients taking nonnucleoside reverse tran-
scriptase inhibitors. Changes in buprenorphine
concentrations can be clinically signifcant.297
Combination antiretroviral therapy (atazana-
vir/ritonavir) increases buprenorphine and
norbuprenorphine serum concentrations.298
Case reports have demonstrated signs of
buprenorphine excess (sedation). Decreasing
buprenorphine can improve this symptom.299
Other research has demonstrated no need to
adjust the buprenorphine dose among patients
taking atazanavir.300
For tuberculosis treatment, rifampin but not
rifabutin may decrease buprenorphine concen-
trations. Rifampin produced opioid withdrawal
in 50 percent of research volunteers with opioid
dependence.301
FDA warns of increased serotonin syndrome
risk with prescription opioids, including bu-
prenorphine. Serotonin syndrome can include:
• Changes in mental status.
• Fever.
• Tremor.
• Sweating.
• Dilated pupils.
EXHIBIT 3D.4. Potential Interactions Between Buprenorphine and HIV
Medications
MEDICATION TYPE POTENTIAL INTERACTION
Atazanavir Protease inhibitor Increased buprenorphine concentrations. May cause
cognitive impairment302,303 or oversedation.304,305
Slower titration or dose reduction of buprenorphine
may be warranted.306,307
Darunavir-ritonavir Protease inhibitor Some pharmacokinetic (PK) effect; dose adjustments
unlikely to be needed, but clinical monitoring is
recommended.308
Delavirdine Nonnucleoside reverse
transcriptase inhibitor
Increased buprenorphine concentrations, but no
clinically signifcant effect. Dose adjustments unlikely
to be needed. However, use with caution, as long-
term effects (more than 7 days) are unknown.309,310
Efavirenz Nonnucleoside reverse
transcriptase inhibitor
Some PK effect; dose adjustments unlikely to be
needed.311
Elvitegravir (with
cobicistat)
Integrase inhibitor Some PK effect; no dose adjustments needed.312
Nevirapine Nonnucleoside reverse
transcriptase inhibitor
Some PK effect; no dose adjustments needed.313
Ritonavir Protease inhibitor Some PK effect; no dose adjustments needed.314
Tipranavir Protease inhibitor Some PK effect; no dose adjustments needed.315
Adapted from material in the public domain.316
3-60
Medications for Opioid Use Disorder TIP 63
−
−
Serotonin syndrome can occur with simultaneous
opioid and antidepressant treatment. There are
only a few case reports of serotonin syndrome
with buprenorphine,317 but be aware of this
possibility given the frequent treatment of mood
disorders in patients with OUD.
Side Efects
Buprenorphine’s side effects may be less
intense than those of full agonists. Otherwise,
they resemble those of other mu-opioid
agonists. Possible side effects include the
following (buprenorphine FDA labels list all
potential side effects https://dailymed.nlm.nih
.gov/dailymed/drugInfo.cfm?setid=8a5edcf9
-828c-4f97-b671-268ab13a8ecd):
• Oral hypoesthesia (oral numbness)
• Constipation
• Glossodynia (tongue pain)
• Oral mucosal erythema
• Vomiting
• Intoxication
• Disturbance in attention
• Palpitations
• Insomnia
• Opioid withdrawal syndrome
• Excessive sweating
• Blurred vision
Serious implant-related adverse events are
uncommon but possible according to the FDA
label (www.accessdata.fda.gov/drugsatfda_docs
/label/2016/204442Orig1s000lbl.pdf). Still, more
than 10 percent of patients experience implant
site pain, itching, or swelling. Migration beyond
the local insertion site is rare but possible, as is
nerve damage. Buprenorphine may be extruded
from implants for potential misuse. Insert
implants only in stable patients, for whom FDA
has approved this formulation.
Implants may extrude and potentially come
out (e.g., from incomplete insertion or infection).
Tell patients to call the implanting physician if
an implant looks like it is extruding or comes
out. If the implant comes out, patients should
safely store and dispose of it (following local
and federal regulations) to protect others from
unintended exposure.
Serious injection site adverse events for the
extended-release formulation are uncommon
but possible. The most common injection site
adverse reactions were pain (7.2 percent),
pruritus (6.6 percent), and erythema (4.7 percent)
in phase three trials. Two cases of surgical
removal of the monthly depot were reported
in premarketing clinical studies. Surgical
excision under local anesthesia within 14 days
of injection is possible. It is recommended that,
before treatment, baseline liver function tests
be assessed with monthly monitoring during
treatment, particularly with the 300 mg dose.
There are limited data regarding use of the
extended-release injection formulation in
pregnant women with OUD. In animal repro-
ductive studies with Sublocade’s excipient,
N-Methyl-2-pyrrolidone, there were reported
fetal adverse reactions. Women should be
advised that the use of Sublocade during
pregnancy should be considered only if the
benefts outweigh the risks (see FDA package
insert for full details www.accessdata.fda.gov
/drugsatfda_docs/label/2017/209819s000lbl.pdf).
Assessment
No evidence clearly predicts which patients
are best matched to buprenorphine versus
other OUD medications. Thorough assess-
ment helps determine whether buprenorphine
treatment is appropriate for a patient. (Part 2 of
this TIP covers screening and assessment in more
detail.) Before prescribing buprenorphine:
• Check the state prescription drug monitoring
program database.
• Assess the patient’s history.
Conduct a medical, psychiatric, substance
use, and substance use treatment history.
Assess recent opioid use, including
frequency, quantity, type, route, and last
day of use.
3-61
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
− Establish OUD diagnosis.
− Assess for other substance use disorders
(SUDs), including those involving alcohol,
benzodiazepines, or stimulants.
• Conduct a focused physical examination,
refer for a physical exam, or get a record of a
recent one.
− Assess for signs and symptoms of intoxi-
cation. Do not give a frst dose to a patient
who is sedated or intoxicated. Assess and
treat him or her appropriately.
− Assess for evidence of opioid with-
drawal and physiological dependence.
The Clinical Opioid Withdrawal Scale
(COWS) or the Clinical Institute Narcotic
Assessment (CINA) Scale for Withdrawal
Symptoms can be used to assess
withdrawal signs (see “Resource Alert:
Opioid Withdrawal Scales”). The patient
should exhibit signs of opioid withdrawal
before taking the frst dose of buprenor-
phine to avoid precipitated withdrawal.
For example, the Risk Evaluation and
Mitigation Strategy (REMS) for buprenor-
phine indicates that a COWS score of 12 or
higher is typically adequate for a frst dose.
Confrming opioid withdrawal suggests
that the patient is physically dependent
on opioids and can begin induction with a
typical 2 mg/0.5 mg or 4 mg/1 mg bu-
prenorphine/naloxone dose.
• Obtain laboratory tests.
− Conduct drug and alcohol tests. Use
reliable urine tests for opioids (including
morphine, methadone, buprenorphine,
and oxycodone), benzodiazepines,
cocaine, and other drugs commonly used
in the area. Use a breathalyzer to estimate
the patient’s blood alcohol content. Do not
provide buprenorphine until the alcohol
reading is considerably below the legal
level of alcohol intoxication.
− Conduct a pregnancy test. Transmucosal
buprenorphine or methadone maintenance
treatment is recommended for OUD
in pregnancy.318 There are limited data
regarding use in pregnant women with
OUD with the buprenorphine implants and
with the extended-release injection for-
mulation. If buprenorphine is used during
pregnancy, it should generally be trans-
mucosal monoproduct.319 Refer pregnant
patients to prenatal care.
− Assess liver function. If possible, obtain
liver function tests, but do not wait for
results before starting transmucosal
buprenorphine treatment. A patient
with chronic hepatitis can receive OUD
treatment with buprenorphine. Discuss
risks and benefts if the patient’s liver
enzymes are at or above fve times the
normal level and monitor liver function
during treatment. Patients with transam-
inase levels less than fve times normal
levels, including patients with hepatitis
C virus, appear to tolerate buprenor-
phine well.320,321 Exhibit 3D.2 gives more
information about hepatic impairment
and buprenorphine. Liver function tests
should be obtained and reviewed before
initiating buprenorphine implants or
extended-release buprenorphine because
these formulations are long acting.
RESOURCE ALERT
Opioid Withdrawal Scales
The COWS and other opioid withdrawal
scales can be downloaded from Annex 10
of WHO’s Guidelines for the Psychosocially
Assisted Pharmacological Treatment of Opioid
Dependence from the National Center for
Biotechnology Information website (www.ncbi
.nlm.nih.gov/books/NBK143183).
The CINA Scale for Withdrawal Symptoms is
also available online (www.ncpoep.org/wp
-content/uploads/2015/02/Appendix_7_Clinical
_Institute_Narcotic_Assessment_CINA_Scale
_for_Withdrawal_Symptoms.pdf).
3-62
Medications for Opioid Use Disorder TIP 63
− Conduct hepatitis and HIV tests.
Hepatitis B and C are common among
patients entering buprenorphine
treatment. HIV infection is also prevalent.
Everyone ages 15 to 65 should be tested
at least once for HIV. Persons at higher risk,
such as people who use drugs by injection,
should be tested annually.322 Anyone who
is injecting or has ever injected drugs, even
once, no matter how long ago, should be
tested for hepatitis C, regardless of their
intention to seek treatment for SUD.323 The
Centers for Disease Control and Prevention
recommends hepatitis B vaccination for
individuals seeking treatment for SUDs.324
Patient Selection
No evidence clearly predicts which patients
are best treated with buprenorphine versus
other OUD medications. Inform all patients
with OUD about treatment with transmucosal
buprenorphine and where it’s available. (See
“Treatment Planning or Referral” in Part 2 of this
TIP for more on shared decision making.)
Patients who responded well to buprenorphine
in the past should be considered for this
treatment.
Prior use of diverted buprenorphine doesn’t
rule out OUD treatment with buprenorphine.
Diverted buprenorphine is often associated with
an inability to access treatment,325 and it’s often
used to self-treat opioid withdrawal rather than
to “get high.”326,327
Unsuccessful treatment experiences with
buprenorphine in the past do not necessarily
indicate that buprenorphine will be ineffective
again. Motivation and circumstances change
over time. Also, treatment varies by provider,
clinic, and setting, as it does for other medical
illnesses. Records from previous providers can
contextualize the extent of past treatment.
Pregnant women should be considered for
transmucosal buprenorphine treatment.
Do not taper patients to 8 mg daily
solely to switch them to implants.
Stable patients are the best candidates for
buprenorphine implants. Implants are indicated
for patients who have already achieved illicit
opioid abstinence and clinical stability while
taking transmucosal buprenorphine for at least
90 days. Their current dose should be 8 mg/
day or less.328 There is no absolute defnition of
clinical stability, but per the implant package
insert, patients may be stable if they are:329
• Abstaining currently from illicit opioids.
• Having little or no craving for illicit opioids.
• Living in a stable environment.
• Participating in a structured job or activity.
• Engaging in a positive social support system.
• Lacking recent hospitalizations, emergency
department visits, or crisis interventions for
substance use or mental illness.
• Adhering to clinic appointments and other
aspects of treatment and recovery plans.
Informed Consent
Inform all patients of:
• Their OUD diagnosis and the nature of the
disorder.
• Risks and benefts of all available medications
for OUD.
• Risks and benefts of nonmedication
treatments.
Educate patients about basic buprenorphine
pharmacology and induction expectations
(Exhibit 3D.5). They should understand the need
to be in opioid withdrawal that’s visible to the
Use language and written materials
appropriate to each patient’s
comprehension level to ensure that
he or she understands the options
and can make informed decisions.
3-63
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
EXHIBIT 3D.5. Key Points
of Patient Education for
Buprenorphine
Before starting OUD treatment with
buprenorphine, patients should:
prescriber (or, for home induction, that meets
predefned self-assessment criteria) to avoid
precipitated withdrawal.
Initiating Buprenorphine
Treatment
It can be helpful to use a buprenorphine
treatment agreement for patients treated in
offce-based settings (see Chapter 3D Appendix
for a sample treatment agreement).
Induction can occur in the offce or at home.
Most clinical trials were conducted with offce-
based induction, and extant guidance recom-
mends this approach.330 However, offce-based
induction can be a barrier to treatment initia-
tion. Home induction is increasingly common.331
Ofce-Based Induction
Providers can perform offce-based induction
by ordering and storing induction doses in the
offce or by prescribing medication and instruct-
ing patients to bring it to the offce on the day
of induction. Offce-based induction allows
providers to:
• Ensure that patients know how to take
medication without swallowing or spitting it
out if they have too much saliva or experience
unpleasant tastes. Tell them to wait to eat or
drink until the medication is totally dissolved.
• Enhance the therapeutic relationship.
• Verify the presence of opioid withdrawal
and absence of precipitated opioid
withdrawal.
• Ensure the lack of sedation 1 to 2 hours
after the frst dose in patients taking
sedatives.
• Use time between doses for patient self-
assessment. See the Chapter 3D Appendix
for sample goal-setting forms that help
patients identify treatment goals and triggers
for use.
Home Induction
Home induction can be safe and effective.332
Retention rates are similar to offce inductions,333
but no comparison data from large randomized
• Tell providers the prescribed and over-the-
counter medications they take to allow drug
interaction assessment.
• Understand the goal of the first week of
treatment: To improve withdrawal symptoms
without oversedation.
• Tell providers if they feel sedated or euphoric
within 1 to 4 hours after their dose.
• Be given the appropriate buprenorphine
medication guide.
• Know possible side effects, including:
- Headache.
- Dizziness.
- Nausea.
- Vomiting.
- Sweating.
- Constipation.
- Sexual dysfunction.
• Agree to store medication securely and out of
the reach of others.
• Alert providers if they discontinue
medications, start new ones, or change their
medication dose.
• Understand that discontinuing
buprenorphine increases risk of overdose
death upon return to illicit opioid use.
• Know that use of alcohol or benzodiazepines
with buprenorphine increases the risk of
overdose and death.
• Understand the importance of informing
providers if they become pregnant.
• Tell providers if they are having a procedure
that may require pain medication.
• Be aware of resources through which to
obtain further education for:
- Themselves: Decisions in Recovery:
Treatment for Opioid Use Disorder (https://
store.samhsa.gov/product/SMA16-4993)
- Their families and friends: Medication-
Assisted Treatment for Opioid Addiction:
Facts for Families and Friends (https://portal.
ct.gov/-/media/DMHAS/Opioid-Resources/
MATInfoFamilyFriendspdf.pdf)
3-64
Medications for Opioid Use Disorder TIP 63
controlled studies exist. The American Society of
Addiction Medicine National Practice Guideline
recommends home induction only if the patient
or prescriber has experience with using buprenor-
phine.334,335 Clinical experience indicates that
patients suitable for home induction:
• Can describe, understand, and rate
withdrawal.
• Can understand induction dosing instructions.
• Can and will contact their provider about
problems.
Educate patients about how to assess their
withdrawal, when to start the frst dose, how
to take the medication properly, and how to
manage withdrawal on induction day. Instruct
patients to take their frst dose when they expe-
rience opioid withdrawal at least 12 hours after
last use of heroin or a short-acting prescription
opioid. Effectively switching from methadone to
buprenorphine can be challenging. This should
generally be started with offce-based induction.
Consult with a medical expert knowledgeable
about methadone in these situations until experi-
ence is gained. Withdrawal can include:
• Goose bumps.
• Nausea.
• Abdominal cramps.
• Running nose.
• Tearing.
• Yawning.
Be available for phone consultation during the
induction period and for an in-offce evalua-
tion should the need arise. See patients in the
Advise patients to abstain from
tobacco before dosing. Many patients
with OUD use tobacco products.
Nicotine causes vasoconstriction,
decreasing the surface area of blood
vessels that absorb buprenorphine.
offce within approximately 7 days of the start of
home induction. (See the Chapter 3D Appendix
for a sample buprenorphine/naloxone home
dosage schedule.)
Induction
Patients who are currently physically
dependent on opioids
Patients should begin buprenorphine when
they are exhibiting clear signs of opioid
withdrawal. Induction typically starts with a
2 mg to 4 mg dose of buprenorphine or a 2
mg/0.5 mg to 4 mg/1 mg dose of buprenor-
phine/naloxone.336 Depending on the formula-
tion used and whether a given patient has a dry
mouth, the dose can take between 3 and 10
minutes to dissolve fully. After approximately
2 hours, an additional 2 mg to 4 mg dose of
buprenorphine/naloxone can be given if there
is continued withdrawal and lack of sedation.
Always individualize dosing. The FDA label
recommends a maximum buprenorphine/
naloxone dose of 8 mg on Day 1 and 16 mg on
Day 2.337 When dosing outside of FDA recom-
mendations, document the clinical rationale,
including risks and benefts. Remember that
some patients stabilize on lower doses.
If patients experience sedation upon frst
dose, stop and reevaluate the following:
• Did they recently take other sedating
medications (e.g., benzodiazepines)?
• Have they recently been in a controlled envi-
ronment, such as a hospital, jail, or residential
drug treatment facility?
• Was the history of recency and amount of
opioid use inaccurate?
• Was the heroin used of poor quality?
• Was their use mostly of low-potency opioids
(e.g., codeine)?
Consider whether a dose decrease, change
in treatment plan, or both are necessary. If
induction is still indicated, adjust the dose
3-65
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
more slowly as needed to minimize sedation.
The dose can be adjusted on subsequent days to
address continued withdrawal or uncontrollable
craving if the patient is not sedated.
Patients with a history of OUD who are not
currently physically dependent on opioids
Buprenorphine induction can be appropriate
for certain patients with a history of opioid
addiction at high risk for return to use of opioids
but not currently dependent on them. This
includes patients who’ve been incarcerated
or in other controlled environments.338 Before
starting treatment, discuss risks and benefts of
buprenorphine and other medications (including
extended-release naltrexone [XR-NXT]).
Buprenorphine doses should begin at lower-
than-usual levels (e.g., 1 mg). They should be
increased more slowly than in tolerant patients
to avoid oversedation and possible overdose.
Take particular care with patients who are being
treated with other central nervous system
depressant medications.339 At the beginning
of treatment, directly administer doses in an
OTP or in the offce. This will allow patients to
be observed for sedation after dosing and will
reduce the risk that patients take more
medication than prescribed.
In one study, research participants not currently
physically dependent on opioids but with a
history of OUD were started on 1 mg buprenor-
phine with weekly 1 mg dose increases to 4 mg,
followed by 2 mg weekly increases to 8 mg.
Most patients tolerated this dose induction, and
the mean daily dose exceeded 8 mg per day
by the ffth week, when the planned dose was
6 mg.340 As with all opioid agonist treatment,
dosing should be individualized and based on
careful patient assessment during treatment.
Patients who are currently taking
methadone
Some patients who take methadone may wish to
switch to buprenorphine treatment for a variety
of reasons. This often requires methadone
dose reduction before switching medications,
which may increase the risk of return to opioid
use. Exercise caution with this approach and
thoroughly discuss the risks and benefts with
the patients before embarking on the change
in medication. Experienced prescribers should
conduct this procedure in the offce, not via
home induction. The lower the methadone dose
and the longer it’s been since the last dose, the
easier the transition.
Before initiating buprenorphine, carefully
taper methadone to lower the risk of return
to illicit opioid use during transition. Patients
who take methadone for OUD should taper to
30 mg to 40 mg methadone per day and remain
on that dose for at least 1 week before starting
buprenorphine.341 With patients’ permission,
OTPs can confrm the time and amount of
patients’ last methadone dose.
Do not start buprenorphine until the patient
manifests signs of opioid withdrawal. At least
24 hours should pass between the last dose of
methadone and the frst dose of buprenorphine.
Waiting 36 hours or more reduces risk of pre-
cipitated withdrawal. Lower doses of buprenor-
phine/naloxone are less likely to precipitate
methadone withdrawal.342 For example, once
opioid withdrawal is verifed, an initial dose of
2 mg/0.5 mg can be given. If patients continue
to have unrelieved opioid withdrawal after the
frst 2 mg dose, administer another 2 mg/0.5 mg
dose approximately every 2 hours as needed
(holding for sedation). Induction should be
conducted slowly; consider palliating unrelieved
withdrawal with nonopioid therapies for the frst
few days of transition to buprenorphine. Be alert
to any increase in withdrawal symptoms, as this
may suggest precipitated withdrawal.
Dose Stabilization
Stabilization occurs when there is evidence of:
• Markedly reduced or eliminated illicit opioid
use.
• Reduced craving.
3-66
Medications for Opioid Use Disorder TIP 63
• Suppression of opioid withdrawal. Buprenorphine treatment should substantially
• Minimal side effects.
• Patient-reported blunted or blocked euphoria
during illicit opioid use.
Remind patients to take their dose once daily
rather than splitting it. Document reduced illicit
drug use via patient self-report and urine drug
testing. Consecutive negative urine test results
suggest a positive prognosis.
Continue monitoring dose effectiveness
during early stabilization. Dose adjust-
ments may still be necessary (Exhibit 3D.6).
reduce opioid cravings. See Chapter 3E: Medical
Management Strategies for detailed information
on the management of patients taking buprenor-
phine in offce-based treatment settings.
Once patients have stabilized, continue to
screen and evaluate for mental disorders and
psychosocial problems that may need to be
addressed (e.g., having a spouse or cohabitant
who is using illicit opioids). Support patients’
engagement in prosocial activities and progress
toward treatment goals and recovery as they
decrease use of illicit substances.
EXHIBIT 3D.6. Adjusting the Buprenorphine Dose
When to increase the dose:
• Are patients taking medication correctly and as scheduled?
- If they take at least 16 mg per day, mu-opioid receptors are approximately 80 to 95 percent occupied.343
- If there are adherence problems, assess causes and intervene to promote adherence and proper
administration (e.g., offer supervised dosing at the clinic, by a network support, at a pharmacy).
- If patients are taking doses correctly, a dose increase may be indicated, if certain conditions exist.
• Are patients taking other medications that may interfere with buprenorphine metabolism?
• If patients are taking doses properly, increase the dose if they still have opioid withdrawal (document
with a clinical tool like COWS), opioid craving, or “good” effects (e.g., feeling “high”) from using illicit
opioids.
- Craving can be a conditioned response. It may not decrease with dose increases if patients spend
time with people who use opioids in their presence.
- Dose increases typically occur in 2 mg to 4 mg increments.
- It will take about 5 to 7 days to reach steady-state plasma concentrations after a dose increase.
- Offer psychosocial referrals to help decrease and manage cravings.
• Determine whether nonpharmacological problems are contributing to the need for increase.
- For example, do patients show signs and symptoms of untreated major depressive or generalized
anxiety disorders? Are they living in a chaotic household? Do they have childcare problems or
fnancial diffculties? Are they experiencing trauma or trauma-related mental disorders?
- Address or refer to counseling to address these problems.
When to decrease the dose:
• Decrease the dose when there is evidence of dose toxicity (i.e., sedation or, rarely, clearly linked
clinically relevant increases in liver function tests).
• Hold the dose when there is acute alcohol or benzodiazepine intoxication.
3-67
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Offer referrals for adjunctive counseling and
recovery support services as needed. It may
not be possible to eliminate opioid craving
completely, regardless of the dose. Counseling
can help patients reduce and manage craving.
A more important measure of dose adequacy
than craving is whether patients report that
the feeling of euphoria associated with self-
administered illicit opioids is blunted or blocked.
Patients who were not interested in adjunc-
tive addiction or mental health counseling
during induction may become receptive to it
when they are feeling more stable.
Be cautious when increasing doses above 24
mg/6 mg per day. Nearly all patients stabilize
on daily doses of 4 mg/1 mg to 24 mg/6 mg.
Very limited data show additional benefts of
doses higher than the FDA label’s recommended
maximum of 24 mg/6 mg.344 Carefully document
clinical justifcation for higher doses and always
have a diversion control plan in place. Doses
above 24 mg/6 mg a day may unintentionally
heighten diversion risk. Patients not responding
to high doses of buprenorphine at the upper
limit approved by FDA should be considered for
methadone treatment.
Risk Evaluation and Mitigation Strategy
Practitioners should become familiar with the
FDA-approved REMS for buprenorphine. It
provides useful information and checklists for
providers. REMS can be found online for:
• Buprenorphine monoproduct and
buprenorphine/naloxone
(www.accessdata.fda.gov/scripts/cder
/rems/index.cfm?event=IndvRemsDetails
.page&REMS=352)
• Transmucosal buprenorphine
(www.accessdata.fda.gov/scripts/cder
/rems/index.cfm?event=RemsDetails
.page&REMS=9)
• Buprenorphine implants
(www.accessdata.fda.gov/scripts/cder
/rems/index.cfm?event=IndvRemsDetails
.page&REMS=356)
• Buprenorphine extended-release injection
(www.accessdata.fda.gov/scripts/cder
/rems/index.cfm?event=indvremsdetails
.page&rems=376)
See also “Buprenorphine Induction and
Maintenance Appropriate Use Checklists” in
Chapter 3D Appendix.
Transmucosal Buprenorphine Dosing
Summary
Induction and stabilization
The goal is to reduce or eliminate opioid with-
drawal and craving without causing sedation:
• Induction and stabilization strategies can
vary based on patient variables and use of
short- versus long-acting opioids. For more
discussion on induction models, see the
Providers’ Clinical Support System’s Models
of Buprenorphine Induction (http://pcssmat
.org/wp-content/uploads/2015/01/Models
-of-Buprenorphine-Induction.pdf).
• The combination buprenorphine/naloxone
product is safe to use for induction for most
patients.
• The buprenorphine monoproduct (without
naloxone) has been recommended for the
treatment of pregnant women345 because of
the danger to the fetus of precipitated opioid
withdrawal if the combination product were to
be injected. Although there are some publica-
tions with small sample sizes that indicate that
the combination product appears to be safe in
pregnancy,346,347 the safety data are insuffcient
at this time to recommend its use.348 This is
an area of some uncertainty. An expert panel
on the treatment of OUD in pregnancy was
unable to agree whether pregnant women
should be treated with the monoproduct or
combination product.349
• Prescribers should observe the patient taking
the medication to ensure proper use, espe-
cially if the patient is new to buprenorphine
treatment. It can be helpful to do this peri-
odically after induction, especially when the
prescribed dose is not providing the expected
beneft.
3-68
Medications for Opioid Use Disorder TIP 63
• Before the frst dose, the patient should be
in opioid withdrawal (to avoid precipitated
withdrawal).
• The frst dose is typically 4 mg/1 mg (2 mg if
withdrawal is from methadone).
• Repeat dose as needed for continuing with-
drawal every 2 hours up to typically 8 mg on
the frst day.
At the start of the next day, patients typically
take the frst day’s total dose all at once:
• If necessary, an additional 2 mg to 4 mg can
be given every 2 hours up to approximately
a 16 mg total daily dose to treat continuing
opioid withdrawal and craving on Day 2 or 3,
barring sedation.
• The initial stabilization dose can often be
achieved within the frst several days of
treatment.
Maintenance
Typical maintenance doses range from 4 mg/1
mg to 24 mg/6 mg per day. An effective main-
tenance dose is the lowest dose that can:
• Eliminate withdrawal.
• Reduce or eliminate opioid craving.
• Reduce or stop illicit opioid use’s desirable
effects.
• Be well tolerated (e.g., not produce sedation).
Duration of treatment
• Treatment should last for as long as patients
beneft from treatment.
• Longer treatment length is associated with
positive treatment outcomes.
Initiation of Buprenorphine Implants
Prescribers and implanters of buprenorphine
implants require special certifcation to make
this formulation available to their patients. In
addition, implanters must get special training in
the Probuphine REMS program to obtain certi-
fcation to implant and remove this formulation.
After completing training, providers can order
implants through a central pharmacy for delivery,
along with an implant insertion kit that contains
all necessary implant procedure materials
except a local anesthetic. If the prescriber is not
performing the procedure, the prescriber should
ensure that the implanter has completed the
required training. For more information, see the
Probuphine REMS program webpage (https://
probuphinerems.com/).
The prescriber and implanter/remover must
record the number of implanted/removed
rods and their serial numbers and location, the
date of the implant, and who performed the
procedure. The implanter should document
implant and inspection procedures, as with any
other standard procedure.
Instruct patients to take the last transmu-
cosal dose of buprenorphine 12 to 24 hours
before insertion. Remind them to shower and
thoroughly wash the nondominant arm, which is
preferred for insertion.
Implant procedure
Subdermal insertion of the four rods takes less
than 30 minutes. Local anesthetic (lidocaine) is
typically used. The implant procedure includes
the following steps:
• Provide education about what to expect
during the procedure.
• Obtain appropriate consent form(s).
• Provide a local anesthetic (e.g., lidocaine).
• Using sterile procedures, make a single
incision in the inner upper arm between the
biceps and triceps muscles, about 8 cm to 10
cm from the medial epicondyle.
• Using a cannula and an obturator, insert rods
serially, pivoting the cannula slightly after
each rod insertion in the subdermal space so
that the rods lie next to one another, nearly
parallel in a fanlike pattern.
• After implantation, apply butterfy strips and a
pressure bandage.
• Review wound care with the patient, and
provide a copy of the instructions.
• Advise the patient not to drive or engage
in heavy physical activity for approximately
24 hours.
3-69
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
• Do not give the patient a prescription for
transmucosal buprenorphine at this time.
Wound care
The patient should return within 1 week of the
implant procedure for a wound care check.
Check for signs of infection, trouble healing, or
implant extrusion. The rods are subdermal, so
they should remain palpable. Document that all
four rods were palpated.
Stabilization
Maintain contact with patients after implant
placement. Even among highly stable patients,
return to illicit opioid use can occur. Explain the
risk of unintentional overdose if patients return
to illicit opioid or alcohol or benzodiazepine
use while implants are in place. It is important
to monitor the patient between implant
placements.
Schedule offce visits no less than once a
month for continued assessment of main-
tenance of stability, manual palpation of the
four implanted rods, and ongoing psychosocial
support and counseling per the FDA label (www
.accessdata.fda.gov/drugsatfda_docs/label/2016
/204442Orig1s000lbl.pdf). If the patient returns
to illicit opioid use, consider whether adequate
psychosocial treatment has been given.
Consider transmucosal medication supplemen-
tation if a patient with implants destabilizes
and reports inadequate opioid blockade. In
one study,350 17.9 percent of participants with
buprenorphine implants needed supplemental
sublingual buprenorphine/naloxone. Most
required small doses, such as 2 mg/0.5 mg per
day. Consider more frequent assessment and
higher intensity of treatment for patients who
continue using illicit opioids or other substances.
Removal
After 6 months, have a certifed implanter
remove them. Implantation of a second set
of rods in the opposite arm can then occur.
There is no experience with inserting additional
implants into other sites or second insertion into
a previously used arm. After one insertion in
each arm, most patients should transition to a
transmucosal buprenorphine-containing product
for continued treatment. Patients should follow
the same directions to prepare for implant
removal as they did for insertion. The removal
procedure may require stitches. Patients should
visit the clinic for removal of stitches and wound
assessment within 1 week of removal. Store and
dispose of rods safely in accordance with local
and federal regulations.
Initiation of Buprenorphine Extended-
Release Injection
Healthcare settings and pharmacies need
special certifcation to order and dispense
extended-release injectable buprenorphine to
ensure long-acting preparations are dispensed
directly to healthcare providers for administra-
tion and by healthcare providers to patients (see
www.accessdata.fda.gov/scripts/cder/rems/index
.cfm?event=indvremsdetails.page&rems=376 for
more details).
Before initiating extended-release buprenor-
phine treatment, patients with moderate-
to-severe OUD should be stabilized on trans-
mucosal buprenorphine (8 mg to 24 mg daily)
for at least 7 days. Do not use in opioid-naïve
patients. Obtain liver function and pregnancy
tests. Extended-release buprenorphine is not
recommended for patients with severe hepatic
impairment and may not be appropriate for
patients with moderate hepatic impairment
because of the long-acting nature of this formu-
lation. There are insuffcient data on its use in
pregnancy to recommend initiating this formula-
tion during pregnancy.
Inform patients that:
• The medication is only available in a restricted
program (the Sublocade REMS Program) via
specifc pharmacies and healthcare providers,
as intravenous self-injection by patients can
cause death.
• After abdominal injection, a lump may be
present at the injection site for a few weeks. It
3-70
Medications for Opioid Use Disorder TIP 63
will get gradually smaller. Patients should not
rub or massage it or let belts or waistbands
rub against it.
• Patients should tell their healthcare providers
that they are being treated with this
medication.
• Using alcohol, benzodiazepines, sleeping pills,
antidepressants, or some other medications
with extended-release buprenorphine can
lead to drowsiness or overdose.
• The most common side effects are constipa-
tion, headache, nausea, vomiting, increased
liver enzymes, tiredness, and injection site
itching or pain.
• Patients should inform their provider if they
become pregnant during treatment with this
formulation. They should have a risk/beneft
discussion about continuing with this for-
mulation given the limited safety data on its
impact on the developing fetus. They should
be informed that their newborn can have
symptoms of opioid withdrawal at birth.
Storage
Follow package insert directions for medication
storage under refrigeration. Keep at room
temperature for at least 15 minutes before
injection (discard if left at room temperature for
more than 7 days).
Administration
Rotate the abdominal subcutaneous injection
site with each injection, following the instructions
in the package insert. Record the location of
each injection in the medical record. Each of the
frst two monthly doses (with at least 26 days
between doses) should be 300 mg. Subsequent
monthly doses should be 100 mg. Some patients
may beneft from increasing the maintenance
dose to 300 mg monthly if they have tolerated
the 100 mg dose but continue to use illicit
opioids.
Medical management
Monitor patient progress and response to
treatment during regular offce visits and
with periodic urine drug testing. Examine
the injection site for reactions, infections, or
evidence of attempts to remove the depot
medication. If the medication is discontinued,
the patient should continue to be seen and
evaluated for several months for sustained
progress in treatment and for signs and
symptoms of opioid withdrawal, which should be
treated as clinically appropriate.
Duration of Buprenorphine
Treatment
There is no known duration of therapy with
buprenorphine (or methadone or XR-NTX) after
which patients can stop medication and be
certain not to return to illicit opioid use. Those
who stay in treatment often abstain longer from
illicit opioid use and show increasing clinical
stability. Long-term treatment outcomes up to 8
years after buprenorphine treatment entry show
lower illicit opioid use among those with more
time on medication.351
Patients should take buprenorphine as long
as they beneft from it and wish to continue.
Successful Buprenorphine Treatment
The goal of buprenorphine treatment is full
remission from OUD. Maintaining illicit opioid
abstinence is ideal, but imperfect abstinence
does not preclude treatment benefts. Patients
should do better in treatment than before
treatment. If not, seek alternatives.
Do not judge treatment progress and success
on the amount of medication a patient needs
or how long treatment is required. Rather,
gauge treatment progress and success based
Given the often-chronic nature of OUD
and the potentially fatal consequences
of unintended opioid overdose, it
is critical that you base patients’
length of time in treatment on their
individual needs.
3-71
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
on patients’ achievement of specifc goals that
were agreed on in a shared decision-making and
treatment planning process.
Consider this analogy: A patient with poorly
controlled diabetes was previously unable to
work and was admitted to the hospital several
times for diabetic ketoacidosis. When taking
insulin regularly, the patient worked part time,
had fewer hospitalizations for diabetic ketoaci-
dosis despite a nondiabetic diet, and had lower
(but still high) hemoglobin A1C. This patient’s
treatment with insulin is not a “failure” because
perfect control and function were not restored,
and the patient would not be discharged from
care against his or her will.
Dose Tapering and Buprenorphine
Discontinuation
Following short-term medically supervised
withdrawal, patients frequently restart illicit
opioid use.352 In contrast to short-term medically
supervised withdrawal, dose tapering refers to
gradually reducing the buprenorphine dose in
patients who have been stabilized on the medi-
cation for some time.
Base decisions to decrease dose or stop
buprenorphine on patients’ circumstances and
preferences. Successful dose reductions may
be more likely when patients have sustained
abstinence from opioids and other drugs,
psychosocial support, housing, effective coping
strategies, stable mental health, employment,
and involvement in mutual-help programs or
other meaningful activities.353 However, there is
no guarantee that even patients with years of ab-
stinence, full-time employment, stable housing,
and psychosocial supports can remain abstinent
after discontinuing buprenorphine.
It is up to patients to decide whether to
taper or eventually discontinue medication.
Help them make informed choices by educating
them about the process and fully including
them in decision making. Invite them to reenter
treatment if they believe they may return or have
already returned to opioid use.
Before beginning to taper the dose of med-
ication, explore these considerations with
patients:
• How have they responded to treatment
so far? Are they in full remission from OUD?
Do they have adequate mental and social
supports to remain in remission and maintain
recovery?
• Why do they want to taper? They may be
motivated by inconvenience, expense, loss
of insurance coverage, side effects, feelings
of shame, pressure from family, and lack of
recovery supports. Many of these reasons are
not predictive of a successful outcome.
• What do they expect to be different after
tapering or discontinuing buprenorphine?
• Do they understand the risks and benefts
of dose decrease and discontinuation of
buprenorphine?
• What strategies do they have for engaging
family members and recovery supports to
reduce the risk of return to illicit substance
use?
• Do they grasp the risk of overdose associ-
ated with a return to illicit opioid use?
• Do they have a safety plan? To reduce
overdose risk after a return to use, plans
should include:
− A prescription for naloxone or a naloxone kit.
− Instructions on recognizing and responding
to an overdose.
− Information on naloxone use for family
members and others in the patient’s
recovery support network.
− See the SAMHSA Opioid Overdose
Prevention Toolkit (https://store.samhsa.
gov/product/Opioid-Overdose-Prevention-
Toolkit/SMA18-4742) for more guidance.
3-72
Medications for Opioid Use Disorder TIP 63
− If patients return to opioid use, it may be
appropriate for them to restart buprenor-
phine or switch to methadone or XR-NTX
treatment. These options should be
discussed with them.
• Have they thought about how they will feel
if they attempt to taper off of medication
but cannot do so? Convey to patients that
the inability to taper is not a failure and that
they should not be afraid or embarrassed to
discuss stopping the taper.
Document the discussion, patient education,
and decision in the medical record.
There is no ideal tapering protocol. Providers
and patients should understand this before
beginning a taper. Whether buprenorphine is
ultimately discontinued, patients need additional
psychosocial and recovery support during
this time. Generally, taper occurs over several
months to permit patients to acclimate to the
lower dose and to reduce potential discomfort
from opioid withdrawal and craving.
For patients who wish to discontinue
buprenorphine, national and international
guidelines recommend gradual dose reductions
and advice to patients that they can stop the
taper at any time.354,355,356
Consider increased monitoring and proactive
discussions about how to address and manage
cravings and withdrawal symptoms. Taper
protocols vary in duration and may include use of
ancillary medication, such as clonidine, if needed
(Exhibit 3A.2).357
Continue to monitor patients who successfully
taper off buprenorphine completely. Establish
a post-taper monitoring and support plan (see
Chapter 3E for more information on medical
management strategies). Continue to assess and
monitor patients’ progress and how they cope
with stress and triggers to use. Discuss the role of
XR-NTX in preventing return to opioid use after
completing treatment with an opioid agonist (see
Chapter 3C for more information on naltrexone).
3-73
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3D Appendix
Buprenorphine Induction and Maintenance Appropriate Use Checklists
Continued on next page
3-74
Medications for Opioid Use Disorder TIP 63
Available online (www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2017-01-23_Appropriate_Use_Checklist.pdf).
Reprinted from material in the public domain.358
3-75
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Sample Goal Sheet and Coping Strategies Form
Patient’s Name: _______________________________________________________________ Date: _________________________
3-MONTH 1
GOALS
2
3
6-MONTH 1
GOALS
2
3
1-YEAR 1
GOALS
2
3
List of Triggers to Using Drugs
People To Stay Away From
Places To Stay Away From
Ways To Cope or Manage Stress Without Using Drugs
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
3-76
Medications for Opioid Use Disorder TIP 63
Sample Goal-Setting Form
Patient’s Name: ________________________________________________________________ Date: _________________________
GOAL CATEGORY
CURRENT
SITUATION SCORE
10 = major problems
and 0 = no problems
What would need
to change to decrease
this score?
PRIORITY SCORE
10 = highest priority (“I really
want to work on this”) and
1 = lowest priority (“I really do
not want to work on this”)
Opioid use
Other illicit drug use: ______________
Alcohol use
Tobacco use
Physical health
Mental health
Legal/court issues
Finances
Job/employment
Hobbies
Family relations
Partner relations
Supportive drug-free network
Education
Keeping medication safe
(e.g., not giving it away, selling it,
having it stolen)
Other
Other
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
3-77
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Buprenorphine/Naloxone Home Dosage Schedule: Films or Tablets
Name: ________________________________________________________________ Date: ___________________________
Procedure for taking buprenorphine:
• Let the medication dissolve under your tongue for at least 10 minutes. Do not suck on it.*
• Do not eat, drink, or smoke cigarettes for 30 minutes after you take your medication.
• Wait 2 hours between each dose.
The maximum dose is 16 mg/4 mg. If you reach this dose, you cannot increase further without calling the offce frst.
The offce phone number is ____________________________________ [insert phone number].
Day 1 Induction Day (In Offce): You have taken a total dose of _______ mg.
Day 2 in the Morning: Take the total dose you took on Day 1 = _______ mg.
• If you experience withdrawal 2 hours later, you may take one 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: __________________________________.
• If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: __________________________________.
Your total dose on Day 2 cannot exceed _______ mg. Record your total dose on Day 2: ______ mg.
Day 3 in the Morning: Take the total dose you took on Day 2 = _______ mg.
• If you experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: ___________________________________.
• If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: _____________________________________.
Your total dose on Day 3 cannot exceed _______ mg. Record your total dose on Day 3: ______ mg.
Day 4 in the Morning: Take the total dose you took on Day 3 = _______ mg.
• If you experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: ___________________________________.
• If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet.
• Record your withdrawal symptoms: _____________________________________.
Your total dose on Day 4 cannot exceed _______ mg. Record your total dose on Day 4: ______ mg.
Day 5 to next visit: In the morning, take the total dose you took on Day 4 = _______ mg.
General Rules
• The maximum dose is 16 mg/4 mg. If you reach this dose, you cannot increase further without calling the offce frst.
The offce phone number is _______________________________ [insert phone number].
• Please call if you have any questions. There are no “stupid” questions.
• Call us if you feel sleepy after your dose.
• Please bring this record to your next visit.
• It’s okay to take Tylenol (acetaminophen) or Motrin (ibuprofen) for aches/pains.
BRING THIS WITH YOU TO YOUR NEXT APPOINTMENT, scheduled for ______________________ [insert date and time].
Notes:
*If prescribing the buccal flm, ensure the patient understands that the buccal flm is placed on the inner cheek (buccal
mucosa) rather than sublingually (under the tongue).
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
3-78
Medications for Opioid Use Disorder TIP 63
Buprenorphine Treatment Agreement
This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care.
Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances
of their individual patients and practice arrangements. The information provided in this form is provided “as is”
with no guarantee as to its accuracy or completeness.
TREATMENT AGREEMENT
I agree to accept the following treatment contract for buprenorphine offce-based opioid addiction treatment:
1. The risks and benefts of buprenorphine treatment have been explained to me.
2. The risks and benefts of other treatment for opioid use disorder (including methadone, naltrexone, and
nonmedication treatments) have been explained to me.
3. I will keep my medication in a safe, secure place away from children (for example, in a lockbox). My plan is to
store it [describe where and how _____________________________________________________________________].
4. I will take the medication exactly as my healthcare provider prescribes. If I want to change my medication dose,
I will speak with my healthcare provider frst. Taking more medication than my healthcare provider prescribes
or taking it more than once daily as my healthcare provider prescribes is medication misuse and may result in
supervised dosing at the clinic. Taking the medication by snorting or by injection is also medication misuse and
may result in supervised dosing at the clinic, referral to a higher level of care, or change in medication based on
my healthcare provider’s evaluation.
5. I will be on time to my appointments and respectful to the offce staff and other patients.
6. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical
problems.
7. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider without
consulting my buprenorphine prescriber.
8. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance
so that my pain will be adequately treated.
9. If I miss an appointment or lose my medication, I understand that I will not get more medication until my next
offce visit. I may also have to start having supervised buprenorphine dosing.
10. If I come to the offce intoxicated, I understand that my healthcare provider will not see me, and I will not receive
more medication until the next offce visit. I may also have to start having supervised buprenorphine dosing.
11. I understand that it’s illegal to give away or sell my medication; this is diversion. If I do this, my treatment will no
longer include unsupervised buprenorphine dosing and may require referral to a higher level of care, supervised
dosing at the clinic, and/or a change in medication based on my healthcare provider’s evaluation.
12. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in
treatment termination from the clinic.
13. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will
count as a positive drug test.
14. I understand that I will be called at random times to bring my medication container into the offce for a pill or flm
count. Missing medication doses could result in supervised dosing or referral to a higher level of care at this clinic
or potentially at another treatment provider based on my individual needs.
15. I understand that initially I will have weekly offce visits until I am stable. I will get a prescription for 7 days of
medication at each visit.
16. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug
tests in a row. I will then get a prescription for 14 days of medication at each visit.
17. I will go back to weekly visits if I have a positive drug test. I can go back to visits every 2 weeks when I have two
negative drug tests in a row again.
18. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me.
19. I understand that people have died by mixing buprenorphine with alcohol and other drugs like benzodiazepines
(drugs like Valium, Klonopin, and Xanax).
Continued on next page
3-79
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
20. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to comply
with my healthcare provider’s recommendations for additional counseling and/or for help with other problems.
21. I understand that there is no fxed time for being on buprenorphine and that the goal of treatment is for me to
stop using all illicit drugs and become successful in all aspects of my life.
22. I understand that I may experience opioid withdrawal symptoms when I stop taking buprenorphine.
23. I have been educated about the other two FDA-approved medications used for opioid dependence treatment,
methadone and naltrexone.
24. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting
buprenorphine treatment and been informed about methods for preventing pregnancy.
Other specifc items unique to my treatment include:
Patient’s Name (print): _____________________________________________________
Patient’s Signature: ________________________________________________________ Date: ____________________
This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is
updated periodically; the most current version of the agreement is available online (www.asam.org/docs
/default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn
=bd4675c2_0).
Adapted with permission.359
3-80
Medications for Opioid Use Disorder TIP 63
Patient Urine Drug Screen and Medication Count Monitoring Form
Patient’s Name: ______________________________________________________ Date To Be Called:______________________
Called for:
□ Urine Drug Screen
□ Medication Count at □Offce or □Pharmacy FOR: _____________________________________________________________
□ Buprenorphine/Naloxone
□ Other (list drug: ___________________________, ___________________________, ___________________________)
Documentation of Phone Call to Patient
Patient was called at _____________________________ (insert phone #) on ____________________ (date) at
_____:_____ (time) and informed of monitoring required (described above) within the next _______ hours.
Check One:
□ I spoke with patient
□ Message left on answering machine/voicemail
□ Message left with ________________________________________________
□ Other __________________________________________________________
Signature of Staff Member Making Phone Call: _______________________________________________________
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
3-81
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
________________________________________________
Pharmacy Tablet/Film Count Form
(Note: Before sending this form, discuss with the pharmacist frst to explain goals and procedures and to ensure
agreement and understanding.)
Date: ___________________
To: Pharmacists @ ________________________________________ Pharmacy
From: Healthcare Provider: ____________________________________________
Clinic Address: _________________________________________________
Phone Number: ________________________________________________
My patient, __________________________________, is starting offce-based buprenorphine treatment for opioid
dependence.
As part of monitoring this treatment, we ask the patient to do buprenorphine tablet/flm counts at random times (we
call the patient when it’s time for a pill/flm count).
The above-named patient lives much closer to your pharmacy than to our treatment clinic. It would be a big help to
me and this patient if you would be able to perform periodic tablet/flm counts on his/her buprenorphine and then fax
this form to us.
On the days we call the patient for a random tablet/flm count, the patient would come to your pharmacy with his or
her pill bottle. When we call the patient to go for a random tablet/flm count, we will fax this form to you. We would
appreciate if you could record the tablet/flm count results on this form and fax it back to us the same day. This would
be a real help to me in monitoring my patient’s treatment and also a great service to the patient.
Thank you very much for your help with this! Sincerely,
Signature
Buprenorphine/Naloxone formulation: _________________________________________
Dose per tablet/flm: _______________
Total # of tablets/flms remaining in bottle: ______________ Fill date on bottle: ___________________
Total # of tablets/flms dispensed on fll date: ____________ Tablet/flm count correct? □Yes □No
Please fax this back to: _____________________________________
Thank You!
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
This page intentionally left blank.
3-83
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3E: Medical Management Strategies
for Patients Taking OUD Medications in
Ofce-Based Settings
Chapter 3E examines key issues in medical management of patients who are prescribed
buprenorphine or naltrexone in offce-based opioid treatment (OBOT) settings. It covers
regulatory and administrative concerns specifc to buprenorphine and naltrexone that
affect medical management of patients in offce settings.
Management of patients taking medications
for opioid use disorder (OUD) varies by
setting. Whereas OBOT stabilizes patients on
buprenorphine or naltrexone, providers focus
on medication management and treatment of
other substance use, medical comorbidities,
and psychosocial needs. Treatment of comorbid
conditions should be offered onsite or via referral
and should be verifed as having been received.
Exhibit 3E.1 addresses use of terminology in this
chapter.
EXHIBIT 3E.1. Key Terms
In addition to the key terms defned in Exhibit
3.1 of this Treatment Improvement Protocol
(TIP), these terms appear in Chapter 3E:
Psychosocial support: Ancillary services
to enhance a patient’s overall functioning
and well-being, including recovery support
services, case management, housing,
employment, and educational services.
Psychosocial treatment: Interventions
that seek to enhance patient’s social and
mental functioning, including addiction
counseling, contingency management, and
mental health services.
Patient Selection
To assess patients’ chances of success with
standard offce-based treatment, consider:
• Concurrent substance use disorder (SUD)
involving alcohol or benzodiazepines.
Benzodiazepine (illicit and prescription) and
alcohol use are common in patients with OUD.
This use presents clinical challenges, including
increased risk of respiratory depression
and unintentional overdose or death. Some
patients may have taken appropriately pre-
scribed benzodiazepines for years with limited
or no evidence of misuse. For such patients,
tapering benzodiazepines may be contrain-
dicated and unrealistic. Others may require
treatment for a benzodiazepine use disorder.
(See Exhibit 3B.1 for strategies for assessing
and managing patients in OUD treatment who
have concurrent benzodiazepine use disorder.)
• Although concomitant use of buprenorphine
with benzodiazepines increases the risk of
an adverse reaction, including overdose
death, opioid agonist treatment should not
be denied to patients solely because they
take benzodiazepines,360 because untreated
OUD can pose a greater risk of morbidity and
mortality. The Food and Drug Administration
(FDA) advises that careful medication man-
agement by healthcare professionals can
reduce risk (see www.fda.gov/Drugs/Drug
Safety/ucm575307.htm for more information).
3-84
Medications for Opioid Use Disorder TIP 63
Approaches to addressing concurrent benzo-
diazepine use include:
− Get patients’ permission to contact their
benzodiazepine prescribers to confrm
their histories. Speaking with close family
members or friends (with patients’ permis-
sion) can also help in evaluating evidence
of alcohol or benzodiazepine misuse (e.g.,
intoxication, accidents, withdrawal seizures).
− Make sure patients understand that
combining buprenorphine with alcohol,
benzodiazepines, or other central nervous
system depressants risks potential re-
spiratory depression and unintentional
overdose death.361 Overdose death with
buprenorphine is most often associated
with intravenous benzodiazepine and
heavy alcohol use.
− For patients misusing benzodiazepines
(e.g., taking in high doses, bingeing, using
intravenously), the TIP expert panel recom-
mends referral to higher intensity addiction
treatment with medically supervised ben-
zodiazepine withdrawal if available (e.g.,
intensive outpatient programs, residential
treatment). Do not rule out concurrent use
of buprenorphine or extended-release in-
jectable naltrexone (XR-NTX) for treatment
of OUD in more structured settings for
these patients.
− For patients who are physically dependent
on illicit benzodiazepines but do not inject
or binge, a gradual outpatient medically
supervised withdrawal can be attempted
using long-acting benzodiazepines, under
certain conditions that promote safety and
reduce risk. These conditions may include:
• Requiring frequent offce visits with ob-
servation of patients taking medication.
• Having signifcant others monitor
patients and report back to the offce.
• Offering a short-duration prescription
supply.
• Monitoring prescription drug monitoring
program (PDMP) reports more frequently.
• Conducting frequent urine tests.
• Using written treatment agreements
outlining conditions for dual buprenor-
phine and benzodiazepine prescriptions.
− Review patient progress regularly; adjust
treatment plans as needed. Document
treatment decisions, as research showing
the effectiveness and safety of these
approaches is lacking.362
• Signifcant comorbid mental illness or
suicidal or homicidal ideation. Patients
who are actively suicidal, homicidal, severely
depressed, or psychotic or who are having
other signifcant psychiatric problems may
need assessment and treatment by a mental
health professional who can treat both
the psychiatric comorbidity and the OUD.
Depending on the severity, they may need
higher levels of mental health services in
a crisis center, emergency department, or
inpatient setting. An addiction psychiatrist can
treat such patients upon discharge.
• Signifcant medical comorbidity, including
infections. Severe abscesses, endocarditis, or
osteomyelitis from injecting drugs may require
hospitalization. If hospitalization is necessary,
buprenorphine can be initiated.363 Initiation of
HIV and hepatitis C virus treatments do not
contraindicate buprenorphine treatment.364
Patient Management and
Treatment Monitoring
Base management of OUD on a comprehen-
sive assessment that is updated throughout
treatment (see Part 2 of this TIP for more
information on conducting assessments). Tailor
the management approach to patients’ needs
and goals. Components of the management
approach include:
• The length and frequency of offce visits.
• The length of time between prescriptions or
XR-NTX injections.
• The frequency of drug testing.
• Ancillary psychosocial and medical treatments
and referrals.
3-85
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Course of Treatment
The typical course of OUD treatment is
varied. There is often not a direct pathway
from heavy illicit opioid use to no illicit opioid
use.365 Some patients have only occasional
returns to use and do not require reinduction
on buprenorphine or naltrexone. Other patients
may return to use in the context of medication
nonadherence, requiring reinduction and
restabilization on buprenorphine or medically
supervised withdrawal from opioids and an ap-
propriate period of abstinence before restarting
naltrexone. Some patients may have sustained
abstinence and choose to remain on their
maintenance buprenorphine or naltrexone dose.
However, others may try to taper their buprenor-
phine dose, discontinue naltrexone, consider a
change in medication (e.g., from buprenorphine
to naltrexone or naltrexone to buprenorphine),
or attempt maintenance of remission of OUD
without any medication.
Because OUD is often a chronic and relapsing
illness, patients may have different types and
durations of treatment over their lifetimes.
Some may have periods of successful outpa-
tient treatment at different times with all three
available FDA-approved medications for OUD.
Others may experience forced medication
discontinuation (e.g., insurance lapse, time
in controlled environments that disallow or
discriminate against OUD medication, cases in
family and drug courts, parole and probation).
A relative few may remain in remission after
successfully discontinuing medication voluntarily.
Different treatment journeys occur in different
treatment settings (e.g., intensive outpatient,
residential programs) and with different phar-
macotherapies and ancillary psychosocial and
recovery support services.
To the extent possible, coordinate primary
care, behavioral health, and wraparound
services needed and desired by the patients
to address their medical, social, and recovery
needs. Individuals with co-occurring physical,
mental, and substance use disorders may beneft
from collaborative care.366
RESOURCE ALERT
Substance Abuse and Mental Health Services Administration (SAMHSA)
Treatment Guidance for Individuals With Co-Occurring Disorders
TIP 42, Substance Use Disorder Treatment for People With Co-Occurring Disorders, provides
treatment strategies for SUD treatment for individuals with mental disorders (https://store.samhsa.gov/
product/TIP-42-Substance-Abuse-Treatment-for-Persons-With-Co-Occurring-Disorders/SMA13-3992).
General Principles for the Use of Pharmacological Agents To Treat Individuals With Co-Occurring
Mental and Substance Use Disorders offers assistance for the planning, delivery, and evaluation of
medication for individuals with co-occurring mental and substance use disorders (https://store.samhsa.
gov/product/general-principles-use-pharmacological-agents-treat-individuals-co-occurring-mental).
Pharmacologic Guidelines for Treating Individuals With Post-Traumatic Stress Disorder and Co-
Occurring Opioid Use Disorders is tailored to the provision of medication for OUD to individuals
also diagnosed with posttraumatic stress disorder (https://store.samhsa.gov/product/pharmacologic-
guidelines-treating-individuals-post-traumatic-stress-disorder-co-occurring).
3-86
Medications for Opioid Use Disorder TIP 63
Role of the Treatment Plan and
Treatment Agreement in Medical
Management
The initial treatment plan should include:
• Treatment goals.
• Conditions for changing or stopping
treatment (the Chapter 3E Appendix has a
sample goal-setting form).
• Therapeutic contingencies for nonadher-
ence and failure to meet initial goals, such
as:
− Increase in the intensity or scope of
services at the offce or through referral.
− More intensive psychosocial treatment,
including inpatient treatment or transfer
to an opioid treatment program (OTP)
for observed buprenorphine dosing if the
offce-based practice is unable to provide
such services.
− Reassessment to ensure psychiatric and
other comorbid addictions are adequately
addressed via consultation with mental
health, addiction treatment, or pain
management providers as available and
indicated.
Some patients may need a more structured
environment when there is continued opioid
use or comorbid use of substances other than
opioids or when mental disorders are impeding
their progress toward remission and recovery. In
these cases, medication for OUD should not be
interrupted.
Treatment agreements can help clarify expec-
tations for patients and healthcare profession-
als (see the Chapter 3C Appendix and Chapter
3D Appendix for sample treatment agreement
forms for XR-NTX and buprenorphine, respec-
tively). Review and amend treatment plans and
treatment agreements periodically as patients
progress (or destabilize) and new goals emerge.
This will help healthcare professionals across
settings deliver coordinated, effective care.
Updating treatment plans and agreements helps
If a patient does not discontinue all
illicit drugs for extended periods, it
doesn’t mean treatment has failed
and should not result in automatic
discharge. It means the treatment plan
may require modifcation to meet the
patient’s needs.
patients recognize their progress and supports
their motivation to remain engaged. Involving
patients’ support networks makes patients
accountable to a group of caring people rather
than to a single healthcare professional.
Engage patients’ family members and other
recovery supports (with patients’ written
consent) by sharing their treatment goals and
agreements. Identify specifc ways they can
support patients’ goals.367
Medical Management Strategies
Medical management includes:
• Providing brief supportive counseling.
• Referring to ancillary psychosocial services.
• Referring to psychiatric and medical care if
not directly provided by the healthcare pro-
fessional prescribing or administering OUD
medication.
• Adjusting the frequency of offce visits.
• Conducting drug tests.
• Monitoring patient adherence to medication
with occasional observed dosing, random
medication inventorying, or both.
• Addressing patient concerns about side effects.
The TIP expert panel recommends
medication management and brief
supportive counseling at each
visit. Refer for adjunctive addiction
counseling and other psychosocial
supports as clinically indicated.
3-87
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
• Discussing any concerns with the patient or
their support network.
• Prescribing medication for co-occurring
alcohol use disorder (e.g., disulfram,
acamprosate).
Strategies for optimizing medical management
and brief supportive counseling involve:
• Helping the patient manage stressors and
identify triggers for a return to illicit opioid
use.
• Providing empathic listening and nonjudg-
mental discussion of triggers that precede
use or increased craving and how to manage
them.
• Providing ongoing assessment to mark
progress. Revise treatment goals via shared
decision making to incorporate new insights.
(See “Treatment Planning or Referral” in Part
2 of this TIP for more on shared decision
making.)
• Providing medical care for comorbid health
conditions.
• Referring patients as needed to:
− Adjunctive psychiatric treatment.
− Addiction counseling.
− Case management.
− Community-based recovery support
groups.
• Inviting supportive family members and
friends to medical visits to discuss strategies
to support patients.
• Engaging and educating family members
and friends who are reluctant to accept
medication’s role in treatment.
• Advocating for patients as needed if
their treatment becomes threatened by
their employer, housing provider, insurance
company, the courts, or criminal justice
agencies. These threats, refusal of service, or
frank coercion may constitute potential viola-
tions of the Americans with Disabilities Act or
other discrimination or parity violations.
Referral to counseling and other
psychosocial supports
Prescribers of buprenorphine must be able
to refer patients for appropriate adjunctive
counseling and ancillary services as needed
according to federal law.368 (However, patients
can still receive buprenorphine treatment even
if they do not use such services.) There’s no such
referral requirement for naltrexone treatment,
but patients should receive medical manage-
ment and be referred as needed for adjunctive
addiction, mental health, or recovery services.
To achieve clinical stability and abstinence
from illicit drug use, many patients need
psychosocial counseling and support services
beyond what their buprenorphine prescriber’s
practice offers. For example, patients with
mental disorders (e.g., depression, posttrau-
matic stress disorder)369 should be assessed
and treated with appropriate medications (as
indicated) and adjunctive mental health services.
Some patients are reluctant to engage in
addiction counseling or recovery support
groups until they stabilize on medication. Once
stabilized, they may see benefts to participating
in these supports. Recommend additional
addiction, mental health, and social services as
appropriate if patients:
• Do not achieve full remission.
• Continue to misuse nonopioid substances.
• Do not reach their treatment goals with
medication management alone.
Behavioral treatment with contingency manage-
ment (e.g., rewards for illicit drug abstinence)
is highly effective and is offered in some
specialty treatment programs. It can motivate
the patient to reduce illicit drug use, including
opioids and stimulants, and increase medication
adherence.370
Alcoholics Anonymous, Narcotics Anonymous,
Self-Management and Recovery Training, and
other peer recovery support groups can be
3-88
Medications for Opioid Use Disorder TIP 63
helpful to patients, especially if they fnd
groups with accepting attitudes toward OUD
medication and people who take it. (See Part
5 of this TIP for resources on recovery support
groups.) Some peer recovery support groups
consider patients taking methadone and bu-
prenorphine for OUD treatment as not being
abstinent from opioids. Check with local groups
before referring a patient. Groups not accepting
of OUD medications are not appropriate for
patients taking them. Patients are most likely
to beneft from peer support programs if they
actively participate in offered recovery activities.371
Monitor recovery activities to ensure that
patients are accessing appropriate supports
and are benefting from them (Exhibit 3E.2).
Patients may need many other psychosocial
services. Case managers can help patients
obtain:
• Housing support.
• Medicaid or other health insurance.
• Income support.
• Food assistance services.
• Vocational and educational services.
• Mental health and family therapy.
Refer to psychosocial services as appropriate.
Get patient consent to share information and
make provider introductions, just as referrals to
other medical specialists would occur. Strategies
include:
• Referring per program availability, afford-
ability, and patients’ needs, preferences,
and treatment responses. Ensure referrals to
programs that accept and support patients
receiving OUD medication.
• If possible, personally introducing patients to
the new behavioral health service providers or
peer recovery support specialists if changing
settings, to encourage a successful transition.
• Developing and maintaining a list of referral
resources, including:
− Drug and alcohol counselors.
− Inpatient, residential, and outpatient
addiction counseling programs.
− OTPs.
− Inpatient/outpatient behavioral health
programs.
− Primary care and mental health providers.
− Community-based services.
− Recovery support groups.
EXHIBIT 3E.2. Monitoring Recovery Activities
At medical management visits, do not simply ask about attendance at recovery support meetings—
explore the level of participation and engagement in those activities. Some activities include:
• Finding and working closely with a sponsor.
• “Working” the 12 Steps at 12-Step meetings and with a sponsor.
• Doing service at meetings (e.g., setting up chairs, making coffee, going on a “commitment” to speak at
a meeting in a jail or an inpatient drug and alcohol program).
• Having and frequently attending a regular “home” group.372
Remember this statement from recovery experts A. Thomas McLellan and William White:
Recovery status is best defned by factors other than medication status.
Neither medication-assisted treatment of opioid addiction nor the cessation
of such treatment by itself constitutes recovery. Recovery status instead
hinges on broader achievements in health and social functioning—with or
without medication support.”373
3-89
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
• Using active referral procedures (e.g., linking
patients directly via phone to a specifc
program staff member) instead of passive
ones (e.g., giving a patient a name and a
phone number to call).
• Avoiding leaving patients to fnd their own
referrals.
• Monitoring patients’ follow-through via phone
contact or at the next offce visit.
Frequency of medical management visits
The TIP expert panel recommends that
patients be seen approximately once a week
until they demonstrate signifcant reduc-
tions in or abstinence from illicit substance
use.374 This is also a time to ensure medication
adherence. Nonadherence to naltrexone or
buprenorphine prevents optimal treatment
outcomes. In scheduling patient visits, be
sensitive to treatment barriers such as:
• Work and childcare obligations.
• Cost of care and lack of insurance coverage.
• Driving time.
• Lack of public transportation to visits, which
may be particularly challenging for patients in
rural areas.
Goals of weekly visits include:
• Assessing patients’ clinical needs and
challenges.
• Assessing medication effectiveness and side
effects.
• Assessing functional status (e.g., home, work,
school).
• Assessing and monitoring stress coping
strategies and potential triggers for return to
substance use.
• Assessing adherence to the recommended
frequency of attendance for XR-NTX injections
or the prescribed buprenorphine dosing
regimen and responsible handling of the
medication (e.g., safely storing out of reach
of children, taking as prescribed, not sharing
or losing it).
• Monitoring use of alcohol and illicit drugs
and ensuring adequate therapeutic dosing
(e.g., opioid blockade if there is ongoing illicit
opioid use and adherence to medication).
• Following up on any referrals made, such
as adjunctive counseling, recovery support
groups, or other psychosocial services (the
Chapter 3E Appendix has a sample medical
management visit form).
Once patients adhere to therapeutic doses
of OUD medication, decrease illicit drug and
alcohol use, and increase negative opioid
toxicological samples, consider less frequent
visits. Monthly visits (or less for carefully selected
patients who have been stable on buprenorphine
for extended periods with adequate support)
are reasonable for patients taking naltrexone
or buprenorphine who show progress toward
treatment objectives. Indications that a patient is
ready to come less than weekly include:
• Several weeks of illicit opioid abstinence
based on self-report and negative drug tests.
• Adherence to appointments and treatment
plan.
• No ongoing drug use that may risk patient
safety (e.g., alcohol or benzodiazepine misuse).
• Absence of signifcant medication side effects.
• Stable mental health and medical conditions.
• Responsible handling of medication (e.g., safe
storage, no requests for early reflls).
• Absence of unexpected controlled medication
prescriptions from other providers in the
PDMP.
As visits become less frequent, consider
random urine drug testing, medication counts
(buprenorphine tablets or flms), and involve-
ment of network supports if available.
Buprenorphine implants are indicated only for
stable patients already taking transmucosal
buprenorphine with positive treatment
response. Extended-release buprenorphine
is indicated for patients treated with transmu-
cosal buprenorphine for at least 1 week. It’s
3-90
Medications for Opioid Use Disorder TIP 63
Visit frequency should not depend
only on dosing schedule for long-
acting OUD medications. Also consider
patients’ treatment needs, preferences,
and responses. To ensure continued
engagement, consider adding to the
treatment agreement the expected
visit frequency and frequency of
other ancillary treatments tailored to
patients’ needs, goals, and preferences.
expected that patients with the implants or those
treated with extended-release buprenorphine
will receive medication management services
with visits approximately weekly at the start
and then less frequently as clinically indicated
based on patient treatment response. Likewise,
patients treated with XR-NTX should be seen
more than once per month when initiating the
medication to monitor progress and assess and
address any side effects.
Drug testing in ongoing medical management
Ongoing clinical monitoring that includes
drug testing of urine or oral fuid specimens
is part of good practice. Objective evidence of
any ongoing illicit substance use is important to
consider along with patient reports. Patients may
not wish to disclose recent drug use because
of shame, fear of punishment, or even fear of
discharge from treatment.
Explain to patients that testing will help them
meet treatment goals and is not performed to
render punishments. Results help:
• Detect medication nonadherence that could
cause harm (e.g., unintentional overdose).
• Monitor abstinence and response to medica-
tion treatment.
• Counsel and improve treatment plans.
• Detect a return to illicit opioid use or other
substance use.
The TIP expert panel recommends periodic
random testing. Drug testing frequency should
be clinically determined. It should occur at least
at the time of the initial evaluation and initiation
of medication (naltrexone, buprenorphine) and
at a frequency consistent with offce visits (e.g.,
weekly initially).
Point-of-service tests give immediate results,
allowing fndings and implications to be
discussed with patients during visits. However,
some circumstances require confrmatory labo-
ratory testing, such as when the patient contests
the results and when testing for employment or
legal monitoring. In these cases, samples may
need to be collected and sent to a Department
of Health and Human Services-certifed labora-
tory under strict chain-of-custody procedure. In
addition, norbuprenorphine may not be available
in point-of-service tests and therefore, periodi-
cally, a specimen should be sent to a laboratory
for testing. Important aspects of testing include:
• Testing technology.
• The cutoffs for positive tests.
• Any administrative requirements.
• Time windows to detect a positive result.
• Cross-reactivity, sensitivity, and specifcity.
• Test interpretation. (See Part 2 for more
information about how to interpret drug
testing results.)
• Consideration of panels based on drugs most
commonly used in the region.
Conduct point-of-service drug tests following
the manufacturer’s instructions. Use Clinical
Laboratory Improvement Amendments-waived
testing kits. A provider’s offce must enroll and
pay a modest fee for certifcation. The applica-
tion is available online (www.cms.gov/Medicare
/CMS-Forms/CMS-Forms/downloads/cms116
.pdf).
3-91
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Sample collection via oral swab is straightforward;
follow the manufacturer’s directions. If collecting
urine samples, take steps to reduce the
likelihood of tampering. In settings that treat
many patients or treat patients potentially facing
criminal justice sanctions, consider taking these
measures:
• Have patients visit the bathroom alone,
without bags or jackets, to deter use of
another person’s urine specimen.
• Set the sink to run only cold water and use a
colored toilet bowl cleaner to prevent dilution
of urine specimens.
• Use specimen cups with specifc gravity
testing, if possible, to identify diluted
samples.
• Use temperature-sensitive strips in collection
cups to identify tampered specimens.
Ongoing positive opioid tests during
treatment indicate the need to reassess
the patient and revise the treatment plan.
Repeated positives may indicate that patients:
• Are not taking some or all of their medication
or may be taking the medication incorrectly.
• Need a different medication.
• Need directly observed medication adminis-
tration in the offce or at an OTP.
• Need a buprenorphine dose increase.
• Need more counseling or a higher level of
a specialty addiction treatment program.
• Need to participate in recovery support
services.
For more information on drug testing in the
primary care setting, see Technical Assistance
Publication 32, Clinical Drug Testing in Primary
Care375 (https://store.samhsa.gov/product/
tap-32-clinical-drug-testing-primary-care/sma12-
4668) and ASAM’s Consensus Statement on
Appropriate Use of Drug Testing
in Clinical Addiction Medicine.376
Opioids and opiates in point-of-service tests
Point-of-service and laboratory screening tests
for opiates only test for opioids metabolized to
morphine (e.g., codeine, heroin). Semisynthetic
and synthetic opioids, such as methadone,
buprenorphine, and others (e.g., fentanyl,
oxycodone), are not metabolized to morphine
and do not test positive on most opiate tests.
Specifc point-of-service tests exist for these
opioids.
Some point-of-service and laboratory tests can
detect methadone, buprenorphine, and other
opioids. Patients taking buprenorphine should
have buprenorphine specifcally included in their
urine test panel to assure the prescriber that the
patient is indeed taking the medication. Some
patients may put some of their buprenorphine
in the urine to mask nonadherence. Periodically
testing for a buprenorphine metabolite (e.g.,
norbuprenorphine, buprenorphine glucuronide)
is advised.
Assessing buprenorphine adherence
Medication nonadherence and diversion can
signal inadequately treated OUD (e.g., return
to use with positive urine drug tests). Assess
such behaviors clinically and develop therapeutic
responses to them.
Remember that nonadherence, misuse, and
diversion occur with other medications as
well—those with and without abuse potential.
For instance, it’s clear that opioid analgesics
have been overprescribed for pain, misused,
and diverted; they have contributed to deaths
among individuals prescribed as well as those
not prescribed these medications. Antibiotics for
bacterial infections are also overprescribed, and
patient nonadherence (e.g., not completing the
full course), misuse (e.g., saving leftover medi-
cation for a later self-diagnosed and self-treated
infection), and diversion (e.g., giving leftover
medication to ill family members or friends) can
cause signifcant public health harm, given the
spread of drug-resistant bacteria. Medication
nonadherence has largely fueled development
of longer acting medications (e.g., depot anti-
psychotics, long-acting contraceptives, XR-NTX,
buprenorphine implants).
3-92
Medications for Opioid Use Disorder TIP 63
Strategies for addressing medication non-
adherence and diversion include carefully
assessing the patient to understand under-
lying causes of the behavior. Address these
causes and monitor adherence. For instance,
if a patient gives his or her medication to a
relative on a waiting list for treatment, getting
the relative into treatment can help that patient
become adherent. Monitor adherence by:
• Asking patients to bring their unused medica-
tion into the offce for counting.
• Increasing the frequency of offce visits.
• Increasing urine drug testing.
• Talking with family members or signifcant
others.
• Writing prescriptions for shorter duration.
• Observing medication administration at the
offce, pharmacy, or OTP.
• Checking urine for buprenorphine and its
metabolites.
• Checking the PDMP.
• Avoiding doses over 24 mg (save in rare
cases).
Chapter 3D Appendix includes a sample patient
urine drug screen and medication count form, as
well as a pharmacy tablet/flm count form.
If these steps have no positive effect, patients
may need referral to higher levels of care
at OTPs or residential addiction treatment
programs. Different formulations of medications
may need to be considered.377 If a change in
setting is required, consider patients for return
to OBOT once they stabilize.
Discontinuing medication for OUD
Patients should decide whether to taper off
or discontinue medication with the support of
their healthcare professional and, if applica-
ble, their addiction or mental health counselor,
family, and peer recovery supports (e.g., peer
support specialist, recovery coach). If patients’
goals include stopping medication, discuss the
risks and benefts of discontinuing. Work closely
with patients to develop a buprenorphine
dose taper plan, if needed, and a robust plan
to sustain recovery and reengage in treatment
before any return to substance use. Before
patients begin a buprenorphine dose taper or
discontinue XR-NTX, they should demonstrate:
• Medication adherence.
• Abstinence from illicit opioid use.
• A stable living environment.
• Social support.
• Sustained improvements in functioning at
home and at school or work.
Consider treatment with XR-NTX following
successful taper from an opioid agonist or partial
agonist (after an appropriate period of absti-
nence). Data are limited on the effectiveness of
this approach.
The TIP expert panel recommends that
providers not discharge patients from
treatment solely because of continued
illicit opioid use if the benefts of treatment
continue to outweigh the risks. If risks
outweigh benefts or alternative treatments may
offer more beneft, refer patients to alternative
treatment (e.g., OTP). Discharging patients
without attempting meaningful referral when
illicit opioid use is ongoing can worsen the
patient’s condition and may be considered
patient abandonment.
Forced tapers or abrupt discontinuation
Forcing a patient to taper off of medication
for nonmedical reasons or because of ongoing
substance misuse is generally inappropriate.
Many patients are abruptly discontinued or
tapered from OUD medication against their will
while detained or awaiting trial. A randomized
Do not require discontinuation of
medication for OUD because of
incomplete treatment response. Doing
so is not a rational therapeutic response
to the predicted course of a chronic
condition.
3-93
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
trial of continuing versus tapering off methadone
for detainees found that those who kept taking
medication in detention were signifcantly more
likely to return to treatment on release.378 It is
likely that the same holds true for forced discon-
tinuation from buprenorphine during detention.
As is sometimes the case in general medical
practice, patients who are unable to pay
their bills should not be discontinued from
treatment without attempting meaningful
referral. Attempt referrals to publicly funded
addiction treatment services (e.g., specialty
treatment programs, federally qualifed health
centers). If patients cannot continue treatment
because of inability to pay, providers can contact
the pharmaceutical company about patient
assistance programs to help defer the cost of
medications.
Forced dose tapers against the patient’s
desire may be clinically indicated when risks of
treatment outweigh benefts or, in unusual cases,
where the patient has been violent toward staff
or other patients. In these cases, attempt to
place the patient in a higher level of care and
document the attempt. In some circumstances,
forced tapering or abrupt discontinuation may
violate the Americans with Disabilities Act.
The Legal Action Center (www.lac.org) and
the National Alliance for Medication Assisted
Recovery (www.methadone.org) offer informa-
tion on how to legally manage forced tapers.
Patient follow-up
Medical management should not end when
patients taper off of medication. The TIP
expert panel recommends regular follow-up
visits (or phone checkups by clinical staff or
recovery support specialists) to help patients
manage their condition, address potential
concerns about returning to illicit opioid use, and
discuss reinitiating OUD maintenance medication
if warranted. Attendance at drug counseling
or mutual-help groups can be helpful, as can
periodic drug testing.
Administrative Considerations
Patient Limits
Individual healthcare practitioners can
prescribe buprenorphine in any medical
setting, as long as they apply for and receive
waivers of the special registration requirements
defned in the Controlled Substances Act.
Several laws and regulations contain information
about which healthcare practitioners are eligible
to apply for a waiver and how to qualify (www.
samhsa.gov/medication-assisted-treatment/
training-materials-resources/apply-for-practi-
tioner-waiver). This information is summarized
below.
Eligible physicians, nurse practitioners, physician
assistants, and other qualifying practitioners
(clinical nurse specialists, certifed registered
nurse anesthetists, and certifed nurse midwives)
can apply for a waiver.
At present, clinical nurse specialists, certifed
registered nurse anesthetists, and certifed nurse
midwives are only eligible to apply for a waiver
until October 1, 2023.
For the frst year of waiver use, all providers can
treat up to 30 patients at one time. However,
providers who satisfy additional practice and
reporting requirements, and physicians who
are board certifed in addiction psychiatry or
addiction medicine, may request to treat up to
100 patients at a time in the frst year of waiver
use. Additionally, practitioners who provide
MAT in “qualifed practice settings,” as defned
in title 42, section 8.615 of the Code of Federal
Regulations, may also request to treat up to 100
patients within the frst year.
After the frst year of waiver use, all providers
may request to increase their patient limit to
100.
3-94
Medications for Opioid Use Disorder TIP 63
Physicians who are board certifed in addiction
psychiatry or addiction medicine or who satisfy
additional practice and reporting requirements
may apply to increase their patient limit to 275
after a year at the 100-patient limit.
Diversion Control Policies for OBOT With
Buprenorphine
Controlled substance diversion refers to unau-
thorized provision of medication to someone
for whom it was not prescribed.379 Patients
may divert buprenorphine for various reasons,
such as:
• To “help” someone who needs medically su-
pervised withdrawal or awaits treatment.380,381
• To provide income for the seller.
• To enable someone else to experience the
euphoric effect of the medication.382
Address diversion of controlled substances
with patients using the following strategies:
• Clarify that continuing in offce-based
treatment depends largely on taking med-
ication as prescribed; nonadherence and
diversion are thus problematic.
• In a nonjudgmental way, discuss to whom
within their network of family, friends, and
acquaintances they might be tempted to
divert their medication and why they might
be tempted to do so.
• Instruct patients to store medication
securely (children may inadvertently ingest it
and overdose, or other people may take the
medication for their own use or to sell).383
− Discuss patients’ plans to safely store
buprenorphine. Advise patients to keep
the medication in the original packaging
and out of the reach of children.384
− Tell patients not to store their medication
in common areas (e.g., kitchen, bathroom)
where others may access it.
− Educate patients that any portion of a dose
taken by a child or pet can be deadly and
that they should call 9-1-1 immediately if
this occurs.
• Explain how diversion causes negative views
of treatment, leading to discrimination against
people with OUD. Therefore, healthcare pro-
fessionals must proactively address diversion
to help prevent it.
Possible signs that a patient is diverting bu-
prenorphine385 include:
• Frequently missed appointments.
• Requests for early reflls because medication
was reportedly lost or stolen.
• Negative buprenorphine urine screens.
• Positive buprenorphine urine screens that are
negative for buprenorphine metabolites.
• Specifc requests for the buprenorphine
monoproduct owing to naloxone allergy.
• Specifc requests for doses of buprenorphine
greater than 24 mg/6 mg.
• PDMP shows prescription flls for opioids or
other medications that are not positive on his
or her drug tests.
• Failed flm/pill callback counts.
Establish a diversion control plan to minimize
OUD medication diversion. The plan provides
measures to reduce diversion and assigns
specifc responsibility to medical and admin-
istrative staff members for carrying out these
measures.386 It should address medication
storage, dispensing and administration (if
applicable), and prescribing387 (see the Chapter
3E Appendix for a sample diversion control
policy). For providers who store buprenorphine
for administration and dispensing, plans should
indicate how they will control diversion and which
approaches they will use to ensure that patients
take their medication. Exhibit 3E.3 summarizes
key elements of a diversion control plan.
Physicians who prescribe buprenorphine to
more than 100 patients need a diversion
control plan. Document diversion incidents and
responses to incidents in the patient record.
More information about Drug Enforcement
Administration (DEA) requirements for Drug
Addiction Treatment Act of 2000 (DATA
3-95
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
2000)-waivered healthcare professionals is
available online (www.deadiversion.usdoj.gov/
pubs/docs/index.html).
Storage of Buprenorphine
Practices that store buprenorphine onsite
must have appropriate security, which includes
storing the medication in a securely locked,
substantially constructed cabinet.388 If a signif-
cant amount of stored buprenorphine is lost or
stolen, providers must notify the local DEA offce
in writing within 1 business day and complete a
Form DEA-106 (https://apps.deadiversion.usdoj
.gov/webforms/dtlLogin.jsp).
Employees convicted of a felony related to
a controlled substance or who had a DEA
registration denied, revoked, or surrendered
“for cause” are not permitted to have access
to buprenorphine.
EXHIBIT 3E.3. Key Elements of an OBOT Clinic Diversion Control Plan389
New Patients
Check the state’s PDMP before admission to
determine whether patients are receiving opioids
or benzodiazepine prescriptions from other
providers.
Ask patients to sign a release of information to
speak with the other prescribers. Patients who
are unwilling to sign a release of information are
poor candidates for outpatient treatment.
Review the clinic diversion control policy with new
patients. This should include counseling patients
to:
• Keep buprenorphine locked up and out of
children’s reach.
• Never share medication with anyone.
• Never sell medication to anyone.
• Acknowledge giving or selling medication to
others as illegal.
• Take medication only as prescribed.
• Review, understand, and agree to the practice’s
buprenorphine treatment agreement before
they start.
Prescribe buprenorphine/naloxone when possible
rather than monoproduct. Exceptions include
prescribing the monoproduct for pregnant
women with OUD.
Prescribe an adequate but not excessive dose.
Most patients respond to doses at or below
24 mg per day. Carefully evaluate requests for
higher doses and confrm, document, and assess
medication adherence continuously.
Ongoing Patients
Periodically check the state’s PDMP.
Conduct random urine tests that include a
wide spectrum of opioids—including morphine,
oxycodone, and buprenorphine—and periodically
include buprenorphine metabolites. This will help
monitor response to treatment and determine
whether patients are taking at least some of their
prescribed buprenorphine.
Use unobserved specimen collection to preserve
patient privacy and dignity:
• Do not let patients bring backpacks, jackets, or
other items into the bathroom.
• Do not let others enter bathrooms with patients.
• Temperature test the urine sample.
Use observed specimen collection (obtained by
a staff member of the same gender) or oral fuid
testing if there is reason to suspect tampering or
falsifcation.
Contact patients at random; ask them to bring in
their medication within a reasonable period (24
to 48 hours) to count the tablets/flms to ensure
that all medication is accounted for.
Provide a limited number of days of medication
per prescription without reflls (e.g., several days
or 1 week per prescription) until the patient has
demonstrated stability and lowered diversion risk.
3-96
Medications for Opioid Use Disorder TIP 63
Records for Dispensers
Offce-based practices that dispense buprenor-
phine must keep records of:390
• The number of units and doses dispensed
with the names and addresses of the patients.
• The dates the medication was dispensed.
• The names (or initials) of the staff members
who dispensed or administered the
medication.
The diversion control plan should include
approaches to ensuring that patients take the
medication and do not divert it to others.
Recordkeeping for ordering, storing, and
dispensing buprenorphine in the ofce
All prescribers and staff members must follow
federal and state laws for ordering, storing,
administering, and dispensing buprenorphine
in outpatient settings. Records of inventories of
medication received, dispensed, destroyed, and
lost or stolen must be maintained. For guidance
on how to comply with federal requirements, see:
• DEA Recordkeeping Requirements for
Buprenorphine Treatment (https://docs.
clinicaltools.com/pdf/Buppractice/V5-Bup-
How-To-Comply.pdf).
Recordkeeping for prescribing buprenorphine
Consider writing an initial prescription for
only a few days. An example of a 1-day in-offce
induction prescription is:
Buprenorphine/naloxone 2mg /0.5 mg:
Dispense #4 for in-offce induction, no
reflls, fll on __________________________
[insert date that is 1 day before the
scheduled induction to make it less
tempting for patients to use on their
own before induction]
Keep a log for possible DEA inspection that
includes:
• Patients’ names (or ID numbers).
• Dates of prescriptions.
• The names, strengths, and quantities of the
medications.
Although not required, such a log facilitates
inspection and indicates that the provider is
within the approved patient limits. Alternatively,
electronic health records can be used for this
purpose.
DEA Inspections
Under DATA 2000, DEA must ensure that
providers administering, dispensing, or prescrib-
ing buprenorphine are following recordkeeping,
security, and other requirements. To fulfll this
requirement, DEA conducts routine, unan-
nounced onsite inspections. A description
of the inspection process and how to comply
with its requirements is available online (http://
pcssnow.org/wp-content/uploads/2014/02/
FINAL-How-to-Prepare-for-a-DEA-Inspection.pdf).
Emergency Protocols and Patient
Safety Measures
Clinics that provide buprenorphine or
naltrexone do not need special emergency
protocols, crash carts, or other special
equipment. However, for patient safety, the TIP
expert panel recommends having injectable
or intranasal naloxone onsite. Clinics that ad-
minister XR-NTX or buprenorphine should have
a written policy and procedure for responding to
precipitated withdrawal and medication allergies.
Providers who give more than 100
patients buprenorphine must have on-
call services. Such services are valuable
regardless of the number of patients in
treatment.
3-97
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
On-call services and backup during absences
should be available either directly or through
contracts or cooperative agreements with other
local providers with waivers. Qualifed medical
staff can offer routine medical and psychiatric
coverage even without a buprenorphine waiver.
Recommendations for Staf
Member Training
All staff members who interact with patients
are part of the treatment environment. They
can affect patients’ treatment experiences and,
ultimately, their outcomes. Staff members who
interact with patients can include receptionists,
billing clerks, urine specimen collection clerks,
and all clinical staff members. Therefore, it is
useful to educate and train all staff members
in key areas, including:
• Organizational mission.
• The scientifc and empirical underpinnings
for the use of FDA-approved medications for
OUD, how these medications work, and the
evidence for their effectiveness.
• The similarity of medical management and
support of patients with OUD to that of
patients with other chronic illnesses.
• The importance of maintaining a nonjudgmen-
tal and welcoming attitude toward patients.
• How to hold discussions about negative
perceptions and prejudices associated with
OUD.
• Side effects of OUD medications and proce-
dures to alert staff members when patients
exhibit them.
• The effect of OUD and other substance use
and mental disorders (including posttraumatic
stress disorder) on patients’ behavior and how
staff members can respond appropriately.
• Procedures for seeking help from other staff
members to deescalate disagreements or
solve problems.
• Procedures for protecting patients’ confdenti-
ality and safety.
Treating OUD can be a challenging yet
rewarding part of a clinical practice.
Addressing key administrative issues keeps the
focus on the rewarding aspects of developing
long-term relationships with patients as they
work to overcome negative effects of OUD on
their lives and improve their health.
RESOURCE ALERT
Training and Mentorship for
Prescribers
The Providers’ Clinical Support System, with the
American Academy of Addiction Psychiatry as
the lead organization along with partners from
ASAM and other professional organizations,
delivers education, training, and mentorship
to providers who wish to treat OUD with
medications. More information about training
and professional mentorship is available online
(https://pcssnow.org/education-training/).
3-98
Medications for Opioid Use Disorder TIP 63
Chapter 3E Appendix
Sample Goal-Setting Form
Patient’s Name: ________________________________________________________________ Date: _________________________
GOAL CATEGORY
CURRENT
SITUATION SCORE
10 = major problems
and 0 = no problems
What would need
to change to decrease
this score?
PRIORITY SCORE
10 = highest priority (“I really
want to work on this”) and
1 = lowest priority (“I really do
not want to work on this”)
Opioid use
Other illicit drug use: ______________
Alcohol use
Tobacco use
Physical health
Mental health
Legal/court issues
Finances
Job/employment
Hobbies
Family relations
Partner relations
Supportive drug-free network
Education
Keeping medication safe
(e.g., not giving it away, selling it,
having it stolen)
Other
Other
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
3-99
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
Sample Medical Management Visit Form
Patient’s Name: ___________________________________________________________ ID#____________________________
Date: ____________________ Week#: _________ Dose: ________ mg □ No Show
Heroin/cocaine or other illicit drug use since last visit?
Symptoms or signs that might indicate return to use (e.g., changes in mood, physical appearance)?
Since the last visit, are there any problems with the following:
If yes, explain
Drug Use □ Yes □ No
Alcohol Use □ Yes □ No
Psychiatric □ Yes □ No
Medical □ Yes □ No
Employment □ Yes □ No
Social/Family □ Yes □ No
Legal □ Yes □ No
Any new problem to add to Treatment Plan Review? □ Yes □ No
Plan to address any new problem _________________________________________________________________________________
Participation in Narcotics Anonymous or Alcoholics Anonymous since last visit? □ Yes □ No
Length of Session: ________________ Healthcare Professional Signature: ___________________________________________
D. Fiellin, December 3, 2016 (personal communication). Adapted with permission.
3-100
Medications for Opioid Use Disorder TIP 63
Sample Buprenorphine Diversion Control Policy
XYZ Medical Practice
Offce-Based Opioid Use Disorder Policy and Procedure Manual
Policy Title: Diversion Control for Patients Prescribed Transmucosal (Sublingual) Buprenorphine
Effective Date: ______________________ (Month, Day, Year)
This Diversion Control Policy is provided for educational and informational purposes only. It is intended to offer healthcare
professionals guiding principles and policies regarding best practices in diversion control for patients who are prescribed
buprenorphine. This policy is not intended to establish a legal or medical standard of care. Healthcare professionals should
use their personal and professional judgment in interpreting these guidelines and applying them to the particular circum-
stances of their individual patients and practice arrangements. The information provided in this Policy is provided “as is”
with no guarantee as to its accuracy or completeness.
Preamble: Healthcare professionals can now treat up to 275 patients with buprenorphine. This increased access may contrib-
ute to increased diversion, misuse, and related harms. Signs that a patient is misusing or diverting buprenorphine include (1)
missed appointments; (2) requests for early reflls because pills were lost, stolen, or other reasons; (3) urine screens negative
for buprenorphine, positive for opioids; (4) claims of being allergic or intolerant to naloxone and requesting monotherapy;
(5) nonhealing or fresh track marks; or (5) police reports of selling on the streets. Likewise, there are a range of reasons for
diversion and misuse (e.g., diverting to family/friends with untreated opioid addiction with the intent of trying to “help”
convince them to also get treatment; diverting to family/friends on a treatment waiting list; selling some or all of the
medication to pay off old drug debts/purchase preferred opioid of misuse/pay for treatment in places where there are
inadequate addiction treatment professionals taking private insurance or Medicaid for such reasons as inadequate reim-
bursement/no reimbursement/burdensome prior authorization process).
The safety and health of patients and others in the community could be at risk if misuse and diversion are not addressed
proactively throughout treatment. The reputation of XYZ Medical Practice may also be put at risk.
Defnitions: Diversion is defned as the unauthorized rerouting or misappropriation of prescription medication to someone
other than for whom it was intended (including sharing or selling a prescribed medication); misuse includes taking medica-
tion in a manner, by route or by dose, other than prescribed.391
Purpose: Misuse and diversion should be defned and discussed with patients at the time of treatment entry; periodically
throughout treatment, particularly when there have been returns to illicit drug use; and when suspected (e.g., incorrect
buprenorphine pill/flm count) or confrmed. These procedures will establish the steps to be taken to prevent, monitor, and
respond to misuse and diversion of buprenorphine. The response should be therapeutic and matched to the patients’ needs,
as untreated opioid use disorder and treatment dropout/administrative discharges may lead to increased patient morbidity
and mortality and further use of diverted medications or illicit opioids associated with overdose death.
Procedures for Prevention:
• Use buprenorphine/naloxone combination products when medically indicated and cost is not an issue. Reserve
the daily buprenorphine monoproducts for pregnant patients and patients who could not afford treatment if the
combination product were required, who have a history of stability in treatment and low diversion risk, or who have
arrangements for observed dosing. Buprenorphine monoproducts are recommended for pregnant women.
• Counsel patients on safe storage of, and nonsharing of, medications. Patients must agree to safe storage of their
medication. This is even more critical if there are children in the home where the patient lives. Counsel patients
about acquiring locked devices and avoiding storage in parts of the home frequented by visitors (e.g., do not
recommend storage in the kitchen or common bathrooms). Proactively discuss how medication should be stored and
transported when traveling to minimize risk of unintended loss.
• Counsel patients on taking medication as instructed and not sharing medication. Explicitly explain to patients the
defnitions of diversion and misuse, with examples. Patients are required to take medication as instructed by the
healthcare professional; for example, they may not crush or inject the medication.
• Check the prescription drug monitoring program for new patients and check regularly thereafter. Prescription drug
monitoring program reports can be a useful resource when there is little history available or when there is a concern
based on observation. Check for prescriptions that interact with buprenorphine and for other buprenorphine
prescribers.
3-101
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
• Prescribe a therapeutic dose that is tailored to the patient’s needs. Do not routinely provide an additional supply
“just in case.” Question patients who say they need a signifcantly higher dose, particularly when they are already at
24 mg per day of buprenorphine equivalents.
• Make sure the patient understands the practice’s treatment agreement and prescription policies. The XYZ Medical
Practice’s treatment agreement and other documentation are clear about policies regarding number of doses in
each prescription, reflls, and rules on “lost” prescriptions. Review the policies in person with the patient. Offer an
opportunity for questions. Patient and provider must sign the agreement. Review the policies again with the patient
at subsequent appointments. See Sample Buprenorphine Treatment Agreement or Sample XR-NTX Treatment
Agreement as needed.
Procedures for Monitoring:
• Request random urine tests. The presence of buprenorphine in the urine indicates that the patient has taken some
portion of the prescribed dose. Absence of buprenorphine in the urine supports nonadherence. Testing for bu-
prenorphine metabolites (which are present only if buprenorphine is metabolized) should periodically be included to
minimize the possibility that buprenorphine is added directly to the urine sample. Dipstick tests can be subverted or
replaced. A range of strategies can be used to minimize falsifed urine collections, including (1) observed collection;
(2) disallowing carry-in items (e.g., purses, backpacks) in the bathroom; (3) turning off running water and coloring
toilet water to eliminate the possibility of dilution; (4) monitoring the bathroom door so that only one person can go
in; and (5) testing the temperature of the urine immediately after voiding.
• Schedule unannounced pill/flm counts. Periodically ask patients who are at high risk at initial or subsequent appoint-
ments to bring in their medication containers for a pill/flm count.
• With unannounced monitoring (both pill/flm counts and urine tests), the patient is contacted and must appear within
a specifed time period (e.g., 24 hours) after the phone call. If the patient doesn’t show, then the provider should
consider this as a positive indicator of misuse or diversion.
• Directly observe ingestion. Patients take medication in front of the healthcare professional or another qualifed
clinician and are observed until the medication dissolves in the mouth (transmucosal [sublingual or buccal] absorp-
tion). Patients who are having diffculty adhering to their buprenorphine can have their medication provided under
direct observation in the offce for a designated frequency (e.g., three times/week).
• Limit medication supply. When directly observed doses in the offce are not practical, short prescription time spans
can be used (e.g., weekly, 3 days at a time).
Procedures To Respond to Misuse or Diversion:
Misuse or diversion doesn’t mean automatic discharge from the practice. However, it will require consideration of one or
more of the following procedures:
• Evaluate the misuse and diversion. For instance, describe the incident of misuse (e.g., “the patient took the pre-
scribed dose on three or more occasions by intravenous route immediately after starting treatment, stating that she
believed the dose would not be adequate by sublingual route; she has just initiated treatment”) or diversion (“the
patient gave half of dose to his wife, who is still using heroin and was withdrawing, because he did not want her to
have to buy heroin off the street; she is on a waiting list for treatment”) and tailor the response to the behavior (e.g.,
reeducation of the patient on buprenorphine pharmacology in the frst example above; assistance with treatment
entry for the spouse in the second example). Reassess the treatment plan and patient progress. Strongly consider
smaller supplies of medication and supervised dosing for any patient who is taking medication intravenously or in-
tranasally or diverting, regardless of reason. Treatment structure may need to be increased, including more frequent
appointments, supervised administration, and increased psychosocial support.
• Intensify treatment or level of care, if needed. Some patients may require an alternative treatment setting or pharma-
cotherapy such as methadone. The clinician will discuss these alternatives with the patient to ensure optimal patient
outcome. This should be discussed at treatment onset so the patient is aware of the consequences of misuse and
diversion.
• Document and describe the misuse and diversion incident. Also document the clinical thinking that supports the
clinical response, which should be aimed at minimizing risk of diversion and misuse and treating the patient’s opioid
use disorder at the level of care needed.
Policy adapted from ASAM’s Offce-Based Opioid Use Disorder Policy and Procedure Manual, which is updated periodically;
the most current version is available online (www.asam.org/docs/default-source/advocacy/sample-diversion-policy
.pdf?sfvrsn=6).
Adapted with permission.392
This page intentionally left blank.
3-103
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Chapter 3F: Medical Management of
Patients Taking OUD Medications in
Hospital Settings
Chapter 3F guides the management of patients taking OUD medications in hospital
settings. The audience is healthcare professionals in emergency, general medical, surgical,
psychiatric, and obstetric units.
Patients with opioid use disorder (OUD) who
present to emergency departments (EDs) or
are admitted to hospitals for acute medical or
psychiatric care can beneft from medication
to treat OUD in the hospital setting. During
acute medical illness, patients experiencing
consequences of opioid use may be motivated
to change.393 Hospital-based providers can take
this opportunity to initiate long-term medication
maintenance.394,395
Unfortunately, less than one-quarter of patients
with an opioid-related hospitalization are offered
Food and Drug Administration-approved med-
ication for OUD within 30 days of discharge.396
Patients who already take OUD medication
may also present to the hospital. Thus, a broad
understanding of how to manage their OUD
medication during hospitalization is necessary.
The keys to effective patient management in
general hospital settings are:
• Balancing medication for OUD with other
medical concerns (e.g., surgery, pain manage-
ment) during hospitalization.
• Careful management after discharge.
• Seamless transfer to opioid treatment via
an opioid treatment program (OTP) or offce-
based opioid treatment (OBOT) provider after
discharge.
OPIOID-RELATED
inpatient hospital stays
INCREASED 119%
nationally from 2005 to 2017.397,398
Hospitalized or ED Patients Taking
Medication for OUD
Buprenorphine, methadone, and naltrexone may
be ordered in EDs or inpatient hospital units. It’s
essential for the patient to continue receiving
OUD medication while hospitalized.
Pain Management
Pain management for hospitalized patients
who take OUD medication is a key element of
medical management. Discuss pain manage-
ment and engage in a shared decision-making
process with patients being treated for OUD
with buprenorphine, methadone, or naltrexone.
3-104
Medications for Opioid Use Disorder TIP 63
Patients may have strong preferences and
opinions about pain and use of opioid analgesics
for pain treatment. Some patients may want to
avoid opioid analgesics. For others, inadequately
treated pain may be a trigger for illicit drug
use. Involve primary care pain specialists and
addiction treatment providers in discussing
options for managing OUD medication and pain
during patient hospitalization.
Buprenorphine
The hospital team will need to manage bu-
prenorphine for patients who present to the
ED or are hospitalized on buprenorphine main-
tenance. Physicians in inpatient settings can
legally order buprenorphine without a waiver
if a patient is admitted primarily for other
medical reasons.399 Key medication manage-
ment strategies include:
• Obtaining written consent to contact the
patient’s providers, including:
− Primary care provider.
− Buprenorphine prescriber.
− Pharmacy.
• Confrming the patient’s outpatient bu-
prenorphine dose by:
− Checking prescribing records.
− Contacting the prescriber or pharmacy.
− Examining recent prescription bottles.
− Checking the prescription drug monitoring
program database before administering
buprenorphine.
• Providing the usual daily dose to the patient,
once that dose is confrmed.
• Ensuring the patient’s outpatient prescriber
understands the reason for any missed visits.
• Informing the patient’s outpatient prescriber
that the patient may test positive for opioids
if treated with opioid analgesics while in the
hospital.
• Maintaining contact with the patient’s pre-
scriber, especially when a buprenorphine
dose change is considered and in discharge
planning.
Patients with pain may continue their
buprenorphine while in the hospital. For
mild-to-moderate pain, dividing the patient’s
usual buprenorphine dose three times per day
(TID) may provide suffcient pain relief.400 In
some cases, increased buprenorphine dose
may be appropriate. For moderate-to-severe
pain, additional analgesia will be necessary.
Two approaches to consider:
1. Continue buprenorphine treatment and
use full agonist opioids for added pain
relief. Because of the partial blockade
caused by buprenorphine, higher-than-usual
doses of opioids will probably be required
for pain relief. Fentanyl, hydromorphone,
and morphine have relatively high binding
affnities for the mu-opioid receptor and are
most likely to displace buprenorphine from
receptors and provide improved analgesia.
Once the painful condition has improved,
if mild-to-moderate pain persists, bu-
prenorphine can be divided TID to manage
residual pain. This approach is usually
successful and allows the patient to remain
stable on buprenorphine.
2. Discontinue buprenorphine upon hospi-
talization and use full agonist opioids to
treat pain and prevent withdrawal. This
approach avoids the blockade effect of
buprenorphine on the mu-opioid receptors
but leaves the patient vulnerable to a return
to illicit opioid use. It may be useful if the
frst approach does not achieve adequate
pain control.401 Consider a consult by an
addiction medicine, psychiatric, or pain
management provider if appropriate and
available.
Pregnant women on buprenorphine can
continue buprenorphine through their labor.
Labor pain for pregnant patients on buprenor-
phine can be managed effectively with epidural
analgesia or intravenous opioids. Spinal anes-
thesia is effective in patients on buprenorphine;
patients can receive general anesthesia if
needed.402
3-105
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Perioperative pain management of patients on
buprenorphine requires further study, but multiple
approaches have been found effective. Most
patients can continue buprenorphine through
the operative period. Treat postoperative
pain with regional anesthesia, nonopioid pain
management, or full agonist opioids. Remember
that higher doses are likely to be necessary. Some
data suggest that buprenorphine divided TID may
even be as effective as morphine for postopera-
tive pain control.403 Alternatively, buprenorphine
can be discontinued 72 hours before a planned
surgery and restarted after resolution of acute
postoperative pain. The risk of this approach is
that it leaves the patient vulnerable to a return
to use of illicit opioids.404
Methadone
The hospital team will need to manage
methadone for patients who present to
the ED or are hospitalized on methadone
maintenance treatment. This includes pregnant
women. Generally, only physicians in OTPs
can order methadone to treat OUD. However,
physicians in an inpatient setting can legally
order methadone administration to patients
admitted primarily for other reasons.405
Contact the patient’s OTP directly to confrm
the outpatient methadone dose, the last
day of dose administration, and whether
the patient was dispensed take-home doses
(and how many doses) after the last dose
administration at the OTP. This is to avoid
double dosing and to avoid providing a full
dose to a patient who hasn’t been to the OTP
for several days. Notify the OTP of the patient’s
admission and discharge so that OTP staff is
aware of:
• The patient’s upcoming missed visits.
• Medications received during hospitalization.
• Medications prescribed at discharge.
Patients in pain should receive their full usual
daily dose of methadone, barring contraindi-
cations. This is their baseline dose and should
not be considered a dose for pain management.
The expert panel for this
Treatment Improvement Protocol
(TIP) recommends restarting
buprenorphine before discharge
when possible, with a proper handoff
between inpatient and outpatient
providers.
They’ll need pain medication in addition to
their usual methadone dose. If their condition
is painful enough to require opioids, prescribe
short-acting opioids as scheduled, not as-
needed, treatment. Because these patients are
already opioid tolerant, they’ll likely require
higher doses of opioids than patients without
tolerance.406 However, as with any patient, use
nonopioid multimodal pain management when
possible to minimize reliance on opioids and
maximize pain control.407
CLINICAL CAUTION
Do Not Rely Solely on Patient Self-
Report of Methadone Dosage
Do not administer the methadone dose based
on patient self-report of OTP enrollment and
methadone dose; get OTP confrmation. This
is important because doses above 30 mg can
be lethal if the patient is not currently receiving
methadone treatment and has relatively low
tolerance to opioids. If it’s not possible to
confrm the patient’s methadone dose because
the OTP is closed on nights or weekends and
has no emergency contact, up to 20 mg per day
can be administered to treat opioid withdrawal
symptoms, but monitor for signs of opioid
intoxication. If the patient shows no signs of
sedation or opioid intoxication 3 to 4 hours
after the initial dose and continues to display
symptoms of withdrawal, an additional 5 mg to
10 mg may be safe to administer.
3-106
Medications for Opioid Use Disorder TIP 63
It is important to tell patients who receive
take-home doses that they should not take their
own medication while in the hospital. They will
receive methadone from the treatment team.
Patients can be asked to lock their take-home
medications with their other valuables. It is also
important to monitor these patients closely
after the initial and subsequent methadone
administration in the hospital. Some patients
who receive take-home doses do not take their
entire dose every day, so they may display signs
of intoxication or frank overdose if the hospital
staff gives them the full dose.
Naltrexone
Patients taking oral naltrexone for OUD
treatment may continue naltrexone when
admitted to the hospital if they do not have
and are not at risk for developing a painful
condition requiring opioid analgesia. Oral
naltrexone provides full blockade of opioid
receptors for up to 72 hours. Extended-release
injectable naltrexone (XR-NTX) provides mea-
surable naltrexone levels for 1 month or longer.
Thus, managing acute pain in patients taking
XR-NTX is complicated.
In patients who have taken naltrexone, manage
severe pain intensively via nonopioid approach-
es, such as regional anesthesia or injected non-
steroidal anti-infammatory drugs.
Naltrexone blockade can be overcome with
very high doses of opioids, but patients must be
closely monitored for respiratory depression in a
setting with anesthesia services. This is especially
true upon discontinuation of oral naltrexone,
which dissociates from opioid receptors.
Hospitalized or ED Patients Not
Taking Medication for OUD
Patients with OUD who present to the ED
or are admitted to the hospital for an acute
medical problem may beneft from initiating
medications for OUD during their hospital-
ization. A thoughtful and respectful discussion
of treatment options and patient-centered
provision of medication can be a critical entry
point into care. Research supports the effcacy
of initiating either buprenorphine or methadone
during acute hospital stays408,409 and starting
patients on buprenorphine in the ED.410
Buprenorphine Induction in the Hospital
Setting
Patients admitted to the hospital for medical
conditions incident to OUD can undergo
medically supervised withdrawal or receive
buprenorphine maintenance treatment
during their inpatient stay.411 It is important
to adequately address opioid withdrawal
because hospital patients may otherwise sign
out against medical advice or use illicit opioids
in the hospital. Buprenorphine can also be
initiated for maintenance treatment if there is
a system in place that allows smooth and reliable
discharge to an outpatient buprenorphine pre-
scriber. Unlike methadone, a several-day delay
between discharge and the frst visit to the out-
patient provider is acceptable for stable patients,
as long as suffcient medication is provided until
the patient begins outpatient treatment. The
prescription for medication to be taken outside
the hospital must be written by a prescriber with
a buprenorphine waiver. If there is no prescriber
with a waiver, it is possible to have a patient
return to the hospital ED or a clinic within the
hospital to have the buprenorphine dose admin-
istered by a physician (who does not need to be
waivered) for up to 3 days.
To provide continuity of care at discharge, use
these strategies:
• Develop and maintain a network of local
buprenorphine prescribers and other drug
treatment providers.
• Discharge patients directly to a specifc
outpatient prescriber for stabilization and
maintenance after inpatient buprenorphine
induction.
• Send discharge information directly to the
outpatient prescriber, including treatment
course, medications administered, and medi-
cations prescribed.
3-107
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
To initiate buprenorphine during hospitalization:
• Confrm that there are no contraindications to
buprenorphine before initiation.
• Discontinue opioids for pain management
only when no longer needed and the patient
is stable enough to tolerate withdrawal.
• Wait for patients to develop opioid withdraw-
al symptoms.
• Initiate buprenorphine treatment.
• Individualize buprenorphine dosing.
• Follow the dosing guidance found in Chapter
3D of this TIP.
A clinical trial found that starting buprenorphine
in the ED to treat OUD was more effective in
linking patients to buprenorphine treatment in
the community than were two other approaches
without medication.412 When patients presented
in opioid withdrawal, they received 8 mg of
buprenorphine in the ED. Patients who were not
in withdrawal received a detailed self-medication
guide and were provided buprenorphine for
an unobserved home induction. In both cases,
patients were given suffcient buprenorphine to
take 16 mg per day at home until they could see
an outpatient prescriber within 72 hours. Close
follow-up with an outpatient buprenorphine
prescriber was critical for dose stabilization and
ongoing medication management.
Methadone Induction in the Hospital
Setting
Offer to treat hospitalized patients in opioid
withdrawal with methadone (or buprenor-
phine) maintenance if they can continue
the medication in an OTP seamlessly after
discharge. Do not start patients on methadone
maintenance in the hospital without a clear
follow-up plan. Form relationships with local
OTPs that allow discharging of patients directly
into methadone maintenance treatment.
RESOURCE ALERT
Telehealth Tools for the Treatment
of OUD
The Substance Abuse and Mental Health
Services Administration and other federal
agencies have developed numerous resources
to guide healthcare professionals in their use
of telehealth and telemedicine approaches for
OUD. These resources include information on:
• Guidance on the use of telemedicine in OTPs
(https://store.samhsa.gov/product/Federal-
Guidelines-for-Opioid-Treatment-Programs/
PEP15-FEDGUIDEOTP).
• The policies that must be put in place (to
comply with the Controlled Substances Act)
by physicians who wish to use telehealth
in treating patients with buprenorphine for
OUD under the Drug Addiction Treatment
Act of 2000. Federal (and sometimes state)
restrictions apply, which can be reviewed by
accessing 21 USC § 802 (www.gpo.gov/fdsys
/pkg/USCODE-2011-title21/pdf/USCODE-2011
-title21-chap13-subchapI-partA-sec802.pdf).
• Centers for Medicare and Medicaid guidance
on telehealth (www.cms.gov/Medicare
/Medicare-General-Information/Telehealth
/index.html).
• Challenges and opportunities in using
telehealth for rural populations (https://
store.samhsa.gov/product/In-Brief-Rural-
Behavioral-Health-Telehealth-Challenges-
and-Opportunities/SMA16-4989).
• How certifed community behavioral health
clinics can use telehealth approaches to
expand their services (www.samhsa.gov
/section-223/care-coordination/telehealth
-telemedicine).
3-108
Medications for Opioid Use Disorder TIP 63
The TIP expert panel urges providers
not to force patients to withdraw
from opioid agonist treatment in the
hospital, especially if they have acute
illness, pain, or a mental illness.
Inpatient methadone inductions should follow
the same “start low, go slow” principles that
outpatient inductions do (see Chapter 3B of
this TIP). The initial dose should be from 10 mg
to 20 mg per day. Increase slowly by 5 mg every
few days in response to symptoms of opioid
withdrawal and level of sedation at the peak
plasma level 2 to 4 hours after dosing.
Naltrexone Induction in the Hospital
Setting
Consider XR-NTX initiation for patients who
complete withdrawal in the hospital and are
opioid free for 7 days (short acting) and up to 14
days (long acting). Only do so if:
• There are no contraindications (such as the
need for opioid analgesia).
• The patient prefers it after a risk/beneft
discussion that covers alternative treatments.
• There are available follow-up opportunities
for ongoing medication maintenance upon
discharge.
No published data indicate this approach’s
effectiveness.
If a patient desires and gives informed consent
for medically supervised withdrawal and XR-NTX
initiation while in the hospital, a frst dose of
naltrexone can be given before discharge. As
with other medications for OUD, discharge
coordination is critical. Hospitals that develop
XR-NTX induction protocols need to have a clear
discharge plan in place for patients who will then
need to continue treatment in the outpatient
setting. Patients should be advised about the
risk of overdose if return to opioid use occurs
after discontinuing treatment.
Medical Management Plan
The key to effective treatment is to involve
patients and all treating healthcare profes-
sionals in developing a comprehensive plan
for managing treatment with OUD medication
during and after hospitalization. This plan
should include:
• Strategies for pain management (if required).
• In-hospital dosing procedures.
• Postdischarge coordination of care with out-
patient programs and outpatient providers.
This plan ensures effective pain relief as well as
continuity of ongoing care for patients taking
medication for OUD.413
3-109
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
Notes
1 Department of Health and Human Services. (2016). The
opioid epidemic: By the numbers. Washington, DC:
Author.
2 Center for Behavioral Health Statistics and Quality. (2020).
Results from the 2019 National Survey on Drug Use and
Health: Detailed tables. Rockville, MD: Substance Abuse
and Mental Health Services Administration. Retrieved
April 28, 2021, from www.samhsa.gov/data/
3 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
4 Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A.,
Bailey, M. K., & O’Malley, L. (2017, January). Opioid-
related inpatient stays and emergency department visits
by state, 2009–2014. HCUP Statistical Brief No. 219.
Rockville, MD: Agency for Healthcare Research and
Quality.
5 Agency for Healthcare Research and Quality. (2020).
Rate of opioid-related ED visits per 100,000 population.
Retrieved April 28, 2021, from www.hcup-us.ahrq.gov/
faststats/OpioidUseMap?setting=ED
6 American Society of Addiction Medicine. (2011).
Defnition of addiction. Chevy Chase, MD: American
Society of Addiction Medicine. Retrieved January 5,
2018, from www.asam.org/resources/defnition
-of-addiction
7 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
8 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
9 Substance Abuse and Mental Health Services
Administration. (2016). Pocket guide: Medication-assisted
treatment of opioid use disorder. HHS Publication No.
(SMA) 16-4892PG. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
10 Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
11 Kreek, M. J., Borg, L., Ducat, E., & Ray, B. (2010).
Pharmacotherapy in the treatment of addiction:
Methadone. Journal of Addictive Diseases, 29(2),
200–216.
12 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
13 World Health Organization. (2015). 19th WHO model list
of essential medicines. Geneva, Switzerland: Author.
14 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
15 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., … Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence: A
randomized controlled trial. JAMA, 283(10), 1303–1310.
16 Nielsen, S., Larance, B., Degenhardt, L., Gowing,
L., Kehler, C., & Lintzeris, N. (2016). Opioid agonist
treatment for pharmaceutical opioid dependent people.
Cochrane Database of Systematic Reviews, 2016(5), 1–61.
17 Stoller, K. B., Stephens, M. A. C., & Schorr, A. (2016).
Integrated service delivery models for opioid treatment
programs in an era of increasing opioid addiction, health
reform, and parity. Retrieved October 16, 2017, from
www.aatod.org/wp-content/uploads/2016/07
/2nd-Whitepaper-.pdf
18 Comer, S. D., Sullivan, M. A., Yu, E., Rothenberg, J. L.,
Kleber, H. D., Kampman, K., … O’Brien, C. P. (2006).
Injectable, sustained-release naltrexone for the treatment
of opioid dependence: A randomized, placebo-controlled
trial. Archives of General Psychiatry, 63(2), 210–218.
19 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011). Injectable
extended-release naltrexone for opioid dependence: A
double-blind, placebo-controlled, multicentre randomised
trial. Lancet, 377(9776), 1506–1513.
20 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
21 American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
22 Lee, J. D., McDonald, R., Grossman, E., McNeely, J.,
Laska, E., Rotrosen, J., & Gourevitch, M. N. (2015).
Opioid treatment at release from jail using extended-
release naltrexone: A pilot proof-of-concept randomized
effectiveness trial. Addiction, 110(6), 1008–1014.
23 Leslie, D. L., Milchak, W., Gastfriend, D. R., Herschman, P.
L., Bixler, E. O., Velott, D. L., & Meyer, R. E. (2015). Effects
of injectable extended-release naltrexone (XR-NTX) for
opioid dependence on residential rehabilitation outcomes
and early follow-up. American Journal on Addictions,
24(3), 265–270.
24 Sullivan, M. A., Garawi, F., Bisaga, A., Comer, S. D.,
Carpenter, K., Raby, W. N., … Nunes, E. V. (2007).
Management of relapse in naltrexone maintenance for
heroin dependence. Drug and Alcohol Dependence,
91(2–3), 289–292.
3-110
Medications for Opioid Use Disorder TIP 63
25 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
26 World Health Organization. (2015). 19th WHO model list
of essential medicines. Geneva, Switzerland: Author.
27 Jaffe, J. H., & O’Keeffe, C. (2003). From morphine clinics
to buprenorphine: Regulating opioid agonist treatment
of addiction in the United States. Drug and Alcohol
Dependence, 70(2 Suppl.), S3–S11.
28 Department of Health and Human Services. (2021,
April 28). Practice guidelines for the administration
of buprenorphine for treating opioid use disorder.
HHS Notice, 86 Fed. Reg. 22439. Retrieved
May 21, 2021, from www.federalregister.gov/
documents/2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-for-treating-
opioid-use-disorder#:~:text=The%20Practice%20
Guidelines%20for%20the%20Administration%20
of%20Buprenorphine,counseling%20and%20other%20
ancillary%20services%20%28i.e.%2C%20psychosocial%20
services%29
29 Ling, W., Casadonte, P., Bigelow, G., Kampman, K.
M., Patkar, A., Bailey, G. L., … Beebe, K. L. (2010).
Buprenorphine implants for treatment of opioid
dependence: A randomized controlled trial. JAMA,
304(14), 1576–1583.
30 Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
31 Kinlock, T. W., Gordon, M. S., Schwartz, R. P., Fitzgerald,
T. T., & O’Grady, K. E. (2009). A randomized clinical trial
of methadone maintenance for prisoners: Results at
twelve-months post-release. Journal of Substance Abuse
Treatment, 37(3), 277–285.
32 McKenzie, M., Zaller, N., Dickman, S. L., Green, T. C.,
Parihk, A., Friedmann, P. D., & Rich, J. D. (2012). A
randomized trial of methadone initiation prior to release
from incarceration. Substance Abuse, 33(1), 19–29.
33 Gordon, M. S., Kinlock, T. W., Schwartz, R. P., O’Grady,
K. E., Fitzgerald, T. T., & Vocci, F. J. (2017). A randomized
trial of buprenorphine for prisoners: Findings at
12-months post-release. Drug and Alcohol Dependence,
172, 34–42.
34 Vocci, F. J., Schwartz, R. P., Wilson, M. E., Gordon, M. S.,
Kinlock, T. W., Fitzgerald, T. T., O’Grady, K. E., & Jaffe,
J. H. (2015). Buprenorphine dose induction in non-
opioid-tolerant pre-release prisoners. Drug and Alcohol
Dependence, 156, 133–138.
35 Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
36 Binder, T., & Vavrinková, B. (2008). Prospective
randomised comparative study of the effect of
buprenorphine, methadone and heroin on the course of
pregnancy, birthweight of newborns, early postpartum
adaptation and course of the neonatal abstinence
syndrome (NAS) in women followed up in the outpatient
department. Neuro Endocrinology Letters, 29(1), 80–86.
37 Fajemirokun-Odudeyi, O., Sinha, C., Tutty, S., Pairaudeau,
P., Armstrong, D., Phillips, T., & Lindow, S. W. (2006).
Pregnancy outcome in women who use opiates. European
Journal of Obstetrics & Gynecology and Reproductive
Biology, 126(2), 170–175.
38 Stimmel, B., & Adamsons, K. (1976). Narcotic
dependency in pregnancy. Methadone maintenance
compared to use of street drugs. JAMA, 235, 1121–1124.
39 Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
40 Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
41 American College of Obstetricians and Gynecologists
Committee Opinion. (2017, August). Opioid use and
opioid use disorder in pregnancy. Number 711.
42 Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
43 American College of Obstetricians and Gynecologists
Committee Opinion. (2017, August). Opioid use and
opioid use disorder in pregnancy. Number 711.
44 American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
45 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2).
CD002207.
3-111
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
46 Lee, J. D., Nunes, E. V., Jr., Novo, P., Bachrach, K., Bailey,
G. L., Bhatt, S., … Rotrosen, J. (2018). Comparative
effectiveness of extended-release naltrexone versus
buprenorphine-naloxone for opioid relapse prevention
(X:BOT): A multicentre, open-label, randomised
controlled trial. Lancet, 391(10118), 309–318.
47 Tanum, L., Solli, K. K., Latif, Z. E., Benth, J. Š., Opheim,
A., Sharma-Haase, K., … Kunøe, N. (2017). The
effectiveness of injectable extended-release naltrexone vs
daily buprenorphine-naloxone for opioid dependence: A
randomized clinical noninferiority trial. JAMA Psychiatry,
74(12), 1197–1205.
48 Department of Veterans Affairs & Department of
Defense. (2015). VA/DoD clinical practice guideline for
the management of substance use disorders. Retrieved
October 16, 2017, from www.healthquality.va.gov
/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf
49 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., … Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence: A
randomized controlled trial. JAMA, 283(10), 1303–1310.
50 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
51 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
52 Gowing, L., Ali, R., White, J. M., & Mbewe, D. (2017).
Buprenorphine for managing opioid withdrawal.
Cochrane Database of Systematic Reviews, 2017(2).
CD002025.
53 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
54 Hser, Y. I., Huang, D., Saxon, A. J., Woody, G., Moskowitz,
A. L., Matthews, A. G., & Ling, W. (2017). Distinctive
trajectories of opioid use over an extended follow-up of
patients in a multisite trial on buprenorphine + naloxone
and methadone. Journal of Addiction Medicine, 11(1),
63–69.
55 Novick, D. M., Salsitz, E. A., Joseph, H., & Kreek, M.
J. (2015). Methadone medical maintenance: An early
21st-century perspective. Journal of Addictive Diseases,
34(2–3), 226–237.
56 Fiellin, D. A., Moore, B. A., Sullivan, L. E., Becker, W.
C., Pantalon, M. V., Chawarski, M. C., … Schottenfeld,
R. S. (2008). Long-term treatment with buprenorphine/
naloxone in primary care: Results at 2-5 years. American
Journal on Addictions, 17(2), 116–120.
57 Krupitsky, E., Nunes, E. V., Ling, W., Gastfriend, D. R.,
Memisoglu, A., & Silverman, B. L. (2013). Injectable
extended-release naltrexone (XR-NTX) for opioid
dependence: long-term safety and effectiveness.
Addiction, 108(9), 162–1637.
58 Kreek, M. J., Levran, O., Reed, B., Schlussman, S. D.,
Zhou, Y., & Butelman, E. R. (2012). Opiate addiction and
cocaine addiction: Underlying molecular neurobiology
and genetics. Journal of Clinical Investigation, 122(10),
3387–3393.
59 Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016).
Neurobiologic advances from the brain disease model
of addiction. New England Journal of Medicine, 374(4),
363–371.
60 Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter,
J., Thomas, C., … Bilangi, R. (2009). Buprenorphine
tapering schedule and illicit opioid use. Addiction, 104(2),
256–265.
61 Senay, E. C., Dorus, W., & Thornton, W. (1977).
Withdrawal from methadone maintenance: Rate of
withdrawal and expectation. Archives of General
Psychiatry, 34(3), 361–367.
62 Sigmon, S. C., Dunn, K. E., Saulsgiver, K., Patrick, M.
E., Badger, G. J., Heil, S. H., … Higgins, S. T. (2013). A
randomized, double-blind evaluation of buprenorphine
taper duration in primary prescription opioid abusers.
JAMA Psychiatry, 70(12), 1347–1354.
63 Department of Veterans Affairs & Department of
Defense. (2015). VA/DoD clinical practice guideline for
the management of substance use disorders. Retrieved
October 16, 2017, from www.healthquality.va.gov
/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf
64 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., … Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
65 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
66 Amato, L., Davoli, M., Minozzi, S., Ferroni, E., Ali, R., &
Ferri M. (2013). Methadone at tapered doses for the
management of opioid withdrawal. Cochrane Database
of Systematic Reviews, 2013(2). CD003409.
3-112
Medications for Opioid Use Disorder TIP 63
67 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
68 Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter,
J., Thomas, C., & Bilangi, R. (2009). Buprenorphine
tapering schedule and illicit opioid use. Addiction, 104(2),
256–265.
69 Amato, L., Minozzi, S., Davoli, M., & Vecchi, S. (2011).
Psychosocial and pharmacological treatments versus
pharmacological treatments for opioid detoxifcation.
Cochrane Database of Systematic Reviews, 2011(9).
CD005031.
70 Nunes, E. V., Gordon, M., Friedmann, P. D., Fishman,
M. J., Lee, J. D., Chen, D. T., … O’Brien, C. P. (2018).
Relapse to opioid use disorder after inpatient treatment:
Protective effect of injection naltrexone. Journal of
Substance Abuse Treatment, 85, 49–55.
71 Satoh, M., & Minami, M. (1995). Molecular pharmacology
of the opioid receptors. Pharmacology
& Therapeutics, 68(3), 343–364.
72 Akbarali, H. I., Inkisar, A., & Dewey, W. L. (2014). Site and
mechanism of morphine tolerance in the gastrointestinal
tract. Neurogastroenterology and Motility, 26(10),
1361–1367.
73 Bodnar, R. J. (2017). Endogenous opiates and behavior,
2015. Peptides, 88, 126–188.
74 Johnson, R. E., Strain, E. C., & Amass, L. (2003).
Buprenorphine: How to use it right. Drug and Alcohol
Dependence, 70(Suppl.), S59–S77.
75 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(2). CD001333.
76 Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
77 Kreek, M. J., Borg, L., Ducat, E., & Ray, B. (2010).
Pharmacotherapy in the treatment of addiction:
Methadone. Journal of Addictive Diseases, 29(2),
200–216.
78 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
79 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
80 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
81 Metzger, D. S., Woody, G. E., McLellan, A. T., O’Brien,
C. P., Druley, P., Navaline, H., … Abrutyn, E. J. (1993).
Human immunodefciency virus seroconversion among
intravenous drug users in- and out-of-treatment: An
18-month prospective follow-up. Journal of Acquired
Immune Defciency Syndromes, 6(9), 1049–1056.
82 Ball, J. C., & Ross, A. (1991). The effectiveness of
methadone maintenance treatment. New York, NY:
Springer Verlag.
83 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2).
CD002207.
84 Walsh, S. L., & Strain, E. C. (2006). Pharmacology of
methadone. In E. C. Strain & M. L. Stitzer (Eds.), The
treatment of opioid dependence (pp. 59–76). Baltimore,
MD: John Hopkins University Press.
85 Mallinckrodt Pharmaceuticals. (2017). Label: Methadose -
methadone hydrochloride concentrate; Methadose sugar-
free- methadone hydrochloride concentrate. Retrieved
January 9, 2018, from https://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=808a9d0b
-720b-4034-a862-5122ff514608
86 Walsh, S. L., & Strain, E. C. (2006). Pharmacology of
methadone. In E. C. Strain & M. L. Stitzer (Eds.), The
treatment of opioid dependence (pp. 59–76). Baltimore,
MD: John Hopkins University Press.
87 Payte, J. T., & Zweben, J. E. (1998). Opioid maintenance
therapies. In A. W. Graham, T. K. Schultz, & B. B. Wilford
(Eds.), Principles of addiction medicine (pp. 557–570).
Chevy Chase, MD: American Society of Addiction
Medicine.
88 Eap, C. B., Buclin, T., & Baumann, P. (2002). Interindividual
variability of the clinical pharmacokinetics of methadone:
Implications for the treatment of opioid dependence.
Clinical Pharmacokinetics, 41(14), 1153–1193.
89 Mallinckrodt Pharmaceuticals. (2017). Label: Methadose -
methadone hydrochloride concentrate; Methadose sugar-
free- methadone hydrochloride concentrate. Retrieved
January 9, 2018, from https://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=808a9d0b
-720b-4034-a862-5122ff514608
90 Oda, Y., & Kharasch, E. D. (2001). Metabolism of
methadone and levo-alpha-acetylmethadol (LAAM)
by human intestinal cytochrome P450 3A4 (CYP3A4):
Potential contribution of intestinal metabolism to
presystemic clearance and bioactivation. Journal of
Pharmacology and Experimental Therapeutics, 298(3),
1021–1032.
3-113
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
91 Eap, C. B., Buclin, T., & Baumann, P. (2002). Interindividual
variability of the clinical pharmacokinetics of methadone:
Implications for the treatment of opioid dependence.
Clinical Pharmacokinetics, 41(14), 1153–1193.
92 Eap, C. B., Buclin, T., & Baumann, P. (2002). Interindividual
variability of the clinical pharmacokinetics of methadone:
Implications for the treatment of opioid dependence.
Clinical Pharmacokinetics, 41(14), 1153–1193.
93 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
94 Federal opioid treatment standards, 42 CFR § 8.12
(2015).
95 Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
96 Baxter, L. E., Sr., Campbell, A., Deshields, M., Levounis,
P., Martin, J. A., McNicholas, L., … Wilford, B. B. (2013).
Safe methadone induction and stabilization: Report of
an expert panel. Journal of Addiction Medicine, 7(6),
377–386.
97 Food and Drug Administration. (2016, March). FDA
Drug Safety Communications, FDA urges caution about
withholding opioid addiction medications from patients
taking benzodiazepines or CNS depressant: Careful
medication management can reduce risks. Retrieved
January 3, 2018, from www.fda.gov/downloads/Drugs
/DrugSafety/UCM576377.pdf
98 Lintzeris, N., & Nielsen, S. (2010). Benzodiazepines,
methadone and buprenorphine: Interactions and clinical
management. American Journal on Addictions, 19(1),
59–72.
99 Bart, G., Wyman, Z., Wang, Q., Hodges, J. S., Karim, R.,
& Bart, B. A. (2017). Methadone and the QTc interval:
Paucity of clinically signifcant factors in a retrospective
cohort. Journal of Addiction Medicine, 11(6), 489–493.
100Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
101Bednar, M. M., Harrigan, E. P., & Ruskin, J. N. (2002).
Torsades de pointes associated with nonantiarrhythmic
drugs and observations on gender and QTc. American
Journal of Cardiology, 89(11), 1316–1319.
102Al-Khatib, S. M., LaPointe, N. M. A., Kramer, J. M., &
Califf, R. M. (2003). What clinicians should know about
the QT interval. JAMA, 289(16), 2120–2127.
103Martin, J. A., Campbell, A., Killip, T., Kotz, M., Krantz,
M. J., Kreek, M. J., … Wilford, B. B. (2011). QT interval
screening in methadone maintenance treatment:
Report of a SAMHSA expert panel. Journal of Addictive
Diseases, 30(4), 283–306.
104Bazett, H. C. (1997). An analysis of the time-relations
of electrocardiograms. Annals of Noninvasive
Electrocardiology, 2(2), 177–194.
105Martin, J. A., Campbell, A., Killip, T., Kotz, M., Krantz,
M. J., Kreek, M. J., … Wilford, B. B. (2011). QT interval
screening in methadone maintenance treatment:
Report of a SAMHSA expert panel. Journal of Addictive
Diseases, 30(4), 283–306.
106Mallinckrodt Pharmaceuticals. (2015). Methadose™
dispersible tablets, 40 mg (Methadone hydrochloride
tablets for oral suspension USP), CII - Generic products.
Retrieved October 16, 2017, from https://dailymed.nlm
.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid
=8731
107Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
108Krantz, M. J., Martin, J., Stimmel, B., Mehta, D.,
& Haigney, M. C. (2009). QTc interval screening in
methadone treatment. Annals of Internal Medicine,
150(6), 387–395.
109Bart, G., Wyman, Z., Wang, Q., Hodges, J. S., Karim, R.,
& Bart, B. A. (2017). Methadone and the QTc interval:
Paucity of clinically signifcant factors in a retrospective
cohort. Journal of Addiction Medicine, 11(6), 489–493.
110Pani, P. P., Trogu, E., Maremmani, I., & Pacini, M. (2013).
QTc interval screening for cardiac risk in methadone
treatment of opioid dependence. Cochrane Database of
Systematic Reviews, 2013(6). CD008939.
111Martin, J. A., Campbell, A., Killip, T., Kotz, M., Krantz,
M. J., Kreek, M. J., … Wilford, B. B. (2011). QT interval
screening in methadone maintenance treatment:
Report of a SAMHSA expert panel. Journal of Addictive
Diseases, 30(4), 283–306.
112Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
113Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
3-114
Medications for Opioid Use Disorder TIP 63
114Jones, H. E., Dengler, E., Garrison, A., O’Grady, K.
E., Seashore, C., Horton, E., … Thorp, J. (2014).
Neonatal outcomes and their relationship to maternal
buprenorphine dose during pregnancy. Drug and Alcohol
Dependence, 134, 414–417.
115Cleary, B. J., Reynolds, K., Eogan, M., O’Connell, M.
P., Fahey, T., Gallagher, P. J., … Murphy, D. J. (2014).
Methadone dosing and prescribed medication use in
a prospective cohort of opioid-dependent pregnant
women. Addiction, 108(4), 762–770.
116Kaltenbach, K., Holbrook, A. M., Coyle, M. G., Heil,
S. H., Salisbury, A. L., Stine, S. M., … Jones, H. E. (2012).
Predicting treatment for neonatal abstinence syndrome
in infants born to women maintained on opioid agonist
medication. Addiction, 107(Suppl. 1), 45–52.
117Food and Drug Administration. (2016, March). FDA Drug
Safety Communication: FDA warns about several safety
issues with opioid pain medicines; requires label changes.
118McCance-Katz, E. F., Sullivan, L. E., & Nallani, S. (2010).
Drug interactions of clinical importance among the
opioids, methadone and buprenorphine, and other
frequently prescribed medications: A review. American
Journal on Addictions, 19(1), 4–16.
119Martin, J., Zweben, J. E., & Payte, J. T. (2014). Opioid
maintenance treatment. In R. K. Ries, D. A. Fiellin, S. C.
Miller, & R. Saitz (Eds.), The ASAM principles of addiction
medicine (5th ed., pp. 759–777). Philadelphia, PA:
Wolters Kluwer Health.
120Saxon, A. J., & Miotto, K. (2011). Methadone
maintenance. In P. Ruiz & E. Strain (Eds.), Lowinson
and Ruiz’s substance abuse: A comprehensive textbook
(5th ed., pp. 419–436). Philadelphia, PA: Wolters Kluwer
Health.
121McCance-Katz, E. F., Rainey, P. M., Jatlow, P., & Friedland,
G. (1998). Methadone effects on zidovudine disposition
(AIDS Clinical Trials Group 262). Journal of Acquired
Immune Defciency Syndromes and Human Retrovirology,
18(5), 435–443.
122World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment of
opioid dependence. Geneva, Switzerland: WHO Press.
123American College of Obstetricians and Gynecologists
Committee Opinion. (2017, August). Opioid use and
opioid use disorder in pregnancy. Number 711.
124Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
125U.S. Preventive Services Task Force. (2019).
Final Recommendation Statement on Human
Immunodefciency Virus (HIV) Infection:
Screening. Retrieved June 11, 2019, from www.
uspreventiveservicestaskforce.org/Page/
Document/RecommendationStatementFinal/
human-immunodefciency-virus-hiv-infection-screening
126Centers for Disease Control and Prevention. Testing
Recommendations for Hepatitis C Virus Infection.
October 15, 2015. Retrieved from www.cdc.gov/
hepatitis/hcv/guidelinesc.htm
127Centers for Disease Control and Prevention. (2016). Viral
hepatitis. Retrieved December 1, 2017, from
www.cdc.gov/hepatitis/hbv/bfaq.htm
128Baxter, L. E., Sr., Campbell, A., Deshields, M., Levounis,
P., Martin, J. A., McNicholas, L., … Wilford, B. B. (2013).
Safe methadone induction and stabilization: Report of
an expert panel. Journal of Addiction Medicine, 7(6),
377–386.
129McCance-Katz, E. F., Sullivan, L. E., & Nallani, S. (2010).
Drug interactions of clinical importance among the
opioids, methadone and buprenorphine, and other
frequently prescribed medications: A review. American
Journal on Addictions, 19(1), 4–16.
130Baxter, L. E., Sr., Campbell, A., Deshields, M., Levounis,
P., Martin, J. A., McNicholas, L., … Wilford, B. B. (2013).
Safe methadone induction and stabilization: Report of
an expert panel. Journal of Addiction Medicine, 7(6),
377–386.
131Jones, H. E. (2004). Practical considerations for the
clinical use of buprenorphine. Science and Practice
Perspectives, 2(2), 4–20.
132Vocci, F. J., Schwartz, R. P., Wilson, M. E., Gordon, M.
S., Kinlock, T. W., Fitzgerald, T. T., … Jaffe, J. H. (2015).
Buprenorphine dose induction in non-opioid-tolerant
pre-release prisoners. Drug and Alcohol Dependence,
156, 133–138.
133Kinlock, T. W., Gordon, M. S., Schwartz, R. P., & O’Grady,
K. E. (2008). A study of methadone maintenance for
male prisoners: 3-month postrelease outcomes. Criminal
Justice and Behavior, 35(1), 34–47.
134Martin, J., Zweben, J. E., & Payte, J. T. (2014). Opioid
maintenance treatment. In R. K. Ries, D. A. Fiellin, S. C.
Miller, & R. Saitz (Eds.), The ASAM principles of addiction
medicine (5th ed., pp. 759–777). Philadelphia, PA:
Wolters Kluwer.
135Baxter, L. E., Sr., Campbell, A., Deshields, M., Levounis,
P., Martin, J. A., McNicholas, L., … Wilford, B. B. (2013).
Safe methadone induction and stabilization: Report of
an expert panel. Journal of Addiction Medicine, 7(6),
377–386.
136Center for Substance Abuse Treatment. (1993). State
methadone treatment guidelines. HHS Publication No.
(SMA) 93-1991. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
3-115
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
137Chou, R., Cruciani, R. A., Fiellin, D. A., Compton,
P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014).
Methadone safety: A clinical practice guideline from the
American Pain Society and College on Problems of Drug
Dependence, in collaboration with the Heart Rhythm
Society. Journal of Pain, 15(4), 321–337.
138Gowing, L., Ali, R., Dunlop, A., Farrell, M., & Lintzeris,
N. (2014). National guidelines for medication-assisted
treatment of opioid dependence. Retrieved January 4,
2018, from www.health.gov.au/sites/default/fles/national-
guidelines-for-medication-assisted-treatment-of-opioid-
dependence.pdf
139Leavitt, S. B., Shinderman, M., Maxwell, S., Eap, C. B.,
& Paris, P. (2000). When “enough” is not enough: New
perspectives on optimal methadone maintenance dose.
Mount Sinai Journal of Medicine, 67(5–6), 404–411.
140Payte, J. T. (2002). Opioid agonist treatment of addiction.
Slide presentation at ASAM Review Course in Addiction
Medicine.
141Leavitt, S. B. (2003). The methadone dose debate
continues. Addiction Treatment Forum, 12(1), 1,3.
142Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
143Benmebarek, M., Devaud, C., Gex-Fabry, M., Powell
Golay, K., Brogli, C., Baumann, P., … Eap, C. B. (2004).
Effects of grapefruit juice on the pharmacokinetics of the
enantiomers of methadone. Clinical Pharmacology and
Therapeutics, 76(1), 55–63.
144Drozdick, J., III, Berghella, V., Hill, M., & Kaltenbach,
K. (2002). Methadone trough levels in pregnancy.
American Journal of Obstetrics and Gynecology, 187(5),
1184–1188.
145Leavitt, S. B., Shinderman, M., Maxwell, S., Eap, C. B.,
& Paris, P. (2000). When “enough” is not enough: New
perspectives on optimal methadone maintenance dose.
Mount Sinai Journal of Medicine, 67(5–6), 404–411.
146Hallinan, R., Ray, J., Byrne, A., Agho, K., & Attia, J. (2006).
Therapeutic thresholds in methadone maintenance
treatment: A receiver operating characteristic analysis.
Drug and Alcohol Dependence, 81, 129–136.
147Stine, S. M., & Kosten, T. R. (2014). Pharmacologic
interventions for opioid dependence. In R. K. Ries,
D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.), The ASAM
principles of addiction medicine (5th ed., pp. 745–758).
Philadelphia, PA: Wolters Kluwer.
148Drozdick, J., III, Berghella, V., Hill, M., & Kaltenbach,
K. (2002). Methadone trough levels in pregnancy.
American Journal of Obstetrics and Gynecology, 187(5),
1184–1188.
149Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
150Food and Drug Administration. (2008). Methadose™ oral
concentrate. Retrieved October 16, 2017, from www.
accessdata.fda.gov/drugsatfda_docs/label/2008
/017116s021lbl.pdf
151Department of Veterans Affairs & Department of
Defense. (2015). VA/DoD clinical practice guideline for
the management of substance use disorders. Retrieved
October 16, 2017, from www.healthquality.va.gov
/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf
152Stitzer, M. L., Iguchi, M. Y., & Felch, L. J. (1992).
Contingent take-home incentive: Effects on drug use of
methadone maintenance patients. Journal of Consulting
and Clinical Psychology, 60(6), 927–934.
153Gwin Mitchell, S., Kelly, S. M., Brown, B. S., Schacht
Reisinger, H., Peterson, J. A., Ruhf, A., … Schwartz, R. P.
(2009). Uses of diverted methadone and buprenorphine
by opioid-addicted individuals in Baltimore, Maryland.
American Journal on Addictions, 18(5), 346–355.
154Vlahov, D., O’Driscoll, P., Mehta, S. H., Ompad, D. C.,
Gern, R., Galai, N., & Kirk, G. D. (2007). Risk factors for
methadone outside treatment programs: Implications for
HIV treatment among injection drug users. Addiction,
102(5), 771–777.
155Timko, C., Schultz, N. R., Cucciare, M. A., Vittorio, L.,
& Garrison-Diehn, C. (2016). Retention in medication-
assisted treatment for opiate dependence: A systematic
review. Journal of Addictive Diseases, 35(1), 22–35.
156Woody, G. E., Kane, V., Lewis, K., & Thompson, R. (2007).
Premature deaths after discharge from methadone
maintenance: A replication. Journal of Addiction
Medicine, 1(4), 180–185.
157Sordo, L., Barrio, G., Bravo, M. J., Indave, I., Degenhardt,
L., Wiessing, L., Ferri, M., & Pastor-Barriuso, R. (2017).
Mortality risk during and after opioid substitution
treatment: Systematic review and meta-analysis of cohort
studies. BMJ, 357, j1550.
158Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
159Schwartz, R. P., Highfeld, D. A., Jaffe, J. H., Brady, J.
V., Butler, C. B., Rouse, C. O., … Battjes, R. J. (2006).
A randomized controlled trial of interim methadone
maintenance. Archives of General Psychiatry, 63(1),
102–109.
3-116
Medications for Opioid Use Disorder TIP 63
160Yancovitz, S. R., Des Jarlais, D. C., Peyser, N. P., Drew, E.,
Friedmann, P., Trigg, H. L., & Robinson, J. W. (1991). A
randomized trial of an interim methadone maintenance
clinic. American Journal of Public Health, 81(9),
1185–1191.
161Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
162Martin, W. R., Jasinski, D. R., & Mansky, P. A. (1973).
Naltrexone, an antagonist for the treatment of heroin
dependence: Effects in man. Archives of General
Psychiatry, 28(6), 784–791.
163Sullivan, M. A., Garawi, F., Bisaga, A., Comer, S. D.,
Carpenter, K., Raby, W. N., … Nunes, E. V. (2007).
Management of relapse in naltrexone maintenance for
heroin dependence. Drug and Alcohol Dependence,
91(2–3), 289–292.
164American Society of Addiction Medicine. (2015). National
practice guideline for the use of medications in the
treatment of addiction involving opioid use. Retrieved
December 1, 2017, from www.asam.org
/docs/default-source/practice-support/guidelines-and
-consensus-docs/asam-national-practice-guideline
-supplement.pdf?sfvrsn=24
165Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane
Database of Systematic Reviews, 2011(2), 1–45.
doi:10.1002/14651858.CD001333.pub3
166Alkermes. (2015). Vivitrol. Retrieved May 21, 2017, from
http://medlibrary.org/lib/rx/meds/vivitrol/page/6
167Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011). Injectable
extended-release naltrexone for opioid dependence: A
double-blind, placebo-controlled, multicentre randomised
trial. Lancet, 377(9776), 1506–1513.
168Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
169Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfriend, D. R., & Silverman, B. L. (2011, April 30).
Injectable extended-release naltrexone for opioid
dependence: A double-blind, placebo-controlled,
multicentre randomised trial. Lancet, 377(9776),
1506–1513.
170Lee, J. D., Nunes, E. V., Jr., Novo, P., Bachrach, K., Bailey,
G. L., Bhatt, S., … Rotrosen J. (2018). Comparative
effectiveness of extended-release naltrexone versus
buprenorphine-naloxone for opioid relapse prevention
(X:BOT): A multicentre, open-label, randomised
controlled trial. Lancet, 391(10118), 309–318.
171Tanum, L., Solli, K. K., Latif, Z. E., Benth, J. Š., Opheim,
A., Sharma-Haase, K., … Kunøe, N. (2017). The
effectiveness of injectable extended-release naltrexone vs
daily buprenorphine-naloxone for opioid dependence: A
randomized clinical noninferiority trial. JAMA Psychiatry,
74(12), 1197–1205.
172Meyer, M. C., Straughn, A. B., Lo, M. W., Schary, W.
L., & Whitney, C. C. (1984). Bioequivalence, dose-
proportionality, and pharmacokinetics of naltrexone after
oral administration. Journal of Clinical Psychiatry, 45(9 Pt
2), 15–19.
173Alkermes. (2015). Vivitrol (naltrexone for extended
release injectable suspension) 380 mg/vial. Retrieved
January 9, 2018, from www.vivitrol.com/content
/pdfs/prescribing-information.pdf
174Alkermes. (2015). Vivitrol (naltrexone for extended
release injectable suspension) 380 mg/vial. Retrieved
January 9, 2018, from www.vivitrol.com/content
/pdfs/prescribing-information.pdf
175Meyer, M. C., Straughn, A. B., Lo, M. W., Schary, W.
L., & Whitney, C. C. (1984). Bioequivalence, dose-
proportionality, and pharmacokinetics of naltrexone after
oral administration. Journal of Clinical Psychiatry, 45(9, Pt.
2), 15–19.
176Bigelow, G. E., Preston, K. L., Schmittner, J., Dong, Q.,
& Gastfriend, D. R. (2012). Opioid challenge evaluation
of blockade by extended-release naltrexone in opioid-
abusing adults: Dose-effects and time-course. Drug and
Alcohol Dependence, 123(1–3), 57–65.
177Tetrault, J. M., Tate, J. P., McGinnis, K. A., Goulet, J. L.,
Sullivan, L. E., Bryant, K., … Fiellin, D. A. (2012). Hepatic
safety and antiretroviral effectiveness in HIV-infected
patients receiving naltrexone. Alcoholism: Clinical and
Experimental Research, 36(2), 318–324.
178Comer, S. D., Mannelli, P., Alam, D., Douaihy, A., Nangia,
N., Akerman, S. C., ... Sullivan, M. A. (2020). Transition of
patients with opioid use disorder from buprenorphine to
extended-release naltrexone: A randomized clinical trial
assessing two transition regimens. American Journal on
Addictions, 29(4), 313–322.
179Bisaga, A., Mannelli, P., Yu, M., Nangia, N., Graham, C.
E., Tompkins, D. A., ... Sullivan, M. A. (2018). Outpatient
transition to extended-release injectable naltrexone for
patients with opioid use disorder: A phase 3 randomized
trial. Drug and Alcohol Dependence, 187, 171–178.
180Comer, S. D., Mannelli, P., Alam, D., Douaihy, A., Nangia,
N., Akerman, S. C., ... Sullivan, M. A. (2020). Transition of
patients with opioid use disorder from buprenorphine to
extended-release naltrexone: A randomized clinical trial
assessing two transition regimens. American Journal on
Addictions, 29(4), 313–322.
181Jones, H. E., Kaltenbach, K., Heil, S. H., Stine, S. M.,
Coyle, M. G., Arria, A. M., … Fischer, G. (2010). Neonatal
abstinence syndrome after methadone or buprenorphine
exposure. New England Journal of Medicine, 363(24),
2320–2331.
3-117
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
182Mozurkewich, E. L., & Rayburn, W. F. (2014).
Buprenorphine and methadone for opioid addiction
during pregnancy. Obstetrics and Gynecology Clinics
of North America, 41(2), 241–253.
183Alkermes. (2015). Vivitrol. Retrieved October 16, 2017,
from http://medlibrary.org/lib/rx/meds/vivitrol/page/6
184Bisaga, A., Mannelli, P., Yu, M., Nangia, N., Graham, C.
E., Tompkins, D. A., ... Sullivan, M. A. (2018). Outpatient
transition to extended-release injectable naltrexone for
patients with opioid use disorder: A phase 3 randomized
trial. Drug and Alcohol Dependence, 187, 171–178.
185Comer, S. D., Mannelli, P., Alam, D., Douaihy, A., Nangia,
N., Akerman, S. C., ... Sullivan, M. A. (2020). Transition of
patients with opioid use disorder from buprenorphine to
extended-release naltrexone: A randomized clinical trial
assessing two transition regimens. American Journal on
Addictions, 29(4), 313–322.
186Sullivan, M., Bisaga, A., Pavlicova, M., Choi, C. J.,
Mishlen, K., Carpenter, K. M., … Nunes, E. V. (2017).
Long-acting injectable naltrexone induction: A
randomized trial of outpatient opioid detoxifcation with
naltrexone versus buprenorphine. American Journal of
Psychiatry, 174(5), 459–467.
187Tetrault, J. M., Tate, J. P., McGinnis, K. A., Goulet, J. L.,
Sullivan, L. E., Bryant, K., … Fiellin, D. A. (2012). Hepatic
safety and antiretroviral effectiveness in HIV-infected
patients receiving naltrexone. Alcoholism: Clinical and
Experimental Research, 36(2), 318–324.
188Crowley, T. J., Wagner, J. E., Zerbe, G., & Macdonald,
M. (1985). Naltrexone-induced dysphoria in former
opioid addicts. American Journal of Psychiatry, 142(9),
1081–1084.
189Miotto, K., McCann, M., Basch, J., Rawson, R., & Ling,
W. (2002). Naltrexone and dysphoria: Fact or myth?
American Journal on Addictions, 11(2), 151–160.
190Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
191National Library of Medicine. (2014). NALTREXONE
HYDROCHLORIDE - naltrexone hydrochloride tablet, flm
coated DAILY MED. Retrieved October 16, 2017, from
https://dailymed.nlm.nih.gov/dailymed/drugInfo
.cfm?setid=06ff2d5a-e62b-4fa4-bbdb-01938535bc65
192Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
193Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
194Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
195U.S. Preventive Services Task Force. (2019).
Final Recommendation Statement on Human
Immunodefciency Virus (HIV) Infection:
Screening. Retrieved January 11, 2020, from
www.uspreventiveservicestaskforce.org/Page/
Document/RecommendationStatementFinal/
human-immunodefciency-virus-hiv-infection-screening
196Centers for Disease Control and Prevention. Testing
Recommendations for Hepatitis C Virus Infection.
October 15, 2015. Retrieved January 11, 2020, from
www.cdc.gov/hepatitis/hcv/guidelinesc.htm
197Centers for Disease Control and Prevention. (2016). Viral
hepatitis. Retrieved October 16, 2017, from
www.cdc.gov/hepatitis/hbv/bfaq.htm
198Nunes, E. V., Krupitsky, E., Ling, W., Zummo, J.,
Memisoglu, A., Silverman, B. L., & Gastfriend, D. R.
(2015). Treating opioid dependence with injectable
extended-release naltrexone (XR-NTX): Who will
respond? Journal of Addiction Medicine, 9(3), 238–243.
199Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
200Sigmon, S. C., Bisaga, A., Nunes, E. V., O’Connor, P. G.,
Kosten, T., & Woody, G. (2012). Opioid detoxifcation and
naltrexone induction strategies: Recommendations for
clinical practice. American Journal of Drug and Alcohol
Abuse, 38(3), 187–199.
201Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
202Comer, S. D., Mannelli, P., Alam, D., Douaihy, A., Nangia,
N., Akerman, S. C., ... Sullivan, M. A. (2020). Transition of
patients with opioid use disorder from buprenorphine to
extended-release naltrexone: A randomized clinical trial
assessing two transition regimens. American Journal on
Addictions, 29(4), 313–322.
3-118
Medications for Opioid Use Disorder TIP 63
203Sullivan, M. A., Bisaga, A., Mariani, J. J., Glass, A., Levin,
F. R., Comer, S. D., & Nunes, E. V. (2013). Naltrexone
treatment for opioid dependence: Does its effectiveness
depend on testing the blockade? Drug and Alcohol
Dependence, 133(1), 80–85.
204Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
205Kosten, T. R., Morgan, C., & Kleber, H. D. (1992). Phase
II clinical trials of buprenorphine: Detoxifcation and
induction onto naltrexone. NIDA Research Monograph,
121, 101–119.
206Bisaga, A., Sullivan, M. A., Glass, A., Mishlen, K.,
Pavlicova, M., Haney, M., … Nunes, E. V. (2015). The
effects of dronabinol during detoxifcation and the
initiation of treatment with extended release naltrexone.
Drug and Alcohol Dependence, 154, 38–45.
207Sigmon, S. C., Bisaga, A., Nunes, E. V., O’Connor, P. G.,
Kosten, T., & Woody, G. (2012). Opioid detoxifcation and
naltrexone induction strategies: Recommendations for
clinical practice. American Journal of Drug and Alcohol
Abuse, 38(3), 187–199.
208Sullivan, M., Bisaga, A., Pavlicova, M., Choi, C. J.,
Mishlen, K., Carpenter, K. M., … Nunes, E. V. (2017).
Long-acting injectable naltrexone induction: A
randomized trial of outpatient opioid detoxifcation with
naltrexone versus buprenorphine. American Journal of
Psychiatry, 174(5), 459–467.
209Sullivan, M., Bisaga, A., Pavlicova, M., Choi, C. J.,
Mishlen, K., Carpenter, K. M., … Nunes, E. V. (2017).
Long-acting injectable naltrexone induction: A
randomized trial of outpatient opioid detoxifcation with
naltrexone versus buprenorphine. American Journal of
Psychiatry, 174(5), 459–467.
210Bisaga, A. (2015). Implementing antagonist-based
relapse prevention treatment for buprenorphine-treated
individuals. Providence, RI: Providers’ Clinical Support
System for Medication-Assisted Treatment.
211Shearer, J., Wodak, A. D., & Dolan, K. A. (2007).
Evaluation of a prison-based naltrexone program.
International Journal of Prisoner Health, 3(3), 214–224.
212Adi, Y., Juarez-Garcia, A., Wang, D., Jowett, S., Frew, E.,
Day, E., … Burls, A. (2007). Oral naltrexone as a treatment
for relapse prevention in formerly opioid-dependent drug
users: A systematic review and economic evaluation.
Health Technology Assessment, 11(6), iii–iv, 1–85.
213Department of Veterans Affairs & Department of
Defense. (2015). VA/DoD clinical practice guideline for
the management of substance use disorders. Retrieved
October 16, 2017, from www.healthquality.va.gov
/guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf
214Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(2), 1–45.
215Ling, W., & Wesson, D. R. (1984). Naltrexone treatment
for addicted health-care professionals: A collaborative
private practice experience. Journal of Clinical Psychiatry,
45(9 Pt. 2), 46–48.
216Washton, A. M., Gold, M. S., & Pottash, A. C. (1984).
Successful use of naltrexone in addicted physicians and
business executives. Advances in Alcohol and Substance
Abuse, 4(2), 89–96.
217Sullivan, M. A., Rothenberg, J. L., Vosburg, S. K., Church,
S. H., Feldman, S. J., Epstein, E. M., … Nunes, E. V.
(2006). Predictors of retention in naltrexone maintenance
for opioid dependence: Analysis of a Stage I trial.
American Journal on Addictions, 15(2), 150–159.
218Sullivan, M. A., Garawi, F., Bisaga, A., Comer, S. D.,
Carpenter, K., Raby, W. N., … Nunes, E. V. (2007).
Management of relapse in naltrexone maintenance for
heroin dependence. Drug and Alcohol Dependence,
91(2–3), 289–292.
219Sullivan, M. A., Garawi, F., Bisaga, A., Comer, S. D.,
Carpenter, K., Raby, W. N., … Nunes, E. V. (2007).
Management of relapse in naltrexone maintenance for
heroin dependence. Drug and Alcohol Dependence,
91(2–3), 289–292.
220American Society of Addiction Medicine. (2017). Sample
treatment agreement. Retrieved October 19, 2017, from
www.asam.org/docs/default-source
/advocacy/sample-treatment-agreement30fa159472bc60
4ca5b7ff000030b21a.pdf?sfvrsn=0
221Alkermes. (2013). Patient counseling tool: VIVITROL
(naltrexone for extended-release injectable suspension.
Retrieved January 9, 2018, from www.vivitrolrems.com
/content/pdf/patinfo-counseling-tool.pdf
222Alkermes. (2015). Key techniques to reduce severe
injection site reactions: VIVITROL (naltrexone for
extended release injectable suspension) intramuscular
injection. Retrieved January 9, 2018, from www
.vivitrolrems.com/content/pdf/patinfo-injection
-poster.pdf
223Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
224Caldiero, R. M., Parran, T. J., Adelman, C. L., & Piche, B.
(2006). Inpatient initiation of buprenorphine maintenance
vs. detoxifcation: Can retention of opioid-dependent
patients in outpatient counseling be improved? American
Journal on Addictions, 15(1), 1–7.
3-119
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
225Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., … Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
226Fiellin, D. A., Moore, B. A., Sullivan, L. E., Becker, W.
C., Pantalon, M. V., Chawarski, M. C., … Schottenfeld,
R. S. (2008). Long-term treatment with buprenorphine/
naloxone in primary care: Results at 2–5 years. American
Journal on Addictions, 17(2), 116–120.
227Edelman, E. J., Chantarat, T., Caffrey, S., Chaudhry, A.,
O’Connor, P. G., Weiss, L., … Fiellin, L. E. (2014). The
impact of buprenorphine/naloxone treatment on HIV
risk behaviors among HIV-infected, opioid-dependent
patients. Drug and Alcohol Dependence, 139, 79–85.
228Sullivan, L. E., Moore, B. A., Chawarski, M. C., Pantalon,
M. V., Barry, D., O’Connor, P. G., … Fiellin, D. A. (2008).
Buprenorphine/naloxone treatment in primary care is
associated with decreased human immunodefciency virus
risk behaviors. Journal of Substance Abuse Treatment,
35(1), 87–92.
229Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède,
J. P., & Tignol, J. (2004). French feld experience with
buprenorphine. American Journal on Addictions,
13(Suppl. 1), S17–S28.
230Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
231Herget, G. (2005). Methadone and buprenorphine added
to the WHO list of essential medicines. HIV/AIDS Policy
and Law Review, 10(3), 23–24.
232Department of Veterans Affairs & Department of
Defense. (2015). VA/DoD clinical practice guideline for
the management of substance use disorders. Retrieved
October 16, 2017, from www.healthquality.va.gov/
guidelines/MH/sud/VADoDSUDCPGRevised22216.pdf
233Orexo US. (2016). Zubsolv (buprenorphine and naloxone)
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from
www.zubsolv.com/wp-content/uploads/2015/01
/ZubsolvFullPrescribingInformation.pdf
234BioDelivery Sciences International. (2018). Bunavail
(buprenorphine and naloxone buccal flm): Highlights
of prescribing information. Retrieved April 28, 2021,
from www.accessdata.fda.gov/drugsatfda_docs/
label/2018/205637s016lbl.pdf
235BioDelivery Sciences International. (2018). Bunavail
(buprenorphine and naloxone buccal flm): Highlights
of prescribing information. Retrieved April 28, 2021,
from www.accessdata.fda.gov/drugsatfda_docs/
label/2018/205637s016lbl.pdf
236Food and Drug Administration. (n.d.). Drugs@FDA: FDA
approved drug products. Retrieved October 16, 2017,
from www.accessdata.fda.gov/scripts/cder
/drugsatfda/index.cfm
237Roxane Laboratories. (2015). Buprenorphine and
naloxone sublingual tablets: Full prescribing information.
Retrieved October 16, 2017, from
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
?setid=713db2c6-0544-4633-b874-cfbeaf93db89
238Food and Drug Administration. (n.d.). Drugs@FDA: FDA
approved drug products. Retrieved October 16, 2017,
from www.accessdata.fda.gov/scripts/cder
/drugsatfda/index.cfm
239Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
240Food and Drug Administration. (n.d.). Drugs@FDA: FDA
approved drug products. Retrieved October 16, 2017,
from www.accessdata.fda.gov/scripts/cder
/drugsatfda/index.cfm
241Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
242Orexo US. (2015). Zubsolv (buprenorphine and naloxone)
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from
www.zubsolv.com/wp-content/uploads/2015/01
/ZubsolvFullPrescribingInformation.pdf
243Food and Drug Administration. (n.d.). Drugs@FDA: FDA
approved drug products. Retrieved October 16, 2017,
from www.accessdata.fda.gov/scripts/cder
/drugsatfda/index.cfm
244Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
245Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
246Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
3-120
Medications for Opioid Use Disorder TIP 63
247Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
248Amass, L., Kamien, J. B., & Mikulich, S. K. (2001).
Thrice-weekly supervised dosing with the combination
buprenorphine-naloxone tablet is preferred to daily
supervised dosing by opioid-dependent humans. Drug
and Alcohol Dependence, 61(2), 173–181.
249Schottenfeld, R. S., Pakes, J., O’Connor, P., Chawarski,
M., Oliveto, A., & Kosten, T. R. (2000). Thrice-weekly
versus daily buprenorphine maintenance. Biological
Psychiatry, 47(12), 1072–1079.
250Walsh, S. L., Preston, K. L., Stitzer, M. L., Cone, E.
J., & Bigelow, G. E. (1994). Clinical pharmacology of
buprenorphine: Ceiling effects at high doses. Clinical
Pharmacology and Therapeutics, 55(5), 569–580.
251Elkader, A., & Sproule, B. (2005). Buprenorphine: Clinical
pharmacokinetics in the treatment of opioid dependence.
Clinical Pharmacokinetics, 44(7), 661–680.
252Kuhlman, J. J., Jr., Levine, B., Johnson, R. E., Fudala,
P. J., & Cone, E. J. (1998). Relationship of plasma
buprenorphine and norbuprenorphine to withdrawal
symptoms during dose induction, maintenance and
withdrawal from sublingual buprenorphine. Addiction,
93(4), 549–559.
253Indivor. (2016). Label: Suboxone – buprenorphine
hydrochloride, naloxone hydrochloride flm, soluble.
Retrieved January 9, 2018, from https://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid
=8a5edcf9-828c-4f97-b671-268ab13a8ecd
254Marsch, L. A., Bickel, W. K., Badger, G. J., & Jacobs, E. A.
(2005). Buprenorphine treatment for opioid dependence:
The relative effcacy of daily, twice and thrice weekly
dosing. Drug & Alcohol Dependence, 77(2), 195–204.
255Jones, J. D., Sullivan, M. A., Vosburg, S. K., Manubay,
J. M., Mogali, S., Metz, V., & Comer, S. D. (2015).
Abuse potential of intranasal buprenorphine versus
buprenorphine/naloxone in buprenorphine-maintained
heroin users. Addiction Biology, 20(4), 784–798.
256Walsh, S. L., Nuzzo, P. A., Babalonis, S., Casselton, V.,
& Lofwall, M. R. (2016). Intranasal buprenorphine alone
and in combination with naloxone: Abuse liability and
reinforcing effcacy in physically dependent opioid
abusers. Drug and Alcohol Dependence, 162, 190–198.
257Indivior. (2017). Sublocade (buprenorphine extended-
release) injection: Full prescribing information. Retrieved
December 18, 2017, from www.accessdata
.fda.gov/drugsatfda_docs/label/2017/209819s000lbl
.pdf
258Elkader, A., & Sproule, B. (2005). Buprenorphine: Clinical
pharmacokinetics in the treatment of opioid dependence.
Clinical Pharmacokinetics, 44(7), 661–680.
259Zhang, W., Ramamoorthy, Y., Tyndale, R. F., & Sellers,
E. M. (2003). Interaction of buprenorphine and its
metabolite norbuprenorphine with cytochromes p450 in
vitro. Drug Metabolism and Disposition: The Biological
Fate of Chemicals, 31(6), 768–772.
260McCance-Katz, E. F., Sullivan, L. E., & Nallani, S. (2010).
Drug interactions of clinical importance among the
opioids, methadone and buprenorphine, and other
frequently prescribed medications: A review. American
Journal on Addictions, 19(1), 4–16.
261Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
262Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
263Selden, T., Ahlner, J., Druid, H., & Kronstrand, R. (2012).
Toxicological and pathological fndings in a series of
buprenorphine related deaths. Possible risk factors for
fatal outcome. Forensic Science International, 220(1–3),
284–290.
264Hakkinen, M., Launiainen, T., Vuori, E., & Ojanpera, I.
(2012). Benzodiazepines and alcohol are associated with
cases of fatal buprenorphine poisoning. European Journal
of Clinical Pharmacology, 68(3), 301–309.
265Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
266Toce, M. S., Burns, M. M., & O’Donnell, K. A. (2017).
Clinical effects of unintentional pediatric buprenorphine
exposures: Experience at a single tertiary care center.
Clinical Toxicology (Philadelphia, Pa.), 55(1), 12–17.
267Saxon, A. J., Ling, W., Hillhouse, M., Thomas, C., Hasson,
A., Ang, A., … Jacobs, P. (2013). Buprenorphine/
naloxone and methadone effects on laboratory indices
of liver health: A randomized trial. Drug and Alcohol
Dependence, 128(1–2), 71–76.
268Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
269Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
3-121
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
270Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
271Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
272Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
273Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
274Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
275Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
276Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
277Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
278Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
279Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
280Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed
.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
281Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetic, 54(8), 837–849.
282Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
283Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
284Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
285Indivior. (2016). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
286Indivior. (2016). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
287Strain, E. C., & Lofwall, M. R. (Eds.). (2008).
Buprenorphine. The American Psychiatric Publishing
textbook of substance abuse treatment (4th ed.).
Arlington, VA: American Psychiatric Publishing.
288Walsh, S. L., June, H. L., Schuh, K. J., Preston, K.
L., Bigelow, G. E., & Stitzer, M. L. (1995). Effects of
buprenorphine and methadone in methadone-maintained
subjects. Psychopharmacology, 119(3), 268–276.
289Strain, E. C., Preston, K. L., Liebson, I. A., & Bigelow, G. E.
(1995). Buprenorphine effects in methadone-maintained
volunteers: Effects at two hours after methadone. Journal
of Pharmacology and Experimental Therapeutics, 272(2),
628–638.
290Rosado, J., Walsh, S. L., Bigelow, G. E., & Strain, E. C.
(2007). Sublingual buprenorphine/naloxone precipitated
withdrawal in subjects maintained on 100mg of daily
methadone. Drug and Alcohol Dependence, 90(2–3),
261–269.
291Walsh, S. L., June, H. L., Schuh, K. J., Preston, K.
L., Bigelow, G. E., & Stitzer, M. L. (1995). Effects of
buprenorphine and methadone in methadone-maintained
subjects. Psychopharmacology, 119(3), 268–276.
292Jones, H. E., Dengler, E., Garrison, A., O’Grady, K.
E., Seashore, C., Horton, E., … Thorp, J. (2014).
Neonatal outcomes and their relationship to maternal
buprenorphine dose during pregnancy. Drug and Alcohol
Dependence, 134, 414–417.
293Cleary, B. J., Reynolds, K., Eogan, M., O’Connell, M.
P., Fahey, T., Gallagher, P. J., … Murphy, D. J. (2014).
Methadone dosing and prescribed medication use in
a prospective cohort of opioid-dependent pregnant
women. Addiction, 108(4), 762–770.
3-122
Medications for Opioid Use Disorder TIP 63
294Kaltenbach, K., Holbrook, A. M., Coyle, M. G., Heil, S.
H., Salisbury, A. L. Stine, S. M., … Jones, H. E. (2012).
Predicting treatment for neonatal abstinence syndrome
in infants born to women maintained on opioid agonist
medication. Addiction, 107(Suppl. 1), 45–52.
295McCance-Katz, E. F., Sullivan, L. E., & Nallani, S. (2010).
Drug interactions of clinical importance among the
opioids, methadone and buprenorphine, and other
frequently prescribed medications: A review. American
Journal on Addictions, 19(1), 4–16.
296Center for Substance Abuse Treatment. (2004). Clinical
guidelines for the use of buprenorphine in the treatment
of opioid addiction. Treatment Improvement Protocol
(TIP) Series 40. HHS Publication No. (SMA) 04-3939.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
297Indivior. (2016). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
298McCance-Katz, E. F., Moody, D. E., Morse, G. D., Ma, Q.,
DiFrancesco, R., Friedland, G., … Rainey, P. M. (2007).
Interaction between buprenorphine and atazanavir or
atazanavir/ritonavir. Drug and Alcohol Dependence,
91(2–3), 269–278.
299Bruce, R. D., & Altice, F. L. (2006). Three case reports of a
clinical pharmacokinetic interaction with buprenorphine
and atazanavir plus ritonavir. AIDS, 20(5), 783–784.
300Vergara-Rodriguez, P., Tozzi, M. J., Botsko, M., Nandi,
V., Altice, F., Egan, J. E., … Fiellin, D. A. (2011).
Hepatic safety and lack of antiretroviral interactions
with buprenorphine/naloxone in HIV-infected opioid-
dependent patients. Journal of Acquired Immune
Defciency Syndromes, 56(Suppl. 1), S62–S67.
301McCance-Katz, E. F., Moody, D. E., Prathikanti, S.,
Friedland, G., & Rainey, P. M. (2011). Rifampin, but
not rifabutin, may produce opiate withdrawal in
buprenorphine-maintained patients. Drug and Alcohol
Dependence, 118(2–3), 326–334.
302Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information.
Retrieved October 16, 2017, from https://
dailymed.nlm.nih.gov/dailymed/drugInfo.
cfm?setid=1bf8b35a-b769-465c-a2f8-099868dfcd2f
303McCance-Katz, E. F., Moody, D. E., Morse, G. D., Ma, Q.,
DiFrancesco, R., Friedland, G., … Rainey, P. M. (2007).
Interaction between buprenorphine and atazanavir or
atazanavir/ritonavir. Drug and Alcohol Dependence,
91(2–3), 269–278.
304McCance-Katz, E. F., Moody, D. E., Morse, G. D., Ma, Q.,
DiFrancesco, R., Friedland, G., … Rainey, P. M. (2007).
Interaction between buprenorphine and atazanavir or
atazanavir/ritonavir. Drug and Alcohol Dependence,
91(2–3), 269–278.
305Bruce, R. D., Moody, D. E., Altice, F. L., Gourevitch, M. N.,
& Friedland, G. H. (2013). A review of pharmacological
interactions between HIV or hepatitis C virus
medications and opioid agonist therapy: Implications
and management for clinical practice. Expert Review of
Clinical Pharmacology, 6(3), 249–269.
306Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information.
Retrieved October 16, 2017, from https://
dailymed.nlm.nih.gov/dailymed/drugInfo.
cfm?setid=1bf8b35a-b769-465c-a2f8-099868dfcd2f
307Bruce, R. D., Moody, D. E., Altice, F. L., Gourevitch, M. N.,
& Friedland, G. H. (2013). A review of pharmacological
interactions between HIV or hepatitis C virus
medications and opioid agonist therapy: Implications
and management for clinical practice. Expert Review of
Clinical Pharmacology, 6(3), 249–269.
308Gruber, V. A., Rainey, P. M., Moody, D. E., Morse, G. D.,
Ma, Q., Prathikanti, S., … McCance-Katz, E. F. (2012).
Interactions between buprenorphine and the protease
inhibitors darunavir-ritonavir and fosamprenavir-ritonavir.
Clinical Infectious Diseases, 54(3), 414–423.
309Bruce, R. D., Moody, D. E., Altice, F. L., Gourevitch, M. N.,
& Friedland, G. H. (2013). A review of pharmacological
interactions between HIV or hepatitis C virus
medications and opioid agonist therapy: Implications
and management for clinical practice. Expert Review of
Clinical Pharmacology, 6(3), 249–269.
310McCance-Katz, E. F., Moody, D. E., Morse, G. D.,
Friedland, G., Pade, P., Baker, J., … Rainey, P. M. (2006).
Interactions between buprenorphine and antiretrovirals.
I. The nonnucleoside reverse-transcriptase inhibitors
efavirenz and delavirdine. Clinical Infectious Diseases,
43(Suppl. 4), S224–S234.
311McCance-Katz, E. F., Moody, D. E., Morse, G. D.,
Friedland, G., Pade, P., Baker, J., … Rainey, P. M. (2006).
Interactions between buprenorphine and antiretrovirals.
I. The nonnucleoside reverse-transcriptase inhibitors
efavirenz and delavirdine. Clinical Infectious Diseases,
43(Suppl. 4), S224–S234.
312Bruce, R. D., Winkle, P., Custodio, J., Yin, X., Rhee, M.,
Andrews, J., … Ramanathan, S. (2012, September).
Pharmacokinetics of cobicistat-boosted elvitegravir
administered in combination with methadone or
buprenorphine/naloxone. Paper presented at the 52nd
Interscience Conference on Antimicrobial Agents and
Chemotherapy, San Francisco, CA.
313McCance-Katz, E. F., Moody, D. E., Morse, G. D., Ma, Q.,
& Rainey, P. M. (2010). Lack of clinically signifcant drug
interactions between nevirapine and buprenorphine.
American Journal on Addictions, 19(1), 30–37.
3-123
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
314McCance-Katz, E. F., Moody, D. E., Smith, P. F., Morse,
G. D., Friedland, G., Pade, P., … Rainey, P. (2006).
Interactions between buprenorphine and antiretrovirals.
II. The protease inhibitors nelfnavir, lopinavir/ritonavir,
and ritonavir. Clinical Infectious Diseases, 43(Suppl. 4),
S235–S246.
315Bruce, R. D., Altice, F. L., Moody, D. E., Lin, S. N.,
Fang, W. B., Sabo, J. P., … Friedland, G. H. (2009).
Pharmacokinetic interactions between buprenorphine/
naloxone and tipranavir/ritonavir in HIV-negative subjects
chronically receiving buprenorphine/naloxone. Drug and
Alcohol Dependence, 105(3), 234–239.
316Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
317Isenberg, D., Wong, S. C., & Curtis, J. A. (2008).
Serotonin syndrome triggered by a single dose of
Suboxone. American Journal of Emergency Medicine,
26(7), 840.e3–840.e5.
318Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
319Soyka, M. (2013). Buprenorphine use in pregnant opioid
users: A critical review. CNS Drugs, 27(8), 653–662.
320Saxon, A. J., Ling, W., Hillhouse, M., Thomas, C., Hasson,
A., Ang, A., … Jacobs, P. (2013). Buprenorphine/
naloxone and methadone effects on laboratory indices
of liver health: A randomized trial. Drug and Alcohol
Dependence, 128(1–2), 71–76.
321Vergara-Rodriguez, P., Tozzi, M. J., Botsko, M., Nandi,
V., Altice, F., Egan, J. E., … Fiellin, D. A. (2011).
Hepatic safety and lack of antiretroviral interactions
with buprenorphine/naloxone in HIV-infected opioid-
dependent patients. Journal of Acquired Immune
Defciency Syndromes, 56(Suppl. 1), S62–S67.
322U.S. Preventive Services Task Force. (2019).
Final Recommendation Statement on Human
Immunodefciency Virus (HIV) Infection:
Screening. Retrieved January 11, 2020, from
www.uspreventiveservicestaskforce.org/Page/
Document/RecommendationStatementFinal/
human-immunodefciency-virus-hiv-infection-screening
323Centers for Disease Control and Prevention. Testing
Recommendations for Hepatitis C Virus Infection.
October 15, 2015. Retrieved January 11, 2020, from
www.cdc.gov/hepatitis/hcv/guidelinesc.htm
324Centers for Disease Control and Prevention. (2016). Viral
hepatitis. Retrieved October 16, 2017, from
www.cdc.gov/hepatitis/hbv/bfaq.htm
325Lofwall, M. R., & Havens, J. R. (2012). Inability to access
buprenorphine treatment as a risk factor for using
diverted buprenorphine. Drug and Alcohol Dependence,
126(3), 379–383.
326Bazazi, A. R., Yokell, M., Fu, J. J., Rich, J. D., & Zaller, N.
D. (2011). Illicit use of buprenorphine/naloxone among
injecting and noninjecting opioid users. Journal of
Addiction Medicine, 5(3), 175–180.
327Moratti, E., Kashanpour, H., Lombardelli, T., & Maisto,
M. (2010). Intravenous misuse of buprenorphine:
Characteristics and extent among patients undergoing
drug maintenance therapy. Clinical Drug Investigation,
30(Suppl. 1), 3–11.
328Braeburn Pharmaceuticals. (2016). Probuphine
(buprenorphine) implant: Full prescribing information.
Retrieved October 16, 2017, from www.accessdata.fda
.gov/drugsatfda_docs/label/2016/204442Orig1s000lbl
.pdf
329Braeburn Pharmaceuticals. (2016). Probuphine
(buprenorphine) implant: Full prescribing information.
Retrieved October 16, 2017, from www.accessdata.fda
.gov/drugsatfda_docs/label/2016/204442Orig1s000lbl
.pdf
330Center for Substance Abuse Treatment. (2004). Clinical
guidelines for the use of buprenorphine in the treatment
of opioid addiction. Treatment Improvement Protocol
(TIP) Series 40. HHS Publication No. (SMA) 04-3939.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
331Walley, A. Y., Alperen, J. K., Cheng, D. M., Botticelli, M.,
Castro-Donlan, C., Samet, J. H., & Alford, D. P. (2008).
Offce-based management of opioid dependence with
buprenorphine: Clinical practices and barriers. Journal of
General Internal Medicine, 23(9), 1393–1398.
332Gunderson, E. W., Wang, X. Q., Fiellin, D. A., Bryan, B.,
& Levin, F. R. (2010). Unobserved versus observed offce
buprenorphine/naloxone induction: A pilot randomized
clinical trial. Addictive Behaviors, 35(5), 537–540.
333Lee, J. D., Vocci, F., & Fiellin, D. A. (2014). Unobserved
“home” induction onto buprenorphine. Journal of
Addiction Medicine, 8(5), 299–308.
334American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
335Providers Clinical Support System for Medication
Assisted Treatment. (2013, November). PCSS Guidance.
Retrieved December 18, 2017, from http://pcssmat.org/
wp-content/uploads/2014/02/PCSS-MAT
GuidanceBuprenorphineInduction.Casadonte.pdf
336Tompkins, D. A., & Strain, E. C. (2011). Buprenorphine
in the treatment of opioid dependence. In P. Ruiz & E.
C. Strain (Eds.), Substance abuse. A comprehensive
textbook (5th ed., pp. 437–446). Philadelphia, PA:
Wolters Kluwer.
3-124
Medications for Opioid Use Disorder TIP 63
337Indivior. (2016). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
338Strain, E. C. (2006). Clinical use of buprenorphine. In E.
C. Strain & M. L. Stitzer (Eds.) The treatment of opioid
dependence (pp. 230–252). Baltimore, MD: Johns
Hopkins University Press.
339Rich, J. D., McKenzie, M., Dickman, S., Bratberg, J.,
Lee, J. D., & Schwartz, R. P. (2011). An adverse reaction
to buprenorphine/naloxone induction in prison: A case
report. Addictive Disorders and Their Treatment, 10(4),
199–200.
340Vocci, F. J., Schwartz, R. P., Wilson, M. E., Gordon, M.
S., Kinlock, T. W., Fitzgerald, T. T., … Jaffe, J. H. (2015).
Buprenorphine dose induction in non-opioid-tolerant
pre-release prisoners. Drug and Alcohol Dependence,
156, 133–138.
341Tompkins, D. A., & Strain, E. C. (2011). Buprenorphine
in the treatment of opioid dependence. In P. Ruiz & E.
C. Strain (Eds.), Substance abuse: A comprehensive
textbook (5th ed., pp. 437–446). Philadelphia, PA:
Wolters Kluwer.
342Rosado, J., Walsh, S. L., Bigelow, G. E., & Strain, E. C.
(2007). Sublingual buprenorphine/naloxone precipitated
withdrawal in subjects maintained on 100mg of daily
methadone. Drug and Alcohol Dependence, 90(2–3),
261–269.
343Zubieta, J., Greenwald, M. K., Lombardi, U., Woods, J.
H., Kilbourn, M. R., Jewett, D. M., … Johanson, C. E.
(2000). Buprenorphine-induced changes in mu-opioid
receptor availability in male heroin-dependent volunteers:
A preliminary study. Neuropsychopharmacology, 23(3),
326–334.
344Hser, Y., Saxon, A. J., Huang, D., Hasson, A., Thomas,
C., Hillhouse, M. … Ling, W. (2014). Treatment retention
among patients randomized to buprenorphine/naloxone
compared to methadone in a multi-site trial. Addiction,
109(1), 79–87.
345American College of Obstetricians and Gynecologists
Committee Opinion. (2017, August). Opioid use and
opioid use disorder in pregnancy. Number 711.
346Debelak, K., Morrone, W. R., O’Grady, K. E., & Jones, H.
E. (2013). Buprenorphine + naloxone in the treatment of
opioid dependence during pregnancy-initial patient care
and outcome data. American Journal on Addictions, 22,
252–254.
347Wiegand, S. L., Stringer, E. M., Stuebe, A. M., Jones,
H., Seashore, C., & Thorp, J. (2015). Buprenorphine
and naloxone compared with methadone treatment in
pregnancy. Obstetrics & Gynecology, 125, 363–368.
348American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
349Substance Abuse and Mental Health Services
Administration. (2018). Clinical guidance for treating
pregnant and parenting women with opioid use disorder
and their infants. HHS Publication No. (SMA) 18-5054.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
350Chavoustie, S., Frost, M., Snyder, O., Owen, J., Darwish,
M., Dammerman, R., & Sanjurjo, V. (2017). Buprenorphine
implants in medical treatment of opioid addiction. Expert
Review of Clinical Pharmacology, 10(8), 799–807.
351Hser, Y. I., Huang, D., Saxon, A. J., Woody, G., Moskowitz,
A. L., Matthews, A. G., & Ling, W. (2017). Distinctive
trajectories of opioid use over an extended follow-up of
patients in a multisite trial on buprenorphine + naloxone
and methadone. Journal of Addiction Medicine, 11(1),
63–69.
352Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter,
J., Thomas, C., … Bilangi, R. (2009). Buprenorphine
tapering schedule and illicit opioid use. Addiction, 104(2),
256–265.
353Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
354American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
355Henry-Edwards, S., Gowing, L., White, J., Ali, R., Bell, J.,
Brough, R., … Quigley, A. (2003). Clinical guidelines and
procedures for the use of methadone in the maintenance
treatment of opioid dependence. Publication approval
number: 3263 (JN 7616).
356World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment of
opioid dependence. Geneva, Switzerland: WHO Press.
357Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter,
J., Thomas, C., … Bilangi, R. (2009). Buprenorphine
tapering schedule and illicit opioid use. Addiction, 104(2),
256–265.
358Food and Drug Administration. (2017, May). Appropriate
use checklist: Buprenorphine-containing transmucosal
products for opioid dependence. Silver Spring, MD:
Author.
359American Society of Addiction Medicine. (2017). Sample
treatment agreement. Retrieved October 19, 2017, from
www.asam.org/docs/default-source
/advocacy/sample-treatment-agreement30fa
159472bc604ca5b7ff000030b21a.pdf?sfvrsn=0
3-125
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
360Food and Drug Administration. (2017). FDA Drug Safety
Communication: FDA urges caution about withholding
opioid addiction medications from patients taking
benzodiazepines or CNS depressants: Careful medication
management can reduce risks. Retrieved December 18,
2017, from www.fda.gov/Drugs/Drug
Safety/ucm575307.htm
361Lintzeris, N., & Nielsen, S. (2010). Benzodiazepines,
methadone and buprenorphine: Interactions and clinical
management. American Journal on Addictions, 19(1),
59–72.
362Lintzeris, N., & Nielsen, S. (2010). Benzodiazepines,
methadone and buprenorphine: Interactions and clinical
management. American Journal on Addictions, 19(1),
59–72.
363Liebschutz, J. M., Crooks, D., Herman, D., Anderson,
B., Tsui, J., Meshesha, L. Z., … Stein, M. (2014).
Buprenorphine treatment for hospitalized, opioid-
dependent patients: A randomized clinical trial. JAMA
Internal Medicine, 174(8), 1369–1376.
364Weiss, L., Netherland, J., Egan, J. E., Flanigan, T. P.,
Fiellin, D. A., Finkelstein, R., & Altice, F. L. (2011).
Integration of buprenorphine/naloxone treatment into
HIV clinical care: Lessons from the BHIVES collaborative.
Journal of Acquired Immune Defciency Syndromes,
56(Suppl. 1), S68–S75.
365Weiss, R. D., Potter, J. S., Griffn, M. L., Provost, S. E.,
Fitzmaurice, G. M., McDermott, K. A., … Carroll, K. M.
(2015). Long-term outcomes from the National Drug
Abuse Treatment Clinical Trials Network Prescription
Opioid Addiction Treatment Study. Drug and Alcohol
Dependence, 150, 112–119.
366Substance Abuse and Mental Health Services
Administration. (2005). Substance abuse treatment
for persons with cooccurring disorders. Treatment
Improvement Protocol (TIP) Series 42. HHS Publication
No. (SMA) 133992. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
367Center for Substance Abuse Treatment. (2004). Clinical
guidelines for the use of buprenorphine in the treatment
of opioid addiction. Treatment Improvement Protocol
(TIP) Series 40. HHS Publication No. (SMA) 04-3939.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
368Drug Addiction Treatment Act of 2000, H. R. 2634
(1999–2000).
369Vujanovic, A. A., Bonn-Miller, M. O., & Petry, N. M.
(2016). Co-occurring posttraumatic stress and substance
use: Emerging research on correlates, mechanisms, and
treatments—Introduction to the special issue. Psychology
of Addictive Behaviors, 30(7), 713–719.
370Stitzer, M. L., & Vandrey, R. (2008). Contingency
management: Utility in the treatment of drug abuse
disorders. Clinical Pharmacology and Therapeutics, 83(4),
644–647.
371Donovan, D. M., Ingalsbe, M. H., Benbow, J., & Daley,
D. C. (2013). 12-step interventions and mutual support
programs for substance use disorders: An overview.
Social Work in Public Health, 28(3–4), 313–332.
372Donovan, D. M., Ingalsbe, M. H., Benbow, J., & Daley,
D. C. (2013). 12-step interventions and mutual support
programs for substance use disorders: An overview.
Social Work in Public Health, 28(3–4), 313–332.
373McLellan, A. T., & White, W. (2012). Opioid maintenance
and recovery-oriented systems of care: It is time to
integrate (p. 2). London, England: National Treatment
Agency for Substance Misuse.
374American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
375Substance Abuse and Mental Health Services
Administration. (2012). Clinical drug testing in primary
care. Technical Assistance Publication (TAP) Series
32. HHS Publication No. (SMA) 12-4668. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
376Jarvis, M., Williams, J., Hurford, M., Lindsay, D., Lincoln,
P., Giles, L., … Safarian, T. (2017). Appropriate use of
drug testing in clinical addiction medicine. Journal of
Addiction Medicine, 11(3), 163–173.
377Stoller, K. B., Stephens, M. A. C., & Schorr, A. (2016).
Integrated service delivery models for opioid treatment
programs in an era of increasing opioid addiction, health
reform, and parity. Retrieved May 21, 2017, from www.
aatod.org/wp-content/uploads/2016/07/2nd
-Whitepaper-.pdf
378Rich, J. D., McKenzie, M., Larney, S., Wong, J. B., Tran,
L., Clarke, J., … Zaller, N. (2015, July 25). Methadone
continuation versus forced withdrawal on incarceration in
a combined US prison and jail: A randomised, open-label
trial. Lancet, 386(9991), 350–359.
379Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
380Genberg, B. L., Gillespie, M., Schuster, C. R., Johanson,
C.-E., Astemborski, J., Kirk, G. D., … Mehta, S. H.
(2013). Prevalence and correlates of street-obtained
buprenorphine use among current and former injectors
in Baltimore, Maryland. Addictive Behaviors, 38(12),
2868–2873.
381Genberg, B. L., Gillespie, M., Schuster, C. R., Johanson,
C.-E., Astemborski, J., Kirk, G. D., … Mehta, S. H.
(2013). Prevalence and correlates of street-obtained
buprenorphine use among current and former injectors
in Baltimore, Maryland. Addictive Behaviors, 38(12),
2868–2873.
3-126
Medications for Opioid Use Disorder TIP 63
382Cicero, T. J., Ellis, M. S., Surratt, H. L., & Kurtz, S. P.
(2014). Factors contributing to the rise of buprenorphine
misuse: 2008-2013. Drug and Alcohol Dependence, 142,
98–104.
383Lofwall, M. R., & Walsh, S. L. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world.
Journal of Addiction Medicine, 8(5), 315–326.
384United States National Library of Medicine. (2017,
October). Buprenorphine sublingual and buccal (opioid
dependence). Retrieved December 18, 2017, from
https://medlineplus.gov/druginfo/meds/a605002.html
385American Society of Addiction Medicine. (2016). Sample
offce-based opioid use disorder policy and procedure
manual. Retrieved October 19, 2017, from www.asam.
org/docs/default-source/advocacy/sample
-diversion-policy.pdf?sfvrsn=0
386Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
387Medication Assisted Treatment for Opioid Use Disorders.
HHS Final Rule, Fed. Reg. 81 44711 (July 8, 2016) (to be
codifed at 42 CFR pt. 8).
388Physical security controls for practitioners, 21 CFR §
1301.75 (2016).
389American Society of Addiction Medicine. (2016). Sample
offce-based opioid use disorder policy and procedure
manual. Retrieved October 19, 2017, from www.asam.
org/docs/default-source/advocacy/sample
-diversion-policy.pdf?sfvrsn=0
390Records for manufacturers, distributors, dispensers,
researchers, importers, exporters, registrants that reverse
distribute, and collectors, 21 CFR § 1304.22 (2014).
391Lofwall, M., & Walsh, S. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world (p.
316). Journal of Addiction Medicine, 8(5), 315–326.
392American Society of Addiction Medicine. (2016). Sample
offce-based opioid use disorder policy and procedure
manual. Retrieved October 19, 2017, from www.asam.
org/docs/default-source/advocacy/sample
-diversion-policy.pdf?sfvrsn=0
393Velez, C. M., Nicolaidis, C., Korthuis, P. T., & Englander,
H. (2016). “It’s been an experience, a life learning
experience”: A qualitative study of hospitalized patients
with substance use disorders. Journal of General Internal
Medicine, 32(3), 296–303.
394Liebschutz, J. M., Crooks, D., Herman, D., Anderson,
B., Tsui, J., Meshesha, L. Z., … Stein, M. (2014).
Buprenorphine treatment for hospitalized, opioid-
dependent patients: A randomized clinical trial. JAMA
Internal Medicine, 174(8), 1369–1376.
395D’Onofrio, G., O’Connor, P. G., Pantalon, M. V.,
Chawarski, M. C., Busch, S. H., Owens, P. H., …
Fiellin, D. A. (2015). Emergency department-initiated
buprenorphine/naloxone treatment for opioid
dependence: A randomized clinical trial. JAMA, 313(16),
1636–1644.
396Naeger, S., Ali, M. M., Mutter, R., Mark, T., & Hughey,
L. (2016). Post-discharge prescription flls following
an opioid hospitalization. Psychiatric Services, 67(11),
1264–1267.
397Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A.,
Bailey, M. K., & O’Malley, L. (2017, January). Opioid-
related inpatient stays and emergency department visits
by state, 2009–2014. HCUP Statistical Brief No. 219.
Rockville, MD: Agency for Healthcare Research and
Quality.
398Agency for Healthcare Research and Quality (2019).
Rate of Opioid-Related Inpatient Stays per 100,000
Population. Retrieved January 11, 2020, from www.
hcup-us.ahrq.gov/faststats/OpioidUseMap?setting=IP
399Administering or dispensing of narcotic drugs, 21 CFR §
1306.07 (2005).
400Alford, D., Compton, P., & Samet, H. (2006). Acute
pain management for patients receiving maintenance
methadone or buprenorphine therapy. Annals of Internal
Medicine, 144(2), 127–134.
401Sen, S., Arulkumar, S., Cornett, E. M., Gayle, J. A.,
Flower, R. R., Fox, C. J., & Kaye, A. D. (2016). New
pain management options for the surgical patient
on methadone and buprenorphine. Current Pain and
Headache Reports, 20(3), 16.
402Jones, H. E., Deppen, K., Hudak, M. L., Leffert, L.,
McClelland, C., Sahin, L., … Creanga, A. A. (2014).
Clinical care for opioid-using pregnant and postpartum
women: The role of obstetric providers. American Journal
of Obstetrics and Gynecology, 210(4), 302–310.
403Alizadeh, S., Mahmoudi, G. A., Solhi, H., Sadeghi-Sedeh,
B., Behzadi, R., & Kazemifar, A. M. (2015). Post-operative
analgesia in opioid dependent patients: Comparison of
intravenous morphine and sublingual buprenorphine.
Addiction and Health, 7(1–2), 60–65.
404Sen, S., Arulkumar, S., Cornett, E. M., Gayle, J. A.,
Flower, R. R., Fox, C. J., & Kaye, A. D. (2016). New
pain management options for the surgical patient
on methadone and buprenorphine. Current Pain and
Headache Reports, 20(3),16.
405Administering or dispensing of narcotic drugs, 21 CFR §
1306.07 (2005).
406Alford, D. P., Compton, P., & Samet, J. H. (2006). Acute
pain management for patients receiving maintenance
methadone or buprenorphine therapy. Annals of Internal
Medicine, 144(2), 127–134.
3-127
TIP 63Part 3 of 5—Medications for Opioid Use Disorder
407Devin, C. J., & McGirt, M. J. (2015). Best evidence in
multimodal pain management in spine surgery and means
of assessing postoperative pain and functional outcomes.
Journal of Clinical Neuroscience, 22(6), 930–938.
408Noska, A., Mohan, A., Wakeman, S., Rich, J., & Boutwell,
A. (2015). Managing opioid use disorder during and after
acute hospitalization: A case-based review clarifying
methadone regulation for acute care settings. Journal
of Addictive Behaviors, Therapy and Rehabilitation, 4(2),
1000138.
409Liebschutz, J. M., Crooks, D., Herman, D., Anderson,
B., Tsui, J., Meshesha, L. Z., … Stein, M. (2014).
Buprenorphine treatment for hospitalized, opioid-
dependent patients: A randomized clinical trial. JAMA
Internal Medicine, 174(8), 1369–1376.
410D’Onofrio, G., O’Connor, P. G., Pantalon, M. V.,
Chawarski, M. C., Busch, S. H., Owens, P. H., …
Fiellin, D. A. (2015). Emergency department-initiated
buprenorphine/naloxone treatment for opioid
dependence: A randomized clinical trial. JAMA, 313(16),
1636–1644.
411Substance Abuse and Mental Health Services
Administration. (2016, March). Special circumstances for
providing buprenorphine. Retrieved December 18, 2017,
from www.samhsa.gov/medication-assisted
-treatment/legislation-regulations-guidelines/special
-circumstances-providing-buprenorphine
412D’Onofrio, G., O’Connor, P. G., Pantalon, M. V.,
Chawarski, M. C., Busch, S. H., Owens, P. H., …
Fiellin, D. A. (2015). Emergency department-initiated
buprenorphine/naloxone treatment for opioid
dependence: A randomized clinical trial. JAMA, 313(16),
1636–1644.
413Huxtable, C. A., Roberts, L. J., Somogyi, A. A., &
Macintyre, P. E. (2011). Acute pain management
in opioid-tolerant patients: A growing challenge.
Anaesthesia and Intensive Care, 39(5), 804–823.
This page intentionally left blank.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Part 4: Bringing Together Addiction Treatment Counselors, Clients,
and Healthcare Professionals
For Healthcare and Addiction Professionals
Part 4 of this Treatment Improvement Protocol (TIP) is for addiction treatment professionals
and peer recovery support specialists who work with individuals who take a Food and Drug
Administration (FDA)-approved medication to treat opioid use disorder (OUD).
TIP Navigation
Executive Summary
For healthcare and addiction professionals,
policymakers, patients, and families
Part 1: Introduction to Medications for Opioid
Use Disorder Treatment
For healthcare and addiction professionals,
policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction
Treatment Counselors, Clients,
and Healthcare Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications for
Opioid Use Disorder
For healthcare and addiction professionals,
policymakers, patients, and families
KEY MESSAGES
• Many patients taking OUD medication
beneft from counseling as part of their
treatment.
• Counselors play the same role for clients
with OUD who take medication as for
clients with any other SUD.
• Counselors help clients recover
by addressing the challenges and
consequences of addiction.
• OUD is often a chronic illness requiring
ongoing communication among patients
and providers to ensure that patients
fully beneft from both medication and
psychosocial treatment and support.
• OUD medications are safe and effective
when prescribed and taken appropriately.
• Medication is integral to recovery for
many people with OUD. Medication
usually produces better treatment
outcomes than outpatient treatment
without medication.
• Supportive counseling environments
for clients who take OUD medication
can promote treatment and help build
recovery capital.
4-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 4 of 5
Contents
Overview and Context 4-1
Scope of the Problem 4-1
Setting the Stage 4-4
Distinguishing OUD From Physical Dependence on Opioid Medications 4-4
Understanding the Benefts of Medication for OUD 4-5
Reviewing the Evidence on Counseling in Support of Medication To Treat OUD 4-6
Using a Recovery-Oriented Approach to Treating Patients With OUD 4-8
Quick Guide to Medications 4-12
Understanding the Neurobiology of OUD 4-12
Learning How OUD Medications Work 4-12
Knowing What Prescribers Do 4-16
Counselor–Prescriber Communications 4-18
Obtaining Consent 4-18
Structuring Communications With Prescribers 4-19
Helping Clients Overcome Challenges in Accessing Resources 4-19
Creation of a Supportive Counseling Experience 4-20
Maintaining the Therapeutic Alliance 4-20
Educating Patients About OUD and a Chronic Care Approach to Its Treatment 4-21
Counseling Patients on Overdose Prevention and Treatment 4-21
Helping Patients Cope With Bias and Discrimination 4-22
Helping Patients Advocate for Themselves 4-26
Addressing Discrimination Against Clients Who Take OUD Medication 4-26
Helping Clients Find Accepting Mutual-Help Groups 4-30
Facilitating Groups That Include Patients Taking OUD Medication 4-33
Other Common Counseling Concerns 4-34
Notes 4-37
4-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
PART 4 of 5
Bringing Together Addiction Treatment
Counselors, Clients, and Healthcare Professionals
Part 4 of this TIP is for addiction treatment professionals and peer recovery support specialists
who work with individuals who take an FDA-approved medication for OUD—methadone,
naltrexone, or buprenorphine. These providers have direct helping relationships with clients.
They don’t prescribe or administer OUD medications, but they interact with healthcare profes-
sionals who do. They also help people who take OUD medication access supportive services
(e.g., transportation, child care, housing).
Overview and Context
Scope of the Problem
Opioid misuse has caused a growing nationwide
epidemic of OUD and unintentional overdose
deaths.1 This epidemic affects people in all
regions, of all ages, and from all walks of life.
Opioid misuse devastates families, burdens
emergency departments and frst responders,
fuels increases in hospital admissions, and strains
criminal justice and child welfare systems.
Counselors can play an integral role in
addressing this crisis. Counseling helps people
with OUD and other substance use disorders
(SUDs) change how they think, cope, react, and
acquire the skills and confdence necessary for
recovery. Counseling can provide support for
people who take medication to treat their OUD.
Patients may get counseling from prescribers or
other staff members in the prescribers’ practices
or by referral to counselors at specialty addiction
treatment programs or in private practice.
Counselors and peer recovery support specialists
can work with patients who take OUD med-
ication and refer patients with active OUD to
healthcare professionals for an assessment for
treatment with medication.
1.6MILLION
,
,
,
people in the U.S.
ages 12 and older
had OUD involving
PRESCRIPTION
OPIOIDS, HEROIN
or both in 2019.2
Part 4 uses “counselor” to refer to the range of
professionals—including recovery coaches and
other peer recovery support services specialists
—who may counsel, coach, or mentor people
who take OUD medication, although their titles,
credentials, and range of responsibilities vary. At
times, Part 4 refers to individuals as “clients.” For
other key terms, see Exhibit 4.1. Part 5 of this
TIP provides a full glossary and other resources
related to the treatment of OUD.
Counseling clients who take OUD medication
requires understanding:
• Basic information about OUD.
• The role and function of OUD medications.
• Ways to create a supportive environment that
helps clients work toward recovery.
• Counseling’s role within a system of
whole-person, recovery-oriented OUD care.
4-2
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.1. Key Terms
Addiction: As defned by the American Society of Addiction Medicine,3 “a primary, chronic disease of
brain reward, motivation, memory, and related circuitry” (p. 1). It is characterized by inability to consistently
abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with
one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other
chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical
Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic purposes, but it
commonly describes the more severe forms of OUD.
Care provider: Encompasses both healthcare professionals and other professionals who do not provide
medical services, such as counselors or providers of supportive services. Often shortened to “provider.”
Healthcare professionals: Physicians, nurse practitioners, physician assistants, and other medical
service professionals who are eligible to prescribe medications for and treat patients with OUD (i.e., until
October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, certifed nurse midwives).
The term “prescribers” also refers to these healthcare professionals.
Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs
and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as is
the typical standard of care in medical and psychiatric treatment of other chronic illnesses).
Mutual-help groups: Groups of people who work together on obtaining and maintaining recovery.
Unlike peer support (e.g., the use of recovery coaches), mutual-help groups consist entirely of people
who volunteer their time and typically have no offcial connection to treatment programs. Most are self-
supporting. Although 12-Step groups such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA)
are the most widespread and well-researched type of mutual-help groups, other groups may be available
in some areas. They range from groups affliated with a religion (e.g., Celebrate Recovery, Millati Islami) to
purely secular groups (e.g., SMART Recovery, Women for Sobriety).
Opioid misuse: The use of prescription opioids in any way other than as directed by a doctor; the use
of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5
Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity
at cell receptors in the central nervous system (CNS) that are normally stimulated by opioids. Mu-opioid
receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to
those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-
opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full
agonists, increasing their dose may not produce additional effects once they have reached their maximal
effect. At low doses, partial agonists may produce effects similar to those of full agonists.
Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the CNS
without producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g.,
naltrexone) can block the effects of exogenously administered opioids.
Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They
can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone).
Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and
Mental Health Services Administration (SAMHSA) certifcation and Drug Enforcement Administration
registration to administer and dispense opioid agonist medications that are approved by FDA to treat
opioid addiction. Currently, these include methadone and buprenorphine. Other pharmacotherapies,
such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide
adequate medical, counseling, vocational, educational, and other assessment and treatment services
either onsite or by referral to an outside agency or practitioner through a formal agreement.6
Continued on next page
4-3
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.1. Key Terms (continued)
Opioid use disorder (OUD): Per DSM-5,7 a disorder characterized by loss of control of opioid use,
risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do
not count toward the diagnosis in people experiencing these symptoms when using opioids under
appropriate medical supervision. OUD covers a range of severity and replaces what the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition, termed “opioid abuse” and “opioid dependence.”
An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11
symptoms in a 12-month period. (See Exhibit 2.13 and the Appendix in Part 2 for full DSM-5 diagnostic
criteria for OUD.)
Peer support: The use of peer support specialists in recovery to provide nonclinical (i.e., not requiring
training in diagnosis or treatment) recovery support services to individuals in recovery from addiction and
to their families.
Peer support specialist: Someone in recovery who has lived experience in addiction plus skills
learned in formal training. Peer support specialists may be paid professionals or volunteers. They are
distinguished from members of mutual-help groups because they maintain contact with treatment staff.
They offer experiential knowledge that treatment staff often lack.
Prescribers: Healthcare professionals who are eligible to prescribe medications for OUD.
Psychosocial support: Ancillary services to enhance a patient’s overall functioning and well-being,
including recovery support services, case management, housing, employment, and educational services.
Psychosocial treatment: Interventions that seek to enhance a patient’s social and mental
functioning, including addiction counseling, contingency management, and mental health services.
Recovery: A process of change through which individuals improve their health and wellness, live a
self-directed life, and strive to reach their full potential. Even individuals with severe and chronic SUDs
can, with help, overcome their SUDs and regain health and social function. Although abstinence from all
substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature.
Patients taking FDA-approved medication to treat OUD can be considered in recovery.
Recovery capital: The sum of the internal (e.g., motivation, self-effcacy, spirituality) and external (e.g.,
access to health care, employment, family support) resources that an individual can draw upon to begin
and sustain recovery from SUDs.
Recovery-oriented care: A service orientation that supports individuals with behavioral health
conditions in a process of change through which they can improve their health and wellness, live self-
directed lives, and strive to reach their full potential.
Relapse: A process in which a person with OUD who has been in remission experiences a return of
symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more
than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need
not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality.
Remission: A medical term meaning a disappearance of signs and symptoms of the disease.8 DSM-5
defnes remission as present in people who previously met OUD criteria but no longer meet any OUD
criteria (with the possible exception of craving).9 Remission is an essential element of recovery.
Return to opioid use: One or more instances of opioid misuse without a return of symptoms of
OUD. A return to opioid use may lead to relapse.
4-4
Medications for Opioid Use Disorder TIP 63
Setting the Stage
Since the 1990s, dramatic increases in controlled
medication prescriptions—particularly opioid pain
relievers—have coincided with increases in their
misuse.10 Since the mid-2000s, heroin11,12 and
fentanyl (mainly illicit formulations)13 consumption
has also sharply increased. People who turn to
illicit drugs after misusing opioid medications
have driven greater use of heroin and fentanyl,
which are cheaper and easier to obtain.
Approximately 1,500 OTPs currently dispense
methadone, buprenorphine, or both.14 They
may also offer naltrexone. Historically, OTPs were
the only source of OUD medication and offered
only methadone.
Buprenorphine is increasingly available in
general medical settings. Physicians, nurse
practitioners, and physician assistants (whether
or not they’re addiction specialists) can get
a federal waiver to prescribe buprenorphine.
These healthcare professionals can also prescribe
and administer naltrexone, which does not
require a waiver or OTP program certifcation.
Until October 1, 2023, qualifed clinical nurse
specialists, certifed registered nurse anesthe-
tists, and certifed nurse midwives also can
obtain a waiver to prescribe and administer
buprenorphine in offce-based settings.
People with OUD should have access to
the medication most appropriate for them.
Medication helps establish and maintain OUD
remission. By controlling withdrawal and cravings
and blocking the euphoric effects of illicit
opioids, OUD medication helps patients stop
illicit opioid use and resolve OUD’s psychosocial
problems. For some people, OUD medication
may be lifesaving. Ideally, patients with OUD
should have access to all three FDA-approved
pharmacotherapies. (See the “Quick Guide to
Medications” section for an overview of each
medication.)
Many patients taking OUD medication beneft
from counseling as part of their treatment.
Counseling helps people with OUD change how
they think, cope, react, and acquire the skills and
confdence needed for recovery. Patients may get
The counselor’s role with clients who
take OUD medication is the same as
it is with all clients who have SUDs:
Help them achieve recovery by
addressing addiction’s challenges and
consequences.
counseling from medication prescribers or staff
members in prescribers’ practices or by referral
to counselors at specialty addiction treatment
programs or in private practice. Exhibit 4.2
discusses recommending versus requiring counsel-
ing as part of medication treatment for OUD.
Distinguishing OUD From Physical
Dependence on Opioid Medications
According to DSM-5, 15 OUD falls under the
general category of SUDs and is marked by:
• Compulsion and craving.
• Tolerance.
• Loss of control.
• Withdrawal when use stops.
• Continued opioid use despite adverse
consequences.
Properly taken, some medications cause
tolerance and physical dependence.
Medications for some chronic illnesses (e.g.,
steroids for systemic lupus erythematosus) can
make the body build tolerance to the medica-
tions over time. If people abruptly stop taking
medications on which they’ve become physically
dependent, they can experience withdrawal
symptoms. This can be serious, even fatal.
Physical dependence on a prescribed,
properly taken opioid medication is distinct
from OUD and opioid addiction. OUD is a
behavioral disorder associated with loss of
control of opioid use, use despite adverse
consequences, reduction in functioning, and
compulsion to use. The professionals who
revised DSM-5 diagnostic criteria for OUD made
several signifcant changes. Among the most
notable was differentiating physical dependence
from OUD:
4-5
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.2. Recommending Versus Requiring Counseling
The TIP expert panel affrms that counseling and ancillary services greatly beneft many patients.
However, such counseling and ancillary services should target patients’ needs and shouldn’t be
arbitrarily required as a condition for receiving OUD medication (although they are required by
regulations in OTPs), especially when the benefts of medication outweigh the risks of not receiving
counseling.
The TIP expert panel recommends individualized treatment. Patients who choose to start medication
and medication management with their prescriber without adjunctive counseling and don’t adequately
respond to such treatment should be referred to adjunctive counseling and more intensive services as
needed.16
The law requires buprenorphine prescribers to be able to refer patients taking OUD medication to
counseling and ancillary services. Buprenorphine prescribers may meet this requirement by keeping a
list of referrals or by providing counseling themselves. The law doesn’t require naltrexone prescribers to
refer patients to additional services. However, FDA labels for both medications recommend counseling
as part of treatment.
Some treatment environments require counseling by regulation or contractual obligation. In other
cases, a healthcare professional may believe that a patient taking OUD medication would beneft
from counseling. Some healthcare professionals may require counseling, particularly if patients aren’t
responding well to medication.
OUD is often a chronic medical illness.17
Treatment isn’t a cure.
• Tolerance or withdrawal symptoms related
to FDA-approved medications appropriately
prescribed and taken to treat OUD (buprenor-
phine, methadone) don’t count toward
diagnostic criteria for OUD.
• If the individual is being treated with an OUD
medication and meets no OUD criteria other
than tolerance, withdrawal, or craving (but did
meet OUD criteria in the past), he or she is
considered in remission on medication.
Accepting this distinction is essential to
working with clients taking OUD medica-
tion. One common question about patients
taking medication for OUD is “Aren’t they still
addicted?” The new DSM-5 distinction makes
the answer to this question “No, they’re not still
addicted.” A person can require OUD medica-
tion and be physically dependent on it but still
be in remission and recovery from OUD.
Understanding the Benefts of
Medication for OUD
Medication is an effective treatment for
OUD.18,19,20 People with OUD should be referred
for an assessment for medication unless they
decline.21 To be supportive and effective when
counseling clients who could beneft from or who
take medication for OUD, know that:
• Treatment with methadone and buprenor-
phine is associated with lower likelihood of
overdose death compared with not taking
these medications.22,23,24,25,26
• Medication helps people reduce or stop
opioid misuse.27,28,29,30 As Jessica’s story in
Exhibit 4.3 shows, even if people return to
opioid use during treatment or don’t achieve
abstinence in the short term, medication
lessens misuse and its health risks (e.g.,
overdose, injection-related infections).31
• Patients taking FDA-approved medication
used to treat OUD can join residential or
outpatient treatment. Decades of clinical
4-6
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.3. Jessica’s Story About Medication
Jessica is a 32-year-old who unsuccessfully quit heroin dozens of times. She had been in and out of
treatment but says, “It just never stuck. I’d always start using again when I left the program.” Three years
ago, her primary care doctor started prescribing her buprenorphine. Now Jessica says:
Some days I pinch myself. I can’t believe I got my life back.
I tried quitting so many times but always got pulled back into the scene. Ever
since I’ve been on buprenorphine, I haven’t had any cravings. Even when
I’m around triggers, they just don’t set me off the same way. I’ve been able
to get a job and I’m starting to build a community of friends who don’t use.
The hardest part about being on buprenorphine is that my emotions aren’t
masked anymore. I have to feel all of the sadness and fear that I was avoiding
all these years. But it’s good. I’m getting a chance to work through it.”
experience in OTPs, which must provide
counseling, suggest that patients taking OUD
medication can fully participate in group and
individual counseling, both cognitively and
emotionally. Patients with concurrent SUDs
(involving stimulants or alcohol) can beneft
from residential treatment while continuing to
take their OUD medication.
• Randomized clinical trials indicate that
OUD medication improves treatment
retention and reduces illicit opioid use.32,33,34
Retention in treatment increases the oppor-
tunity to provide counseling and supportive
services that can help patients stabilize their
lives and maintain recovery.
• The longer patients take medication, the
less likely they are to return to opioid use,
whereas short-term medically supervised with-
drawal rarely prevents return to use:35,36,37,38,39
− Conducting short-term medically super-
vised withdrawal may increase the risk
of unintentional fatal overdose because
of decreased tolerance after withdrawal
completion.40,41
− Providing short-term medical treatment for
OUD is the same as treating a heart attack
without managing the underlying coronary
disease.
− Providing longer courses of medication
that extend beyond withdrawal can allow
patients to stabilize.
− Getting stabilized, which may take months
or even years, allows patients to focus on
building and maintaining a healthy lifestyle.
• Patients taking OUD medication can
achieve long-term recovery. People who
continue to take medication can be in remission
from OUD and live healthy, productive lives.42
Reviewing the Evidence on Counseling in
Support of Medication To Treat OUD
Dedicated counseling can help clients address
the challenges of extended recovery. For
clients who seek a self-directed, purposeful life,
counseling can help them:
• Improve problem-solving and interpersonal
skills.
• Find incentives for reduced use and
abstinence.
• Build a set of techniques to resist drug use.
• Replace drug use with constructive, rewarding
activities.
Moreover, evidence shows that counseling can
be a useful part of OUD treatment for people
who take OUD medication. Impact studies of
counseling for people with SUDs show that:
4-7
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
• Motivational enhancement/interviewing is
generally benefcial.43 This approach helps
get people into treatment. It also supports
behavior change and, thus, recovery.
• Cognitive–behavioral therapy (CBT) has
demonstrated effcacy in the treatment of
SUDs, whether used alone or in combination
with other strategies.44 Clinical trials have not
shown that CBT added to buprenorphine
treatment with medical management is asso-
ciated with signifcantly lower rates of illicit
opioid use.45,46 However, a secondary analysis
of one of those trials found that CBT added
to buprenorphine and medical management
was associated with signifcantly greater
reduction in any drug use among participants
whose OUD was primarily linked to misuse
of prescription opioids than among those
whose OUD involved only heroin.47 Thus, CBT
may be helpful to those patients receiving
buprenorphine treatment who have nonopioid
drug use problems.
• Case management helps establish the
stability necessary for SUD remission.48,49,50
Case management helps some people in SUD
treatment get or sustain access to services
and necessities, such as:
− Food.
− Shelter.
− Income support.
− Legal aid.
− Dental services.
− Transportation.
− Vocational services.
• Family therapy can address SUDs and
various other family problems (e.g., family
confict, unemployment, conduct disorders).
Several forms of family therapy are effective
with adolescents51 and can potentially address
family members’ biases about use of medica-
tion for OUD.52
• There is more research on combined
methadone treatment and various psycho-
social treatments (e.g., different levels of
counseling, contingency management) than
on buprenorphine or naltrexone treatment
in offce-based settings. More research is
needed to identify the best interventions to
use with specifc medications, populations,
and treatment phases in outpatient settings.53
• Motivational intervention, case manage-
ment, or both can improve likelihood of
entry into medication treatment for OUD
among people who inject opioids, according
to a systematic review of 13 studies plus data
from a prior systematic review.54
• Clinical trials have shown no differences in
outcomes for buprenorphine with medical
management between participants who get
adjunctive counseling and those who don’t
(i.e., prescriber-provided guidance focused
specifcally on use of the medication).55,56,57,58
RESOURCE ALERT
Principles of Effective Treatment
In its Principles of Drug Addiction Treatment, the
National Institute on Drug Abuse lists 13 principles
of effective treatment (p. 2).59 Two principles that
pertain to counseling are:
in returning to productive functioning in the
family, workplace, and society.”
• “Effective treatment attends to multiple needs
of the individual, not just his or her drug
abuse. To be effective, treatment must address
the individual’s drug abuse and any associated
medical, psychological, social, vocational,
and legal problems. It is also important that
treatment be appropriate to the individual’s
age, gender, ethnicity, and culture.”
• “No single treatment is effective for everyone.
Treatment varies depending on the type of drug
and the characteristics of the patients. Matching
treatment settings, interventions, and services
to an individual’s particular problems and
needs is critical to his or her ultimate success
4-8
Medications for Opioid Use Disorder TIP 63
RESOURCE ALERT
Recovery-Oriented Treatment
Recovery-Oriented Methadone Maintenance: This guide by Bamber and White is the most thorough
document on this topic currently available and is applicable to clients receiving other medications
for OUD (www.williamwhitepapers.com/pr/2011%20Bamber-White%20Dialogue%20on%20Recovery-
Oriented%20Methadone%20Maintenace.pdf).
Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for
Recovery-Oriented Methadone Maintenance (www.williamwhitepapers.com/pr/Recovery-oriented%20
Methadone%20Maintenance%20Best%20Practice%20Guidelines%202014%20-%20CCBHO.pdf)
and Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for
Buprenorphine and Suboxone (www.williamwhitepapers.com/pr/Community%20Care%20Best%20
Practice%20Guidelines%20for%20Buprenorphine%20and%20Suboxone%202014.pdf) outline phase-
specifc tasks and accompanying strategies for programs that provide services to clients who take these
medications.
Yet those trials:
− Relied on well-structured medical manage-
ment sessions that may not be typical in
practice.
− Excluded patients with certain co-occurring
disorders or factors that complicated
treatment.
• Benefts from counseling may depend on
factors such as the number of sessions and
adherence.60
Using a Recovery-Oriented Approach to
Treating Patients With OUD
Counseling for OUD gives patients tools to
manage their illness, achieve and sustain
better health, and improve their quality of
life. There are limits to how much medication
alone can accomplish. OUD medication will
improve quality of life,61 but many clients in
addiction treatment have complex issues that
may decrease quality of life, such as:
• Other SUDs (e.g., alcohol use disorder,
cannabis use disorder).62,63,64
• Mental distress65 (i.e., high levels of
symptoms) and disorders66,67,68 (e.g., major
depressive disorder, posttraumatic stress
disorder).
• Medical problems (e.g., hepatitis,
diabetes).69
• History of trauma.70,71
• Poor diet, lack of physical activity, or
both.72
• Lack of social support.73
• Unemployment.74
Acknowledge many pathways to recovery
Recovery occurs via many pathways.75 OUD
medication may play a role in the beginning,
middle, or entire continuum of care.
Support clients in making their own
informed decisions about treatment.
Counselors don’t need to agree with clients’
decisions but must respect them. Educate
new clients about:
• Addiction as a chronic disease infuenced
by genetics and environment.
• How medications for OUD work.
• What occurs during dose stabilization.
• The benefts of longer term medication
use and the risks of abruptly ending
treatment.
4-9
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
SAMHSA’S GUIDING PRINCIPLES
OF RECOVERY76
• Recovery emerges from hope.
• Recovery is person driven.
• Recovery occurs via many pathways.
• Recovery is holistic.
• Recovery is supported by peers and allies.
• Recovery is supported through relationships
and social networks.
• Recovery is culturally based and infuenced.
• Recovery is supported by addressing trauma.
• Recovery involves individual, family, and
community strengths and responsibilities.
• Recovery is based on respect.
Promote recovery for clients with OUD
Focus on addressing personal and practical
problems of greatest concern to clients, which
can improve their engagement in treatment.77
Recovery supports can sustain the progress
clients made in treatment and further improve
their quality of life. Addressing the full range of
client needs can improve clients’ quality of life
and lead to better long-term recovery outcomes.
A recovery-oriented approach to traditional SUD
counseling may help address client needs.78,79
Increasing recovery capital supports long-term
abstinence and improved quality of life, espe-
cially for clients who decide to stop medication.
Clients with substantial periods of abstinence
from illicit drugs identify these strategies for
increasing recovery capital as helpful:80,81,82
• Forging new relationships with friends/family
• Obtaining support from friends, family,
partners, and communities
• Using positive coping strategies
• Finding meaning or a sense of purpose in life
• Engaging in a church or in spiritual practices
• Pursuing education, employment, or both
• Engaging in new interests or activities (e.g.,
joining a community group, exercising)
• Building confdence in ability to maintain
RESOURCE ALERT
Decision-Making Tool
The Shared Decision-Making Tools page is a
SAMHSA web-based resource (www.samhsa.
gov/brss-tacs/recovery-support-tools/shared-
decision-making) to help people with OUD
make decisions about treatment and recovery.
abstinence (i.e., increasing abstinence-related
self-effcacy)
• Finding ways to help other individuals who are
new to recovery
Help clients further grow recovery capital
by offering or connecting them to a range of
services, such as:
• Ancillary services (e.g., vocational rehabilitation,
supported housing).
• Additional counseling.
• Medical services.
• Mental health services.
Provide person-centered care
Clients’ confdence in their ability to stay
away from illicit substances, or self-effcacy,
is an important factor in successful change. In
person-centered care, also known as patient-
centered care:
• Clients control the amount, duration, and
scope of services they receive.
• They select the professionals they work with.
• Care is holistic; it respects and responds to
clients’ cultural, linguistic, and socioenviron-
mental needs.83
• Providers implement services that recognize
patients as equal partners in planning, devel-
oping, and monitoring care to ensure that it
meets each patient’s unique needs.84
4-10
Medications for Opioid Use Disorder TIP 63
The confrontational/expert model that
characterized much of SUD treatment
in the past may harm some patients
and inhibit or prevent recovery.85
A person-centered approach to OUD
treatment empowers clients in making
decisions, such as:86
• Whether to take OUD medication.
• Which medication to take.
• Which counseling and ancillary services
to receive.
Fragmented healthcare services are less
likely to meet the full range of patients’
needs. Integrated medical and behavioral
healthcare delivery provides patient-focused,
comprehensive treatment that meets the wide
range of symptoms and service needs that
patients with OUD may have. Signifcant demand
remains for better integrated and coordinated
SUD treatment (including OTP), medical, and
mental health services.87 Such improvements are
RESOURCE ALERT
particularly important for the many individuals
with co-occurring substance use and mental
disorders who receive OUD medication.88,89 In
a randomized trial of methadone patients with
co-occurring mental disorders receiving onsite
versus offsite mental health services, those
receiving services onsite had less psychiatric
distress at follow-up.90
Promote family and social support
Support from family and friends can be the
most important factor in long-term recovery,
according to many people who have achieved
long-term recovery from OUD.91,92 Support from
intimate partners helps all clients, especially
women, avoid return to opioid use.93,94 But the
more people in clients’ social networks who use
drugs, the more likely clients are to return to
use.95,96
Most clients are willing to invite a substance-
free family member or friend to support
their recovery.97 Most have at least one nearby
family member who does not use illicit drugs.98
A client’s community may provide a cultural
context for their recovery and culturally specifc
supports that may not otherwise be available in
treatment.99
Help clients develop and support positive
relations with their families by:
• Suggesting that clients invite family and
friends to aid in the recovery planning process
(Exhibit 4.4).
• Emphasizing the importance of relationships
with family and friends who actively support
recovery.
• Supporting clients in mending broken
relationships with loved ones.
• Helping clients cut ties with individuals who
still use drugs or enable clients’ drug use.
• Encouraging clients to build new relationships
that support recovery.
Treatment Guidance for Co-
Occurring Substance Use and
Mental Disorders
TIP 42, Substance Use Disorder Treatment for
People With Co-Occurring Disorders, provides
SUD treatment strategies for people with mental
disorders (https://store.samhsa.gov/product/
tip-42-substance-abuse-treatment-persons-co-
occurring-disorders/PEP20-02-01-004).
Integrated Treatment for Co-Occurring
Disorders Evidence-Based Practices KIT provides
practical guidance for integrating mental health
services and SUD treatment
(https://store.samhsa.gov/product/Integrated-
Treatment-for-Co-Occurring-Disorders-
Evidence-Based-Practices-EBP-KIT/
SMA08-4366).
4-11
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.4. Engaging Reluctant Family Members in a Client’s
Treatment
If the client agrees and has signed the appropriate releases, help even reluctant family members engage
in the client’s treatment to offer support. To reach out to family members who hesitate to engage, try to:
• Recognize that they have been harmed by
their family member’s substance use and that
their participation in his or her recovery can help
them heal, too.
• Ask them to recall some positive experiences
they have had with the client.
• Introduce them to mutual-help groups and
other supports for families (e.g., Nar-Anon, Learn
to Cope, Parents of Addicted Loved Ones Group).
Ensure that suggested groups don’t have a
negative option medication bias.
Provide trauma-informed care
Trauma-informed service requires providers to
realize the signifcance of trauma. According to
SAMHSA,100 trauma-informed counselors know
what trauma is and also:
• Understand how trauma can affect clients,
families, and communities.
• Apply knowledge of trauma extensively and
consistently in both practice and policy.
• Know ways to promote recovery from trauma.
• Recognize the signs and symptoms of trauma
in clients, families, staff members, and others.
• Resist things that may retraumatize or harm
clients or staff.
Incorporate trauma-informed principles of
care into recovery promotion efforts, because:
• Trauma histories and trauma-related disorders
may increase clients’ risk for various problems,
including early drop-out from treatment101 and
greater problems with pain.102
• Childhood trauma is highly prevalent among
people with OUD.103,104
• People often suffer multiple traumas during
opioid misuse.105
• Help them understand OUD, the treatment
process, and medication’s role in recovery.
This knowledge can keep family members
from pressuring the client to taper medication
prematurely.
• Hold multifamily therapy groups or informal
discussion sessions for families (with or without
clients present) so that family members can learn
from one another and share their experiences.
• Offer family or couples therapy as an option
for additional support.
• An intervention that integrated trauma
treatment and standard care (which goes
further than the trauma-informed care
detailed here) had better outcomes than
standard care alone in a diverse group of
women treated in various settings, including
an OTP.106
RESOURCE ALERT
Trauma-Informed Care TIP
TIP 57, Trauma-Informed Care in Behavioral
Health Services, has more information on
providing trauma-informed care in SUD
treatment programs (https://store.samhsa
.gov/product/TIP-57-Trauma-Informed-Care
-in-Behavioral-Health-Services/SMA14-4816).
4-12
Medications for Opioid Use Disorder TIP 63
Quick Guide to Medications
This section introduces the neurochemistry
and biology of OUD and the medications that
treat it. Reading this section will familiarize
counselors with terminology healthcare profes-
sionals may use in discussing patients who take
OUD medication (see also Exhibit 4.1 and the
comprehensive glossary in Part 5).
Understanding the Neurobiology of OUD
Opioid receptors are a part of the body’s
natural endorphin system. Endorphins are
chemicals our bodies release to help reduce our
experience of pain. They can also contribute to
euphoric feelings like the “runner’s high” that
some people experience. When endorphins or
opioids bind to opioid receptors, the receptors
activate, causing a variety of effects.
After taking opioids, molecules bind to and
activate the brain’s opioid receptors and
release dopamine in a brain area called the
nucleus accumbens (NAc), causing euphoria. Like
opioid receptors, the NAc has a natural, healthy
function. For example, when a person eats,
the NAc releases dopamine to reinforce this
essential behavior. The NAc is a key part of the
brain’s reward system.
Opioid use leads to an above-normal release
of dopamine, essentially swamping the
natural reward pathway and turning the brain
strongly toward continued use. The brain also
learns environmental cues associated with this
dopamine release. It associates specifc people,
places, and things (e.g., music, drug parapherna-
lia) with the euphoria; these environmental cues
then become triggers for drug use.
Intermittent opioid use causes periods of
euphoria followed by periods of withdrawal.
The brain’s strong draw toward euphoria drives
repeated and continued use. Few people with
OUD reexperience the euphoria they obtained
early in their opioid use, yet they continue to
seek it.
Changes in brain function that result from
repeated drug use cause a person who once
took the drug for euphoria to seek it out of
habit, then compulsion. People with OUD
use opioids to stave off withdrawal. Without
opioids, the person feels dysphoric and physically
ill, only feeling normal by taking opioids again.
At the same time, other areas of the brain begin
to change:107
• The amygdala, which is associated with
feelings of danger, fear, and anger, becomes
overactive.
• The frontal cortex, which is associated
with planning and self-control, becomes
underactive.
• The ability to control impulses diminishes,
and drug use becomes compulsive.
• The need to escape the discomfort and
intensely negative emotional states of
withdrawal becomes the driving force of
continued use.
Even after opioid use stops, brain changes
linger. A person’s ability to make plans and
manage impulses stays underactive. That’s why
return to substance use is very common even
after a period of abstinence.
Medications for OUD promote emotional,
psychological, and behavioral stabilization.
By acting directly on the same opioid receptors
as misused opioids (but in different ways),
medications can stabilize abnormal brain
activity.
Learning How OUD Medications Work
The following sections describe how each of
the OUD medications functions (Exhibit 4.5; see
also Part 3 of this TIP for greater detail). Discuss
questions or concerns about a patient’s medi-
cation, side effects, or dosage with the patient’s
prescriber after getting the patient’s consent.
4-13
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.5. FDA-Approved Medications Used To Treat OUD: Key Points
MEDICATION
HOW IT’S
TAKEN
WHY IT
WORKS SIDE EFFECTS NOTES
Buprenorphine Tablet dissolved
under the
tongue or flm
dissolved under
the tongue
or against
the inside of
the cheek.
Taken once
daily, every
other day, or 3
Partially
activates
the opioid
receptor.
Reduces
craving
and
blocks the
euphoric
effect of
opioids.
Can cause constipation, headache,
nausea, insomnia, excessive
sweating, or opioid withdrawal.
Overdose is possible but less
likely than with methadone.
Overdose death risk is increased
if buprenorphine is taken with
alcohol or intravenously in
combination with benzodiazepines
or other CNS depressants.
Less sedating
than methadone.
Prescribers must
have a special
SAMHSA waiver but
don’t need to be
part of a federally
certifed OTP. Can
be prescribed
through pharmacies
or provided via
times a week.
It also comes
as an implant
that lasts 6
months or as an
injection that
lasts 1 month.
Neonatal abstinence syndrome
(NAS)
OTPs. The implant
and injection can
only be prescribed
by waivered
providers who have
completed REMS
training.
Methadone Liquid or tablet
once daily.
Dose may
be divided
for twice-
daily dosing
if medically
necessary.
Fully
activates
the opioid
receptor.
Reduces
craving
and
blocks the
euphoric
effect of
opioids.
Can cause constipation, sleepiness,
sweating, swelling of hands and
feet, sexual dysfunction, heart
arrhythmias, low blood pressure,
fainting, and substance misuse.
Can cause overdose death if
increased too rapidly, taken in a
much higher than usual dose, or
taken concurrently with some
substances and medications,
particularly CNS depressants such
as alcohol or benzodiazepines.
NAS
Initially requires
visits 6 to 7 times
per week to an
OTP. Patients
can decrease
attendance
gradually based on
time in treatment
and clinical stability.
Naltrexone Daily tablet (can
also be taken 3
times a week)
or monthly
injection in
buttock.
Occupies
the opioid
receptors.
Reduces
craving
and
blocks the
euphoric
effect of
opioids.
Can cause nausea, headache,
dizziness, fatigue, liver toxicity,
depression and suicidality, muscle
cramps, fainting, and loss of or
decreased appetite or other
appetite disorders; in the extended-
release injectable formulation, can
cause pain, swelling, and other
complications at the injection site.
Patient must complete withdrawal
and stay opioid abstinent for
at least 7 days before starting
naltrexone and longer (e.g., 10 or
more days) for long-acting opioids,
such as methadone.
Tablets are rarely
effective. Monthly
injections are more
effective than
tablets.
4-14
Medications for Opioid Use Disorder TIP 63
Buprenorphine
Buprenorphine reduces opioid misuse,
HIV risk behaviors, and risk of overdose
death.108,109,110,111 Buprenorphine only partially
activates opioid receptors; it is a partial agonist.
It binds to and activates receptors suffciently
to prevent craving and withdrawal and to block
the effects of illicit opioids. Appropriate doses
of buprenorphine shouldn’t make patients feel
euphoric, sleepy, or foggy headed.
Buprenorphine has the beneft of a ceiling
effect. Its effectiveness and sedation or
respiratory effects don’t increase after a
certain dosing level, even if more is taken. This
lowers risk of overdose and misuse.112 Groups
at particular risk for buprenorphine overdose
include children who accidentally ingest the
medication113 and patients who also use CNS
depressants like benzodiazepines or alcohol.114,115
(See Part 3 of this TIP for more information
on concurrent use of CNS depressants and
buprenorphine.)
Buprenorphine is available outside of OTPs,
through non-OTP healthcare settings (e.g.,
physicians’ offces, outpatient drug treatment
programs). Healthcare professionals (including
nurse practitioners and physician assistants, per
the Comprehensive Addiction and Recovery Act
of 2016, and, until October 1, 2023, qualifed
clinical nurse specialists, certifed registered
nurse anesthetists, and certifed nurse midwives,
per the SUPPORT for Patients and Communities
Act of 2018) can prescribe it outside of an OTP,
provided they have a specifc federal waiver.
This is often referred to as “being waivered” to
prescribe buprenorphine.
Buprenorphine can cause opioid withdrawal
in patients who have recently taken a full
opioid agonist (e.g., heroin, oxycodone). This
occurs because buprenorphine pushes the full
opioid activator molecules off the receptors and
replaces them with its weaker, partially activating
effect. For this reason, patients must be in opioid
withdrawal when they take their frst dose of
buprenorphine.
The most common buprenorphine formulation
contains naloxone to reduce misuse. Naloxone
is an opioid antagonist. It blocks rather than
activates receptors and lets no opioids sit on
receptors to activate them. Naloxone is poorly
absorbed under the tongue/against the cheek,
so when taking the combined medication as
directed, it has no effect. If injected, naloxone
causes sudden opioid withdrawal.
Buprenorphine comes in two forms that melt
on the inside of the cheek or under the tongue:
flms (combined with naloxone) or tablets (bu-
prenorphine/naloxone or buprenorphine alone).
For treatment of OUD, patients take the flms or
tablets once daily, every other day, or three times
a week. Various companies manufacture these
forms of the medication. Some are brand name,
and some are generic. The different kinds vary in
strength or number of milligrams, but they have
been designed and tested to provide roughly the
same amount of medication as the frst approved
product (Exhibit 3A.5 in Part 3).
Buprenorphine is also available in a long-
acting implant and long-acting injection that
specially trained healthcare professionals place
under the skin (subdermal implant) and an ex-
tended-release formulation that is administered
under the skin (subcutaneous injection). The
implant is appropriate for patients who have been
stable on low doses of the flms or tablets. It lasts
for 6 months and can be replaced once after 6
months. The extended release injection lasts for 1
month and can be repeated monthly. It is appro-
priate for patients who have been stabilized on
the flms or tablets for at least 7 days.
Healthcare professionals with waivers can
prescribe buprenorphine. Physicians who take
an 8-hour training and get a waiver can prescribe
buprenorphine. Nurse practitioners and physician
assistants are eligible to apply for waivers after
24 hours of training. Until October 1, 2023,
clinical nurse specialists, certifed registered nurse
anesthetists, and certifed nurse midwives also
are eligible to apply for waivers after 24 hours of
training. Recent buprenorphine practice guide-
lines provide an exemption to providers who are
4-15
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
state licensed, possess a valid DEA registration,
and wish to treat no more than 30 patients with
buprenorphine. The “traditional” pathway of
obtaining a waiver by undergoing the 8-hour
training still exists and is required for providers
who wish to treat more than 30 patients.116
Providers who wish to deliver buprenorphine
implants must receive special training on how to
insert and remove them.
Buprenorphine can cause side effects including
constipation, headache, nausea, and insomnia.
These often improve over time and can be
managed with dosage adjustments or other
approaches.
Methadone
Methadone is highly effective. Many studies
over decades of research show that it:117,118,119
• Increases treatment retention.
• Reduces opioid misuse.
• Reduces drug-related HIV risk behavior.
• Lowers risk of overdose death.
Methadone is slow in onset and long acting,
avoiding the highs and lows of short-acting
opioids. It is a full agonist. Patients who take
the same appropriate dose of methadone daily
as prescribed will neither feel euphoric from the
medication nor experience opioid withdrawal.
Methadone is an oral medication that is taken
daily under observation by a nurse or phar-
macist and under the supervision of an OTP
physician. Methadone is available as a liquid
concentrate, a tablet, or an oral solution made
from a dispersible tablet or powder.
Methadone blunts or blocks the euphoric effects
of illicit opioids because it occupies the opioid
receptors. This “opioid blockade” helps patients
stop taking illicit opioids because they no longer
feel euphoric if they use illicit opioids. When on a
proper dose of methadone, patients can:
• Keep regular schedules.
• Lead productive, healthy lives.
• Meet obligations (family, social, work).
Methadone can lead to overdose death in
people who use a dose that’s considerably
higher than usual, as methadone is a full
agonist. People who don’t usually take opioids
or have abstained from them for a while could
overdose on a fairly small amount of methadone.
Thus, patients start on low doses of methadone
and gradually adjust upward to identify the
optimal maintenance dose level.
Patients must attend a clinic for dose adminis-
tration 6 to 7 days per week during the start
of treatment. Healthcare professionals can thus
observe patients’ response to medication and
discourage diversion to others. Visit frequency
can lessen after patients spend time in treatment
and show evidence of progress.
Methadone can cause certain side effects.
Common potential side effects of methadone
include:
• Constipation.
• Sleepiness.
• Sweating.
• Sexual dysfunction.
• Swelling of the hands and feet.
Sleepiness can be a warning sign of potential
overdose. Patients who are drowsy should
receive prompt medical assessment to determine
the cause and appropriate steps to take—which
may require a reduction in methadone dose.
Some patients may appear sleepy or have
trouble staying awake when idle, even if there
is no immediate danger of evolving overdose.
These patients may need a lower dose or may
be taking other prescribed or nonprescribed
medications (e.g., benzodiazepines, clonidine)
that are interacting with the methadone.
Naltrexone
Naltrexone stops opioids from reaching and
activating receptors, preventing any reward
from use. Naltrexone is an antagonist of the
opioid receptors—it does not activate them at
all. Instead, it sits on the receptors and blocks
other opioids from activating them.
4-16
Medications for Opioid Use Disorder TIP 63
Naltrexone appears to reduce opioid craving120
but not opioid withdrawal (unlike buprenorphine
and methadone, which reduce both craving
and withdrawal). Someone starting naltrexone
must be abstinent from short-acting opioids for
at least 7 days and from long-acting opioids
for 10 to 14 days before taking the frst dose.
Otherwise, it will cause opioid withdrawal,
which can be more severe than that caused by
reducing or stopping opioid use.
Naltrexone comes in two forms: tablet and
injection.
• Patients take oral naltrexone as tablets daily
or three times per week. Tablets are rarely
effective, as patients typically stop taking
them after a short time.121,122,123
• Highly externally monitored populations
in remission may do well with the
tablet,124,125,126 such as physicians who have
mandatory frequent urine drug testing and
are at risk of losing their licenses.
• The injected form is more effective than the
tablet because it lasts for 1 month. Patients
can come to a clinic to receive an intramuscu-
lar injection in their buttock.
Naltrexone can produce certain side effects,
which may include:
• Nausea.
• Headache.
• Dizziness.
• Fatigue.
For the extended-release injectable formulation,
potential reactions at the injection site include:
• Pain.
• Bumps.
• Blistering.
• Skin lesions (may require surgery).
Knowing What Prescribers Do
The following sections will help explain the role
healthcare professionals play in providing each
OUD medication as part of collaborative care.
Part 3 of this TIP offers more detailed clinical
information.
Administer buprenorphine
Patients typically begin buprenorphine in
opioid withdrawal. Patients may take their frst
dose in the prescriber’s offce so the prescriber
can observe its initial effects. Increasingly often,
patients take their frst dose at home and follow
up with prescribers by phone. Most people are
stable on buprenorphine dosages between 8 mg
and 24 mg each day.
Patients who take buprenorphine visit their
prescriber regularly to allow monitoring of
their response to treatment and side effects
and to receive supportive counseling. The
visits may result in specifc actions, such as
adjusting the dosage or making a referral for
psychosocial services. Stable patients may obtain
up to a 30-day prescription of this medication
through community pharmacies. Visits may
include urine drug testing. Early in treatment,
patients typically see their prescribers at least
weekly. Further along, they may visit prescribers
every 1 to 2 weeks and then as infrequently as
once a month or less.
The prescriber will make dosage adjustments
as needed, reducing for side effects or increasing
for unrelieved withdrawal or ongoing opioid
misuse. OTPs that provide buprenorphine
will typically follow a similar process, with the
principal difference being that the program
will administer or dispense the medication
rather than the patient flling a prescription at
a pharmacy.
Administer methadone
Only SAMHSA-certifed OTPs may provide
methadone by physician order for daily
observed administration onsite or for self-
administration at home by stable patients.127
The physician will start patients on a low dose
of methadone. People in early methadone
treatment are required by federal regulation
to visit the OTP six to seven times per week to
take their medication under observation. The
physician will monitor patients’ initial response
to the methadone and slowly increase the
dose until withdrawal is completely relieved for
24 hours.
4-17
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
A prescriber can’t predict at the start of
treatment what daily methadone dose will
work for a patient. An effective dose is one
that eliminates withdrawal symptoms and most
craving and blunts euphoria from self-
administered illicit opioids without producing
sedation. On average, higher dosages of
methadone (60 mg to 100 mg daily) are
associated with better outcomes than lower
dosages.128,129 That said, an effective dose of
methadone for a particular patient can be above
or below that range.
The prescriber will continue to monitor the
patient and adjust dosage slowly up or down
to fnd the optimum dose level. The dose may
need further adjustment if the patient returns
to opioid use, experiences side effects such
as sedation, starts new medications that may
interact with methadone, or has a change in
health that causes the previously effective dose
to become inadequate or too strong.
If patients taking methadone drink heavily
or take sedatives (e.g., benzodiazepines),
physicians may:
• Treat the alcohol misuse.
• Refer to a higher level of care.
• Address comorbid anxiety or depression.
• Decrease dosage to prevent overdose.
Administer naltrexone
To avoid severe withdrawal, prescribers
will ensure that patients are abstinent from
opioids at least 7 to 10 days before initiating
or resuming naltrexone. Prescribers may require
longer periods of abstinence for patients tran-
sitioning from buprenorphine or methadone to
naltrexone.
Prescribers typically take urine drug screens
to confrm abstinence before giving naltrex-
one. Healthcare professionals can confrm absti-
nence through a “challenge test” with naloxone,
a short-acting opioid antagonist.
Healthcare professionals manage withdrawal
symptoms with nonopioid medication.
Prescribers are prepared to handle withdrawal
caused by naltrexone despite a period of
abstinence.130 Ideally, they administer the frst
injection before patients’ release from residential
treatment or other controlled settings (e.g.,
prison) so qualifed individuals can monitor them
for symptoms of withdrawal.
Healthcare professionals typically see patients
at least monthly to give XR-NTX injections.
For those taking oral naltrexone, prescribers
schedule visits at their discretion. Thus, urine
drug testing may be less frequent for these
patients than for patients taking buprenorphine.
But periodic drug testing should occur.
There is only one dose level for injected
naltrexone,131 so prescribers cannot adjust the
dose. However, they can slightly shorten the
dosing interval if the medication’s effectiveness
decreases toward the end of the monthly dosing
interval. If the patient is having side effects or
intense cravings, the prescriber may recommend
switching to a different medication.
Set expectations
Ideally, prescribers will collaborate with
counselors and other care providers involved
in patients’ care to set reasonable patient
expectations. Medications can effectively treat
OUD, but they don’t treat other SUDs (save
naltrexone, also FDA-approved to treat alcohol
use disorder). Patients may still need:
• Counseling for psychosocial issues.
• Social supports/treatment to get back on track.
• Medications, therapy, or both for co-occurring
conditions.
Collaboration between all involved healthcare
providers helps patients understand the
OUD treatment timeline, which generally lasts
months or years. Courses of medically supervised
withdrawal or tapering are considerably less
Patients may still beneft from the
counseling you can offer in addition
to care from other providers, even if
you can’t communicate with those
providers directly.
4-18
Medications for Opioid Use Disorder TIP 63
effective than longer term maintenance treatment
with buprenorphine or methadone and are often
associated with return to substance use and a
heightened risk of overdose.132,133,134,135
Counselor–Prescriber
Communications
OUD medication can support counselors’ work
with clients who have OUD, and counseling
supports the work prescribers do with them.
Good communication facilitates mutually
supportive work (Exhibit 4.6). A counselor will
probably:
• See patients more frequently than prescribers.
• Have a more complete sense of patients’
issues.
• Offer providers valuable context and
perspective.
• Help patients take medications appropriately.
• Ensure that patients receive high-quality care
from their other providers.
Obtaining Consent
Get written consent from patients allowing
communication directly with their providers
(unless the counselor and the providers work
Good communication with prescribers
and other treatment team members
allows everyone to work together to:
• Assess patient progress.
• Change treatment plans if needed.
• Make informed decisions about
OUD medication.
in the same treatment program). The consent
must explicitly state that the patient allows
the counselor to discuss substance-use-related
issues. It should also specify which kinds of in-
formation the counselor can share (e.g., medical
records, diagnoses). Consent forms must comply
with federal and state confdentiality laws that
govern the sharing of information about patients
with SUDs.136,137
Carefully protect any identifying informa-
tion about patients and their medical and
treatment information. Don’t send such infor-
mation through unsecured channels, such as:
• Text messaging.
• Unsecure, unencrypted emails.
• Faxes to unsecured machines.
EXHIBIT 4.6. Example of Counselor–Prescriber Communication
Counselor: Dr. Smith, thank you for referring Jeff to my counseling practice. I’d like to review with you
the elements of the treatment plan we’ve developed.
Prescriber: That would be really helpful.
Counselor: We agreed to meet weekly while he’s getting stabilized on the buprenorphine. The initial
focus of our sessions will be helping Jeff expand his recovery support network.
Prescriber: I’m glad to hear that you’re following up on that. My nurse reported that he’s alone in the
waiting room before his appointments, and he also mentioned to me that he doesn’t
have anybody to talk with.
Counselor: I suggested a support group for people taking buprenorphine that’s in his neighborhood.
We’ve also begun talking about recreational activities that can help him fll the time he
used to spend with drug-using friends.
Prescriber: I’ll reinforce your suggestions when he comes in this Friday.
Counselor: Also, he seems confused about where the flm goes in his mouth. I urged him to discuss
that with you.
Prescriber: I’ll make a note to go over that with him again on Friday.
4-19
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
Phone calls are the most secure way to discuss
patient cases, although it may be more conve-
nient to reach out to healthcare professionals
frst through email.
Structuring Communications With
Prescribers
Regular, structured communication can
improve the fow of information between
treatment teams. Some multidisciplinary
programs produce regular reports for prescribers
about patient progress. Exhibit 4.7 provides
some strategies for discussing patient care with
healthcare professionals.
Helping Clients Overcome Challenges in
Accessing Resources
By collaborating with healthcare professionals in
OUD care, counselors can help clients overcome
challenges they face in obtaining treatment, such
as:
• Ability to pay for OUD medication.
Counselors are often already skilled in helping
clients address treatment costs (e.g., facil-
itating Medicaid applications, linking them
to insurance navigators). Try to refer clients
who face diffculty meeting prescription
costs or copays back to the agency’s fnancial
department for sliding scale adjustments and
ability-to-pay assessments. Also try to help
patients fnd and apply for relevant pharma-
ceutical company medication prescription
plans.
• Transportation. Options to offer clients may
include:
− Providing vouchers for public
transportation.
− Providing information on other subsidized
transportation options.
− Linking clients to peer support specialists
and case managers who can arrange
transportation.
− Assisting eligible clients in navigating
Medicaid to obtain transportation services.
− If available, arranging for telehealth services
to overcome clients’ transportation barriers.
• Access to medication in disaster situations.
Counselors can review options with patients
for obtaining prescription replacements
and reflls or daily medicine dosing under
various scenarios. This could include if their
usual clinic or primary pharmacy is closed or
if they’re relocated without notice because
of an unforeseen emergency. Also advise
patients on the items to take with them in
such scenarios to facilitate reflls from a new
EXHIBIT 4.7. Tips for Discussing Patient Care With Prescribers
• Identify the patient. Once the counselor has established secure communication through encrypted
email or by phone, he or she should state the patient’s name, date of birth, and medical record number
(if obtained).
• Let prescribers know up front the purpose of the call. Begin by clearly describing the question or
concern leading to the call. If it is simply to establish contact because of a shared patient, that’s fne.
• Share any relevant information about the patient (if the patient has consented). If there is a concern
about a side effect, for example, describe observed changes to the healthcare professional. If there is a
concern about return to opioid use, describe which elements of the patient’s behavior are worrisome.
• Work together to build a shared understanding of the patient’s situation. The counselor likely has key
information about the patient that the prescriber does not have, and vice versa.
• Discuss next steps with the healthcare provider before ending any communication to help coordinate
patient care. Consider scheduling a check-in with each other to assess patient progress.
4-20
Medications for Opioid Use Disorder TIP 63
medication-dispensing facility. Key materials
include:
− Photo identifcation.
− Medication containers of currently pre-
scribed medications (even if empty).
− Written prescriptions.
− Packaging labels that contain dosage,
prescriber, and refll information.
− Any payment receipts that contain
medication information.
To overcome systemic barriers, help enact
collaborative policies and procedures. Work
with program management and the community
at large to address the following issues:
• Connection to treatment: Counselors may
be able to participate in community efforts
to ensure that information on how to obtain
treatment for OUD is available wherever
people with OUD:
− Gather (e.g., all-night diners, bars, free health
clinics, injection equipment exchanges).
− Seek help (e.g., emergency departments,
houses of worship, social service agencies).
− Reveal a need for help (e.g., encounters
with law enforcement and child welfare
agencies).
Encourage buprenorphine prescribers to make
known their availability if they are prepared to
accept new patients. Help disseminate lists of
addiction treatment providers and share their
information via peer recovery specialists (see
Part 5).
• Rapid assessment and treatment initiation:
Try to help OUD medication providers, partic-
ularly in OTPs, streamline counseling intake
processes to help patients receive medication
effciently. The expert panel of this TIP recog-
nizes that same-day admission of patients with
OUD may not be possible in all settings, but
it’s a worthwhile goal. Every program should
streamline its intake processes and expedite
admissions.
• Return to treatment: When patients dis-
continue treatment prematurely and return
to use of opioids, it can be hard for them to
reengage in treatment because of the shame
they feel or because there is a waiting list
for admission. The waitlist problem may not
be solvable because of capacity limitations,
but all collaborative care team members—
including counselors and prescribers—should:
− Inform patients from intake onward that
the program will readmit them even if they
drop out.
− Encourage patients to seek readmission if
they return to opioid use or feel that they
are at risk for returning to opioid use.
− Inform patients of the importance of
overdose prevention (see the “Counseling
Patients on Overdose Prevention and
Treatment” section).
− Provide continued monitoring if possible; it
can range from informal quarterly check-ins
to regularly scheduled remote counseling or
peer support (e.g., from a recovery coach).
− Offer an expedited reentry process to
encourage patients to return if they need to.
− Engage in active outreach and reengage-
ment with OTP patients, which can be
effective.138,139 Try to contact patients who
have dropped out to encourage them to
return.
Creation of a Supportive
Counseling Experience
Maintaining the Therapeutic Alliance
The therapeutic alliance is a counselor’s most
powerful tool for infuencing outcomes.140
It underlies all types and modalities of therapy
and helping services. A strong alliance welcomes
patients into treatment and creates a sense of
safety.
4-21
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
COUNSELING PATIENTS WITH OUD WHO DON’T TAKE MEDICATION
Patients who don’t take an OUD medication after withdrawal are at high risk of return to opioid use, which
can be fatal given the loss of opioid tolerance. Provide these patients with overdose prevention education
and the overdose-reversal medication naloxone, or educate them about naloxone and how they can
obtain it in their community. Advise them to report a return to opioid use or a feeling that they are at risk
of relapsing. Work with them and their care team to either resume medication for OUD or enter a more
intensive level of behavioral care.
Certain counselor skills help build and
maintain a therapeutic alliance, including:
• Projecting empathy and warmth.
• Making patients feel respected and
understood.
• Not allowing personal opinions, anecdotes, or
feelings to infuence the counseling process
(unless done deliberately and with therapeutic
intention).141
These skills are relevant for working with all
patients, including those taking medication for
OUD. Apply them consistently from the very frst
interaction with a patient through the conclusion
of services. For example, recognize and reconcile
personal views about medication for OUD so
that they don’t infuence counseling sessions.
Educating Patients About OUD and a
Chronic Care Approach to Its Treatment
Help ensure that patients understand the
chronic care approach to OUD and their:
• Diagnosis.
• Prognosis.
• Treatment options.
• Available recovery supports.
• Prescribed medications.
• Risk of overdose (and strategies to reduce it).
Seek to understand patients’ preferences and
goals. Doing so can help convey information
meaningfully so patients understand the choices
available to them. Also, help communicate
patients’ preferences and goals to healthcare
professionals and family members.
Educate colleagues and other staff members
so they can help create a supportive experience
for patients with OUD:
• Provide basic education to colleagues about
medications for OUD and how they work.
• Share evidence on how these medications
reduce risky behavior, improve outcomes, and
save lives.
• Note that major U.S. and international guide-
lines affrm use of medication to treat OUD.
• Ask about and address specifc fears and
concerns.
• Provide resources for additional information.
Counseling Patients on Overdose
Prevention and Treatment
Know how to use naloxone to treat opioid
overdose; share this information with
patients and their family members and
friends. Available by prescription (or without
a prescription in some states), naloxone is an
opioid antagonist that has successfully reversed
many thousands of opioid overdoses. It comes
in auto-injector and nasal spray formulations
easy for laypeople to administer immediately
on the scene of an overdose, before emergency
responders arrive.
Ask patients if they have a naloxone pre-
scription or help them get it without one if
possible. Providers may prescribe naloxone in
addition to OUD medication. Counselors should
check state laws to learn their jurisdiction’s
naloxone prescription and dispensation policies
(see “Resource Alert: Overdose Prevention/
Treatment”).
4-22
Medications for Opioid Use Disorder TIP 63
Inform clients and their friends and families of
any Good Samaritan laws in the jurisdiction,
which protect against drug offenses for people
who call for medical help while experiencing or
observing overdose.
Emphasize that a person given naloxone to
reverse overdose must go to the emergency
department, because overdose can start again
when naloxone wears off.
Consider working with the program admin-
istrator to place a naloxone rescue kit in the
offce, if one is not already available. To be ready
for an emergency, learn:
• The signs of overmedication (which may
progress to overdose) and overdose itself.
• What to do if an overdose is suspected.
• How to administer naloxone.
Consider working with the program admin-
istrators to set up a program to distribute
naloxone directly to patients. Many states
allow organizations to do this under a standing
RESOURCE ALERT
Overdose Prevention/Treatment
SAMHSA Opioid Overdose Prevention Toolkit
(https://store.samhsa.gov/product/Opioid-
Overdose-Prevention-Toolkit/SMA18-4742)
National Conference of State Legislatures’ Drug
Overdose Immunity and Good Samaritan Laws
(www.ncsl.org/research/civil-and-criminal
-justice/drug-overdose-immunity-good
-samaritan-laws.aspx)
Project Lazarus’ Naloxone: The Overdose
Antidote (www.projectlazarus.org/naloxone)
Prescription Drug Abuse Policy System’s:
Interactive Map of Naloxone Overdose
Prevention Laws (http://pdaps.org/datasets
/laws-regulating-administration-of
-naloxone-1501695139)
order from a physician. Clients are more likely
to access naloxone if their program provides it
directly to them rather than sending them to
another organization to get it. Learn more at
Prescribe to Prevent (http://prescribetoprevent.org).
Helping Patients Cope With Bias and
Discrimination
Patients taking medication for OUD must
deal with people—including family members,
friends, colleagues, employers, and community
members—who are misinformed or biased about
the nature of OUD and effective treatments for it
(Exhibit 4.8).
Wherever possible, such as in a counseling
session or a community education forum,
counter misunderstandings with accurate
information. Emphasize the message that
addiction is governed by more powerful brain
forces than those that determine habits. As a
result, having a lot of positive intent, wanting to
quit, and working hard at it sometimes won’t be
enough.
Remind patients about building recovery
capital and sticking with their treatment plan
and goals. A particularly good opportunity to
do so arises when patients ask how to “get off
medication.” Statements such as “The longer
you take medication, the more of your life you
can get back and the less likely you are to return
to opioid use” and “We usually recommend
continuing medication long term because it
helps people maintain recovery” can help clients
understand that they are following medical rec-
ommendations and doing a good job of caring
for themselves (Exhibit 4.9).
People may think that addiction is just
a bad habit or willful self-destruction
and that someone who has diffculty
stopping opioid misuse is lazy. They
may view OUD medication as “just
another drug” and urge patients to
stop taking it.
4-23
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.8. Conversation: Addressing Misinformation
Mother of Patient: They want to put my son on methadone, but it’s going to rot his teeth.
Father of Patient: Yeah. I don’t want him to look like he’s on drugs when he’s fnally off them.
Counselor: You have the impression that people who use drugs have bad teeth. And in many
cases, that’s true. But there are a lot of reasons why people with a substance
use disorder develop teeth and gum problems—such as a high-sugar diet, co-
occurring depression that prevents them from taking good care of themselves,
poor health that allows oral disease to develop, and lack of access to preventive
dental care or treatment. But if your son practices good oral hygiene, his mouth
will stay healthy while he takes methadone.
Mother of Patient: What do you mean by “oral hygiene”?
Counselor: Like all of us, he’ll have to limit his sweets and brush and foss regularly.
Methadone can reduce the fow of saliva, which means that not as much of the
bacteria on his teeth will get washed away. So, he’ll want to get good dental
advice on how to address dry mouth if that’s a problem for him. Regular dental
checkups will be really important, too.
Father of Patient: So, he won’t trade his teeth for his recovery. Thanks—that’s one less thing to worry
about!
Review a client’s motivation for tapering or
quitting medication (Exhibit 4.10) and have a
conversation about the best timing for such a
change (Exhibit 4.11). If the client has consented
to communication with other providers, inform
the client’s prescriber about the client’s desires
or intent so that shared decision making can take
place.
Be proactive in dispelling myths and providing
facts about medications for OUD when coun-
tering misconceptions and judgmental attitudes.
Point out that multiple organizations consider
individuals to be in recovery if they take OUD
medication as prescribed, including:
• The American Medical Association.142
• The American Society of Addiction Medicine.143
• The National Institute on Drug Abuse.144
• The Offce of the Surgeon General.145
• The World Health Organization.146
Explain that alcohol and opioids are different
substances with different effects on the
body and brain. This counters the mistaken
belief that people receiving buprenorphine or
methadone are always “high” and as impaired
as if they drank alcohol all day. People acquire
tolerance to impairments that drinking causes in
motor control and cognition. But this tolerance
is partial; alcohol consumption always results in
some defcits. Opioids don’t have the same motor
or cognitive effects. Complete tolerance develops
to the psychoactive effects and related motor
impairments opioids cause.
If a person takes a therapeutic dose of opioid
agonist medication as prescribed, he or she
may be as capable as anyone else of driving,
being emotionally open, and working produc-
tively. Some people worry that OUD medication
causes a “high” because they’ve seen patients
taking OUD medication whose behavior was
affected by other substances (e.g., benzodiaze-
pines). Others may assume that someone is high
4-24
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.9. Addressing the Misconception That an Opioid Medication
Is “Just Another Drug”
Concerned Colleague: These patients are just replacing one drug with another. Instead of heroin, they’re
using buprenorphine or methadone.
Counselor: Actually, there’s substantial research that medication for opioid use disorder
helps patients stop feeling withdrawal and craving and allows them to get their
life back on track. These medications keep patients in treatment and reduce
crime and HIV risk behavior.
Concerned Colleague: Yeah, but aren’t they still addicted?
Counselor: Physically dependent, yes; but addicted, no. There’s an important difference.
Someone addicted to heroin has to take the drug several times a day to avoid
withdrawal. This usually leads to craving, loss of control, and taking more than
intended. Drug-seeking behavior causes loss of family and friends. It makes the
person unable to perform daily roles and meet obligations.
Concerned Colleague: Yes, I know how addiction works. But isn’t taking methadone an addiction, too?
Counselor: Patients only take methadone once a day, and its makeup is different from
heroin. Daily methadone lets the body stabilize so patients don’t have the highs
and lows that come from heroin use. If patients use heroin, the methadone
blocks its effects; they don’t get high. Methadone is taken orally, so there isn’t the
same danger of infection that comes with injection drug use. Taking methadone
as part of a treatment program lets patients feel normal and focus on changing
the other aspects of their lives that led to drug use.
Concerned Colleague: But you just said they take methadone every day.
Counselor: Yes. That is true of most medications for any disease, if you think about it. Patients
have a physical dependence on the medication but are in remission from addiction.
on a medication for OUD who isn’t taking any
such medication at all.
Point out that many thousands of people are
prescribed medication for OUD every year,
are receiving appropriate treatment, and are
indistinguishable from other people. People
taking OUD medication rely on it to maintain
daily function, like people with diabetes rely
on insulin. Nevertheless, some people think that
individuals taking buprenorphine or methadone
are still addicted to opioids (Exhibit 4.9), even
if they don’t use illicit drugs. For people with
OUD, the medication addresses the compulsion
and craving to use. It also blocks the euphoric
effects of illicit opioids, which over time helps
people stop attempting to use. For people with
EXHIBIT 4.10. When a Patient
Wants To Taper Medication or
Stop Altogether
• Review the decision with the patient to
determine the motivation for tapering or
quitting medication and the best timing for
such a change.
• Tell the prescriber that the patient wants to
taper; shared decision making should guide
the patient’s decision.
• Avoid encouraging tapering, which can imply
that recovery can only truly occur off of the
medication.
4-25
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.11. Responding to a Patient’s Desire To Taper Medication
for OUD
Patient: I want to taper off the buprenorphine.
Counselor: You’d like to taper—can you tell me why?
Patient: I’m getting married. I want a fresh start.
Counselor: You’re saying you’d like to have this all behind you for the new phase in your life.
Patient: Yeah, that’s it.
Counselor: Would it be alright if I share my concerns about that?
Patient: Okay.
Counselor: A big change—whether it’s having a baby, getting a new job, or getting married like
you’re about to do—can be very exciting. But it can also be surprisingly stressful. You
may want to consider staying on the medication during this transition to make sure you
maintain your recovery. I’m just suggesting postponing a taper decision until you start
getting settled into married life.
Patient: I hear you. The last thing I want to do is mess up my marriage right away by using again.
It would be inappropriate for a medical
team to refuse radiation for cancer
patients because the team believes
chemotherapy is always needed, or to
refuse chemotherapy because they
believe that radiation is always needed,
regardless of each patient’s diagnosis
and condition. It would be just as
inappropriate to refuse evidence-
based treatment with medication for
a patient with OUD, when that may be
the most clinically appropriate course
of treatment.
diabetes, medication addresses the problems
caused by inadequate production of insulin by
the pancreas. Medication allows both popula-
tions to live life more fully.
Focus on common ground—all patients want
a healthy recovery, and judging or isolating
someone for return to use doesn’t aid
anyone’s recovery. A divide may occur between
patients in a group setting over return to opioid
use. People in the OUD community typically are
forgiving of return to opioid use and recognize
that it can occur on the path to long-term
recovery. However, some people in mutual-help
communities judge those who return to use (see
the “Helping Clients Find Accepting Mutual-Help
Groups” section). Address judgmental attitudes
through this analogy: People with diabetes whose
blood sugar spikes aren’t condemned and ejected
from treatment.
Dispel the myth that OUD medications make
people sick. In fact, methadone and buprenor-
phine relieve opioid withdrawal, even if patients
don’t feel complete relief in the frst few days.
Taking naltrexone too soon after opioid use
can cause opioid withdrawal, but withdrawal
symptoms can generally be managed success-
fully. Point out that people taking medication
for OUD sometimes get colds, the fu, or other
illnesses, like everyone else. A similar misconcep-
tion is that OUD medications make all patients
sleepy. Exhibit 4.12 offers a sample dialog for
responding to this misconception.
4-26
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.12. Conversation: Redirecting a Concern to the Prescriber
Concerned Colleague: A patient in my group was falling asleep. I think his methadone dose is too high.
Counselor: That’s an important observation. That certainly is possible, although there are
many other possible explanations. What makes you think it’s the medication and
not lack of sleep or some other reason?
Concerned Colleague: Because everyone taking methadone falls asleep in group.
Counselor: Our medical staff members work hard to make sure that each patient is on the
right dose. If a patient is falling asleep in group, you should alert the patient’s
physician right away, regardless of what medication they’re taking. But I’m
wondering if anything besides medication could be causing this issue.
Concerned Colleague: Well, this patient is struggling with having an all-night job.
Counselor: It may be helpful to talk to the patient about moving to a group that meets at
a time when he can be more rested. In any case, to be safe, you should call the
patient’s prescriber about reassessing him.
When return to opioid use comes up in a group
counseling setting, messages about getting back
on track and avoiding shaming and blaming
apply just as much to the patients taking OUD
medication as to other participants. This topic
is an opportunity to address the dangers of
overdose, especially the dangers of using
an opioid after a period of abstinence or
together with other CNS depressants.
Helping Patients Advocate for
Themselves
Educate clients so they can advocate for their
treatment and personal needs. Key topics
include:
• Addiction as a chronic disease infuenced by
genetics and environment.
• The ways that medications for OUD work.
• The process of dose stabilization.
• The benefts of longer term medication use
and risks of abrupt treatment termination.
• The role of recovery supports (e.g., mutual-
help groups) in helping achieve goals.
family and friends know how important they are
and how valuable their support is. Also urge
patients to ask loved ones to help them express
concerns or fears.
Role-playing can help patients self-advocate.
It allows them to practice what to say, what
reactions to expect, and ways to respond. Coach
patients in active listening and in focusing on
solutions rather than problems. Exhibit 4.13
gives an example of a counselor helping a client
self-advocate.
Urge patients to advocate for themselves
beyond one-on-one conversations. Options
include sharing educational pamphlets, inviting
loved ones to a counseling session, or referring
them to websites.
Addressing Discrimination Against
Clients Who Take OUD Medication
Patients can face discriminatory actions
when dealing with individuals, organizations,
or systems that make decisions based on mis-
information about, or biases against, the use
of medication for OUD. The following sectionsOffer clients’ family and friends education on
highlight issues patients taking OUD medicationthese topics, as well, so that they can advocate
may face and how counselors can help.for their loved ones. Encourage patients to let
4-27
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
EXHIBIT 4.13. Conversation: Helping a Client Self-Advocate
Patient: My mom is driving me to my back surgery. I’m worried that she’ll fnd out I’m taking
buprenorphine.
Counselor: It sounds like you’re worried she’ll reject you and be upset if she knows you’re taking
medication.
Patient: I think she’ll be disappointed in me. She thinks people who take addiction medication
are still on drugs.
Counselor: What would you think about fnding a time before your surgery to tell your mother that
you’re taking buprenorphine? You can explain how it works and remind her how well
you’ve been doing maintaining your job, regaining custody of your children, and living
a balanced and healthy life. That may help ease her fears.
Patient: Thanks. I’ll give that a try.
Counselor: If you want, you could invite her to one of our sessions so that I can answer any questions
she has.
Patient: Yeah, she may hear it better from you. I like the idea of having her come in after I’ve told her.
Counselor: When would be a good time to bring up this topic?
Patient: She’s driving me to my pre-op appointment on Friday. Maybe I’ll suggest we go for
coffee after.
Counselor: That’s a good idea. How about we practice that conversation? I’ll play the role of your mom.
Help clients address employment-
related issues
Under the Americans With Disabilities Act,
employers cannot discriminate against
patients taking medication for OUD.147
However, the law doesn’t always stop employers
from taking such action. For example, some
employers conduct workplace urine drug
testing, either before offering employment
or randomly during employment. The OUD
medication they test for most frequently is
methadone, but it’s possible to test for bu-
prenorphine. Naltrexone is generally not tested
for. The TIP expert panel concludes, based on
multiple patient experiences, that patients who
take OUD medication fnd it intimidating to
explain to their employers why their urine test
results are positive for opioids. Yet if they offer
no explanation, they don’t get the callback for
the job or are let go from the job they have.
Direct patients to legal resources and help
them consider how to respond to discrimina-
tion at work based on misinterpreted drug
tests. Offer to speak with their prospective/
current employers to address concerns and
misperceptions about OUD medication and its
effect on their ability to do work tasks.
RESOURCE ALERT
Becoming a Certifed Medication-
Assisted Treatment Advocate
The National Alliance for Medication Assisted
Recovery has a training and credentialing
program for interested people—not just those
who receive medication for OUD—to become
Certifed Medication-Assisted Treatment
Advocates (www.methadone.org/certifcation
/faq.html).
4-28
Medications for Opioid Use Disorder TIP 63
Understand potential legal issues
This section describes issues that can affect access
to care for patients involved in the justice system
who take buprenorphine or methadone for OUD.
These issues usually don’t apply for naltrexone.
Many jails (short term) and prisons (long term)
restrict or disallow access to OUD medication
despite the federal mandate that people who are
incarcerated have access to medical care.148,149
For example:
• A jail may not continue methadone treatment
or allow methadone delivery by patients’ OTPs.
• Patients’ medication may be seized upon arrest.
• Jail health offcials may deny patients’ bu-
prenorphine prescriptions.
Help negotiate patient access to OUD
medication during incarceration. Negotiating
access to OUD medication can be problematic
and often requires multiple meetings between
care providers and jail staff members to resolve
successfully. Patients taking OUD medication
may be forced to go without medication during
incarceration. This increases their risk for opioid
overdose if they return to use after reentering
the community, given the decreased tolerance
that results from interrupted treatment.
Encourage patients to reengage in treatment
as soon as they’re released. People with OUD
released from prison or jail who don’t take OUD
medication have higher risk of overdose death
during their frst few weeks in the community.
Early after release, they are at very high risk of
overdose, given possible:
• Decrease in opioid tolerance while incarcerated.
• Lack of appropriate OUD therapy while
incarcerated.
• OUD medication initiation right before release.
• Release without coordination or a slot for
community-based treatment.
Patients who aren’t opioid tolerant need a lower
starting dose that prescribers will increase more
slowly than usual. Extended-release injectable
naltrexone can be an effective alternative for these
patients.
OPIOID ADDICTION
is linked with high rates of
ILLEGAL ACTIVITY and
INCARCERATION.150,151
Support patients in getting legal advice or
counsel via their OUD medication prescribers’
healthcare organization. Members of the TIP
expert panel have observed situations in which
law enforcement personnel arrested patients
leaving methadone clinics and charged them
with driving under the infuence or arrested them
after fnding buprenorphine prescription bottles
in their cars. Discussions among treatment orga-
nizations and local law enforcement leadership
can help address such situations.
Address concerns and advocate for addiction
specialists to select treatments best suited
for each patient. Sometimes, authorities insist
that patients enter a particular kind of treatment
or follow particular rules related to their OUD.
To ensure a patient-centered focus, help involve
addiction specialists in determining what kind of
treatment best meets patients’ needs. This kind
of advocacy works best when counselors and the
programs for which they work have preexisting
relationships with personnel in local employ-
ment, law enforcement, drug court, and child
welfare facilities.
Address issues in dealing with healthcare
providers
Misunderstandings about OUD and its
treatment aren’t rare among healthcare
providers:
• Patients admitted to the hospital for medical
issues may face prejudice from hospital staff
members.
• Providers may not know how to manage
patients’ OUD medication during their
hospital stay.
4-29
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
• Some providers don’t know how to manage
pain in someone taking medication for OUD.
Help communicate issues to patients’
prescribers, who can advocate for proper
handling of OUD medication. It is also possible
to help hospital staff members see the patient
as a whole person who deserves respect and to
provide them with essential information about
treatment for OUD.
Inpatient SUD treatment facilities may refuse
admission until patients are off buprenorphine
or methadone. Sometimes, patients taking
OUD medication seek admission to inpatient
facilities for treatment of an additional SUD,
a mental disorder, or both. If a facility won’t
accept someone on OUD medication, call on
local or state regulatory authorities (e.g., the
State Opioid Treatment Authority) and patients’
healthcare professionals to intervene with the
facility’s professional staff and management.
Demonstrate awareness of pregnancy and
parenting issues
Healthcare professionals may be unaware
of current guidelines for treating pregnant
women with OUD (Exhibit 4.14). As a result,
they may inappropriately:
• Deny OUD medication to pregnant women.
• Discourage breastfeeding by mothers taking
OUD medication.
Treatment of Pain in Patients
With OUD
SAMHSA’s TIP 54, Managing Chronic Pain in
Adults With or in Recovery From Substance Use
Disorders (https://store.samhsa.gov/product/TIP
-54-Managing-Chronic-Pain-in-Adults-With-or
-in-Recovery-From-Substance-Use-Disorders
/SMA13-4671)
• Direct women who become pregnant while
taking OUD medication to undergo with-
drawal from their medication and attempt
abstinence.
Hospital policies on screening infants for
prenatal substance exposure vary considerably.
A positive screen may trigger involvement of
Child Protective Services. This may occur even
when the positive screen results from treatment
with OUD medication under a physician’s care
rather than opioid misuse.
Help pregnant and postnatal clients in these
situations by:
• Educating them and encouraging them to
share pertinent information and resources with
healthcare professionals involved in their care.
• Coordinating with their prescribers to help
them get prenatal and postnatal care from
well-informed healthcare professionals.
• Getting involved in efforts to educate
the local healthcare community about
best practices for the care of pregnant and
postnatal women with OUD.
Legal problems can arise if Child Protective
Services or legal personnel don’t understand
that parents receiving OUD medication are
fully capable of caring for children and con-
tributing to their families. Judges, probation
or parole offcers, or Child Protective Services
workers may inappropriately request that patients
discontinue medication as a condition of family
Pregnancy- and Parenting-Related
Issues
SAMHSA’s Clinical Guidance for Treating
Pregnant and Parenting Women With Opioid
Use Disorder and Their Infants (https://store
.samhsa.gov/product/SMA18-5054)
RESOURCE ALERT RESOURCE ALERT
4-30
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.14. Summary of Current Guidance for the Treatment
of Pregnant Women With OUD
• An obstetrician and an addiction treatment provider should comanage care, and the woman should
receive counseling and supportive services as needed to assist her in achieving a stable life.
• Treatment with methadone or buprenorphine without naloxone during pregnancy is recommended.
Treatment with naltrexone is not recommended during pregnancy.
• Medically supervised withdrawal during pregnancy is typically not advisable. If not done with great
care in a controlled setting, it can cause premature labor, fetal distress, and miscarriage. Attempts at
abstinence from opioids without the support of medication are generally not advised because of the
risk of return to opioid use, which can adversely affect both mother and fetus.
• Newborns of women who take OUD medication often show symptoms of NAS, which is treatable. NAS
from opioid agonist treatment is not as harmful to the fetus as continued use of illicit opioids during
pregnancy.
• Mothers stabilized on medication for OUD are encouraged to breastfeed.
Summarized from SAMHSA’s publication A Collaborative Approach to the Treatment of Pregnant
Women With Opioid Use Disorders (https://store.samhsa.gov/product/A-Collaborative-Approach-to
-the-Treatment-of-Pregnant-Women-with-Opioid-Use-Disorders/SMA16-4978).152
reunifcation. Such orders are medically inappro-
priate and should be challenged. Possible ways
to help:
• Write letters to judges and lawyers explaining
how effective OUD medication can be.
• Send judges and lawyers literature about
current medical recommendations (including
this TIP).
• Testify in court, if necessary.
Helping Clients Find Accepting Mutual-
Help Groups
Voluntary participation in 12-Step groups can
improve abstinence and recovery-related skills
and behaviors for some people with SUDs.
Greater involvement (e.g., being a 12-Step
sponsor) can increase these benefts.153,154,155,156
However, not much research has explored less
widespread types of groups (e.g., groups that
follow a given religion’s principles, secular
groups that downplay the spiritual aspects of
12-Step groups). Research exploring longitudinal
outcomes for people with OUD who attend NA
is limited, but fndings link more frequent atten-
dance with abstinence.157,158,159
Clients taking medication for OUD may face
challenges in attending mutual-help groups.
For example:
• NA, the most widely available program, treats
illicit opioids and OUD medications equally in
gauging abstinence and recovery. NA doesn’t
consider people taking OUD medication
“clean and sober.”160
• Local chapters of NA may decide not to allow
people taking OUD medication to participate
at meetings or may limit their participation
(e.g., not allowing service work).
• Clients attending some NA meetings may
encounter hostile attitudes toward the use of
medication.
• AA’s offcial policy is more accepting of the
use of prescribed medication, but clients may
still encounter negative attitudes toward their
use of medications for OUD.
• Other groups, such as some religious mutual-
help programs, SMART Recovery, and LifeRing
Secular Recovery, also have policies that could
challenge clients for taking medication for OUD.
4-31
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
RESOURCE ALERT
Addressing Bias and Discrimination
Are You in Recovery From Alcohol or Drug
Problems? Know Your Rights: Rights for
Individuals on Medication-Assisted Treatment:
SAMHSA publication explaining patient rights
and federal laws that protect people receiving
OUD medication. Describes whom these
laws protect and what they cover, including
employment, housing, services, and public
accommodations (www.samhsa.gov/sites/
default/fles/programs_campaigns/medication_
assisted/Know-Your-Rights-Brochure.pdf)
Medication-Assisted Treatment for Opioid
Addiction: Myths and Facts: Legal Action
Center publication that dispels myths and
provides facts about OUD medication
(www.lac.org/assets/fles/Myth-Fact-for-MAT.
pdf)
Methadone Maintenance Myths and
Resources: Missouri Department of Mental
Health factsheet (https://dmh.mo.gov/media/pdf/
methadone-maintenance-myths-and-resources)
Prepare clients who take medication for
OUD to attend mutual-help meetings
Clients will be better able to fnd supportive
mutual-help groups if their counselor and
program:
• Evaluate attitudes toward medication for
OUD among local mutual-help groups.
• Keep on hand information about all mutual-
help options available in the clients’ area.
• Recruit volunteers from mutual-help groups
to help clients fnd and attend meetings
(e.g., by providing transportation, serving as
“sponsors,” introducing clients).
• Do not mandate meeting attendance.
Recommending participation is just as
effective.161
• Keep track of clients’ experiences at
different groups to ensure that meetings
remain welcoming.
• Help clients start onsite mutual-help
groups.
• Ask staff members to evaluate their own
feelings and beliefs about mutual-help
groups.162
Facilitate positive mutual-help group
experiences
• Educate clients about mutual-help groups.
Explore group types, risks and benefts of
participation, and limitations of research in
support of those risks and benefts.
• Suggest buddying up. Clients can attend
meetings with other people who take medica-
tion for OUD.
• Review with clients their understanding of
and prior experience with mutual help.
• Explore clients’ understanding of the
benefts and risks of disclosure about taking
OUD medication.
• Develop a risk-reduction plan for disclosure
if clients want to share their use of OUD
medication (e.g., talking with an individual
group member instead of disclosing to the
entire group).
• Help clients anticipate and learn to handle
negative responses:
− Develop sample scripts clients can use
when questioned about their medication.
− Role-play scenarios in which clients respond
to questions about their use of medication.
• Respect the privacy of clients’ participation
in mutual-help groups and recognize that
some groups ask that participants not discuss
what occurs in meetings.
4-32
Medications for Opioid Use Disorder TIP 63
• Make sure clients know they can talk about
their experiences in mutual-help groups
but don’t pressure them to disclose in these
groups that they take OUD medication.
• Consider mutual-help participation using
groups more open to OUD medication (e.g.,
attending AA even if the client has no alcohol
use disorder; attending groups for co-
occurring substance use and mental disorders,
such as Dual Recovery Anonymous or Double
Trouble in Recovery). Clients with OUD who
attend AA and not NA have similar recovery-
related outcomes and retention rates.163
RESOURCE ALERT
How To Use Technology-Based
Tools in Behavioral Health Services
SAMHSA’s TIP 60, Using Technology-Based
Therapeutic Tools in Behavioral Health
Services, is available from the SAMHSA Store
(https://store.samhsa.gov/product/TIP-60
-Using-Technology-Based-Therapeutic-Tools
-in-Behavioral-Health-Services/SMA15-4924).
In addition to discussing online mutual-help
groups, this TIP can help counselors implement
technology-assisted care for patients with OUD.
It highlights the importance of using technology-
based assessments and interventions and
discusses how technology reduces barriers to
treatment.
Online mutual-help groups
Before recommending an online group, check
its content and tone on the use of medication.
Mutual help using the Internet (either through
real-time chat rooms or discussion boards
where one posts and waits for responses) has
been growing in popularity. This is an especially
valuable resource for clients living in rural and
remote areas. Groups range from general
meetings for people with a particular SUD (e.g.,
online AA meetings) to those that are very
specifc (e.g., Moms on Methadone). Moderated
groups are preferable to unmoderated groups.
TIP 60, Using Technology-Based Therapeutic
Tools in Behavioral Health Services, addresses
many of the pros and cons of online support
groups.164 Part 5 of this TIP gives links for several
groups that the TIP expert panel has identifed
as helpful.
RESOURCE ALERT
Mutual Help for Clients With OUD
William White’s Narcotics Anonymous and the
Pharmacotherapeutic Treatment of Opioid
Addiction in the United States: Publication
that gives more information on the pros and
cons of 12-Step groups for people receiving
medication for OUD and how to prepare them
for meetings165 (http://atforum.com/documents
/2011NAandMedication-assistedTreatment.pdf)
White, Galanter, Humphreys, and Kelly’s “The
Paucity of Attention to Narcotics Anonymous
in Current Public, Professional, and Policy
Responses to Rising Opioid Addiction”: Peer-
reviewed journal article on the benefts of NA
and the need to include it among the options
offered to people receiving medication for OUD166
(www.tandfonline.com/doi/abs/10.1080/0734732
4.2016.1217712)
4-33
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
Mutual-help groups specifc to OTPs
Although these meetings occur mostly on
the premises of OTPs, it may be possible to
use the models developed by OTPs in more
general SUD treatment settings. Because they
serve only patients receiving medication to treat
OUD, OTPs can create and sustain onsite mutual-
help groups specifc to this population. Such
groups include Methadone Anonymous (MA),167
other variations on a 12-Step model,168,169 and
the mutual-help component of Medication-
Assisted Recovery Services (MARS). MARS is
a recovery community organization, not just a
mutual-help program. MARS members design,
implement, and evaluate a variety of peer-
delivered recovery support services in addition
to providing meetings. More information on
these programs is in the articles cited and online
resources presented in Part 5.
Facilitating Groups That Include Patients
Taking OUD Medication
Foster acceptance via attitude and behavior
when facilitating groups that include patients
taking OUD medication:
• Establish ground rules about being respect-
ful, avoiding negative comments about group
members, and keeping statements made in
the group confdential—as with any group.
• Be proactive. State up front that ground
rules apply to everyone, regardless of a given
person’s decisions about whether to include
OUD medication in his or her path to recovery.
• Ask members to discuss how to address
any negative comments, should they occur.
This is especially important for mixed groups.
• Ask group members to affrm that they will
abide by the rules.
• Provide consistent reminders throughout
each session about the ground rules.
Group members may still make negative
comments about medication for OUD. Avoid
feeding the negativity with attention, which
can worsen the situation. Reframe negative
comments to express underlying motivations,
often based on fear or misunderstanding.
Remain positive; model expected behavior,
which can beneft the person who made the
negative remark (Exhibit 4.15).
Additional tips for leading mixed groups include
the following:
• Treat patients taking OUD medication
the same as other patients in the group.
Patients taking medication can participate
in and beneft from individual and group
counseling just like other patients. There is
no need to have separate counseling tracks
EXHIBIT 4.15. Redirecting Negative Comments
Petra: How can you say Joni is in recovery when she’s still taking a drug every day? I struggled
every day and never took anything for 10 years.
Counselor: I hear your concern for Joni. You want her recovery to follow the same path you took in yours.
Petra: Right! And she’s taking methadone, which is an opioid. People use opioids to get high.
Counselor: In this treatment program, we see addiction as a brain disease. Methadone treats the
brain disease part of addiction. It stabilizes the brain and allows the person to focus on
learning new ways of thinking and reacting. It works by blocking the effects of other
opioids. Patients on a proper dose can’t get high even if they try to use. This helps
discourage future drug use. Joni, would you like to add anything?
Joni: Petra, it’s great that you stopped using opioids and stayed in recovery without
medication—but everyone has a different path to recovery. For me, medication helps me
hold a job, take care of my kids, stay focused in my counseling sessions, and feel normal.
4-34
Medications for Opioid Use Disorder TIP 63
based on OUD medication status, nor should
that status limit a participant’s responsibilities,
leadership role, or level of participation.
• Meet with patients taking OUD medication
in advance to prepare them for mixed-
group settings. Advise them that they don’t
have to disclose their medication status to the
group, just as they don’t have to disclose any
other health issues. Counsel them that if they
choose to talk about their medication status,
it helps to talk about how medication has
helped shape their personal recovery.
• Don’t single out patients taking OUD
medication. Let participants decide whether
to tell the group about any issue they want to
share, including medication status. If a patient
chooses to disclose that status, follow up after
the session to ensure that he or she is in a
positive space and feels supported.
• Keep the session’s focus on the topic and
not on the pros and cons of medication for
OUD. If the person receiving medication for
OUD or other group members have specifc
questions about such medications, have them
ask their healthcare professionals.
• Reinforce messages of acceptance. During
the wrap-up discussion at the end of a
session, members may comment on points
that stood out for them. This is a chance to
restate information accurately and model
respect for each patient’s road to recovery,
whether it includes OUD medication or not.
• Review confdentiality rules. Affrm that
patients’ OUD medication status will not be
shared with other group members. Remind
participants to think carefully before sharing
personal details such as their medication
status with the group, because other partic-
ipants may not respect confdentiality even
if they have agreed to do so as part of the
group guidelines.
Other Common Counseling
Concerns
Patients must sign releases to permit ongoing
conversations between care providers in
accordance with federal regulations on con-
fdentiality of medical records for patients in
treatment for an SUD (42 CFR Part 2). When
patients’ primary care providers, prescribers
of medication for OUD, and addiction-specifc
counselors don’t work for the same entity,
patients must consent for them to share
information.
It can be challenging when a patient refuses
to consent to collaborative communication
among his or her healthcare team members.
In these cases, the professionals involved must
decide whether they will continue to provide
either medication or counseling services without
permission to collaborate. In other words,
is cross-communication among all providers
required for collaborative care? The answer to
this complicated question depends on each
patient’s circumstances.
The TIP expert panel recommends
communication among providers
as the standard of care for OUD
treatment and recovery support.
Carefully consider deviations from this
standard, which should occur only
rarely. That said, individualize decisions
about collaborative communication
among providers to each patient’s
unique preferences, needs, and
circumstances.
4-35
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
Patients may not consent to communication
among providers if they:
• Have experienced discrimination in health-
care systems.
• Have developed OUD after taking opioid
pain medication.
• Have legitimate cause not to trust
providers (e.g., perceiving themselves
as having been abused by a healthcare
professional).170
• Are not ready to make primary care
providers aware of their disorder, even
(or especially) if those providers have been
prescribing opioid pain medication.
• Encounter problems in making progress
toward recovery. After typically consenting
to communication among providers, a
patient’s sudden revocation may signal
trouble in recovery.
Exhibit 4.16 lists common collaborative care
issues and responses counselors can consider.
Suggested responses assume that patients have
consented to open exchange of information
among all providers.
EXHIBIT 4.16. Common Collaborative Care Issues and Possible
Counselor Responses
POTENTIAL MEDICATION-
RELATED ISSUE COUNSELOR RESPONSE
The patient complains of Talk with the patient about his or her medication adherence. Review
continued cravings. with the patient strategies for overcoming cravings using a CBT
model.
Communicate with the prescriber to see whether dosage can be
adjusted to subdue the cravings.
A patient taking methadone Ask the patient whether drowsiness is caused by lack of sleep,
does not appear engaged disturbed sleep, substance use, or overmedication. Consider
in counseling sessions obtaining a spot urine test (if available).
and seems drowsy during
conversations.
In all cases of drowsiness, alert the prescriber immediately so that the
cause can be determined. This is particularly important during the
frst few weeks of treatment.
The patient is at risk for Inform the prescriber if the patient appears at risk for return to use
return to opioid use. given cravings, life stressors, changes in social circumstances, new
triggers, or the like. This alerts the prescriber to monitor the patient
more closely and consider medication changes to reduce likelihood
of return to use.
The patient has recently
returned to opioid misuse
after a period of abstinence.
Gather details about circumstances surrounding the incident of use
and, in collaboration with the prescriber and the patient, adjust the
treatment plan accordingly. Reinforce the patient’s understanding of
the increased risk of opioid overdose given altered levels of tolerance.
Continued on next page
4-36
Medications for Opioid Use Disorder TIP 63
EXHIBIT 4.16. Common Collaborative Care Issues and Possible
Counselor Responses (continued)
POTENTIAL MEDICATION-
RELATED ISSUE COUNSELOR RESPONSE
The patient is discussing Direct the patient to a healthcare professional for assessment of pain
chronic pain with the and medical treatment as necessary.
counselor. If indicated as appropriate by a healthcare professional, provide CBT
for dealing with pain or instruct the patient in adjunct methods for
pain relief (e.g., meditation, exercise, physical therapy).
The patient is asking the Answer questions based on your knowledge of medications for
counselor for medical advice treatment of OUD but don’t provide medical advice. Refer the patient
on what dose to take, side to the prescriber for that.
effects, how long to stay on
the medication, and the like.
As appropriate, contact the prescriber with the patient to have a
three-way discussion.
The counselor or patient
is concerned that the
prescriber is not giving
quality care.
As appropriate, advocate for the patient with the prescribing medical
team.
The patient discloses use of Use motivational interviewing techniques to have a collaborative
other drugs. conversation about the details of this drug use. For example, give a
response like “Tell me more about this,” followed by questions about
the specifc drugs used, why they were used, and what the patient’s
thoughts are about changing that drug use.
The patient discloses that Advise the patient to contact her prescriber immediately no matter
she is pregnant. what medication she is taking. Work with her to help her get access
to prenatal care (if she doesn’t have it already) and other health
services related to pregnancy as needed.
The patient has a positive Using motivational interviewing tools, discuss with the patient the
urine screen. context of the substance use and what implications this use may
have for the treatment plan. If the patient denies the substance use,
reconsider the patient’s readiness to change and how it affects the
treatment plan.
4-37
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
Notes
1 Centers for Disease Control and Prevention. (2016).
Increases in drug and opioid-involved overdose deaths—
United States, 2010–2015. Morbidity and Mortality
Weekly Report, 65(50–51),1445–1452.
2 Center for Behavioral Health Statistics and Quality. (2020).
Results from the 2019 National Survey on Drug Use and
Health: Detailed tables. Rockville, MD: Substance Abuse
and Mental Health Services Administration. Retrieved
April 28, 2021, from www.samhsa.gov/data/
3 American Society of Addiction Medicine. (2011).
Defnition of addiction. Retrieved October 30, 2017, from
www.asam.org/resources/defnition-of-addiction
4 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
5 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
6 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
7 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Association.
8 National Cancer Institute. (n.d.). Remission. In NCI
dictionary of cancer terms. Retrieved November 22,
2017, from www.cancer.gov/publications/dictionaries
/cancer-terms?cdrid=45867
9 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
10 Manchikanti, L. (2007). National drug control policy
and prescription drug abuse: Facts and fallacies. Pain
Physician, 10, 399–424.
11 Jones, C. M. (2013). Heroin use and heroin use risk
behaviors among nonmedical users of prescription opioid
pain relievers—United States, 2002–2004 and 2008–2010.
Drug and Alcohol Dependence, 132(1–2), 95–100.
12 Hedegaard, H., Chen, L. H, & Warner, M. (2015).
Drug-poisoning deaths involving heroin: United States,
2000–2013. NCHS Data Brief, No. 190. Hyattsville, MD:
National Center for Health Statistics.
13 Centers for Disease Control and Prevention. (2016).
Increases in drug and opioid-involved overdose deaths—
United States, 2010–2015. Morbidity and Mortality
Weekly Report, 65(50–51),1445–1452.
14 Substance Abuse and Mental Health Services
Administration. (n.d.). Opioid treatment program
directory. Retrieved October 19, 2017, from https://dpt2.
samhsa.gov/treatment/directory.aspx
15 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
16 Carroll, K. M., & Weiss, R. D. (2016). The role of
behavioral interventions in buprenorphine maintenance
treatment: A review. American Journal of Psychiatry,
174(8), 738–747.
17 McLellan, A. T., Lewis, D. C., O’Brien, C. P., & Kleber, H.
D. (2000). Drug dependence, a chronic medical illness:
Implications for treatment, insurance, and outcomes
evaluation. JAMA, 284(13), 1689–1695.
18 Connery, H. S. (2015). Medication-assisted treatment of
opioid use disorder: Review of the evidence and future
directions. Harvard Review of Psychiatry, 23(2), 63–75.
19 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., ... Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
20 Thomas, C. P., Fullerton, C. A., Kim, M., Montejano,
L., Lyman, D. R., Dougherty, R. H., ... Delphin-Rittman,
M. E. (2014). Medication-assisted treatment with
buprenorphine: Assessing the evidence. Psychiatric
Services, 65(2), 158–170.
21 American Society of Addiction Medicine. (2015).
The ASAM national practice guideline for the use of
medications in the treatment of addiction involving
opioid use. Chevy Chase, MD: Author.
22 Sordo, L., Barrio, G., Bravo, M. J., Indave, B. I.,
Degenhardt, L., Wiessing, L., ... Pastor-Barriuso, R.
(2017). Mortality risk during and after opioid substitution
treatment: Systematic review and meta-analysis of cohort
studies. British Medical Journal (Clinical Research Ed.),
357, j1550.
23 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
24 Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède,
J. P., & Tignol, J. (2004). French feld experience with
buprenorphine. American Journal on Addictions,
13(Suppl. 1), S17–S28.
25 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., &
Burns, L. (2009). Mortality among clients of a state-wide
opioid pharmacotherapy program over 20 years: Risk
factors and lives saved. Drug and Alcohol Dependence,
105(1–2), 9–15.
4-38
Medications for Opioid Use Disorder TIP 63
26 Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
27 Merlo, L. J., Greene, W. M., & Pomm, R. (2011).
Mandatory naltrexone treatment prevents relapse among
opiate-dependent anesthesiologists returning to practice.
Journal of Addiction Medicine, 5(4), 279–283.
28 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(4), 1–45.
29 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., ... Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
30 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
31 Kresina, T. F., & Lubran, R. (2011). Improving public
health through access to and utilization of medication
assisted treatment. International Journal of Environmental
Research and Public Health, 8(10), 4102–4117.
32 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A.,
Gastfend, D. R., & Silverman, B. L. (2011). Injectable
extended-release naltrexone for opioid dependence:
A double-blind, placebo-controlled, multicentre
randomized trial. Lancet, 377(9776), 1506–1533.
33 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
34 Timko, C., Schultz, N. R., Cucciare, M. A., Vittorio, L.,
& Garrison-Diehn, C. (2016). Retention in medication-
assisted treatment for opiate dependence: A systematic
review. Journal of Addictive Diseases, 35(1), 22–35.
35 Fiellin, D. A., Schottenfeld, R. S., Cutter, C. J., Moore, B.
A., Barry, D. T., & O’Connor, P. G. (2014). Primary care-
based buprenorphine taper vs maintenance therapy for
prescription opioid dependence: A randomized clinical
trial. JAMA Internal Medicine, 174(12), 1947–1954.
36 Kakko, J., Svanborg, K. D., Kreek, M. J., & Heilig,
M. (2003). 1-year retention and social function after
buprenorphine-assisted relapse prevention treatment for
heroin dependence in Sweden: A randomised, placebo-
controlled trial. Lancet, 361(9358), 662–668.
37 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., ... Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence: A
randomized controlled trial. JAMA, 283(10), 1303–1310.
38 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., ... Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
39 Amato, L., Davoli, M., Minozzi, S., Ferroni, E., Ali, R., &
Ferri, M. (2013). Methadone at tapered doses for the
management of opioid withdrawal. Cochrane Database
of Systematic Reviews, 2013(2), 1–68.
40 Bart, G. (2012). Maintenance medication for opiate
addiction: The foundation of recovery. Journal of
Addictive Diseases, 31(3), 207–225.
41 Fiellin, D. A., Schottenfeld, R. S., Cutter, C. J., Moore, B.
A., Barry, D. T., & O’Connor, P. G. (2014). Primary care-
based buprenorphine taper vs maintenance therapy for
prescription opioid dependence: A randomized clinical
trial. JAMA Internal Medicine, 174(12), 1947–1954.
42 White, W. L. (2012). Medication-assisted recovery
from opioid addiction: Historical and contemporary
perspectives. Journal of Addictive Diseases, 31(3),
199–206.
43 Substance Abuse and Mental Health Services
Administration. (1999). Enhancing motivation for change
in substance abuse treatment. Treatment Improvement
Protocol (TIP) Series 35. HHS Publication No. (SMA)
13-4212. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
44 McHugh, R. K., Hearon, B. A., & Otto, M. W. (2010).
Cognitive behavioral therapy for substance use disorders.
Psychiatric Clinics of North America, 33(3), 511–525.
45 Ling, W., Hillhouse, M., Ang, A., Jenkins, J., & Fahey, J.
(2013). Comparison of behavioral treatment conditions
in buprenorphine maintenance. Addiction, 108(10),
1788–1798.
46 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J.,
Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S.
(2013). A randomized trial of cognitive behavioral therapy
in primary care-based buprenorphine. American Journal
of Medicine, 126(1), 74.e11– 74.e17.
47 Moore, B. A., Fiellin, D. A., Cutter, C. J., Biondo, F. D.,
Barry, D. C., Fiellin, L. E., … Schottenfeld, R. S. (2016).
Cognitive behavioral therapy improves treatment
outcomes for prescription opioid users in primary care
buprenorphine treatment. Journal of Substance Abuse
Treatment, 71, 54–57.
48 Abbott, P. J. (2010). Case management: Ongoing
evaluation of patients’ needs in an opioid treatment
program. Professional Case Management, 15(3), 145–152.
4-39
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
49 Morgenstern, J., Neighbors, C. J., Kermis, A., Riordan,
A., Blanchard, K. A., McVeigh, K. H., ... McCredie, B.
(2009). Improving 24-month abstinence and employment
outcomes for substance-dependent women receiving
temporary assistance for needy families with intensive
case management. American Journal of Public Health,
99(2), 328–333.
50 Substance Abuse and Mental Health Services
Administration. (2000). Comprehensive case management
for substance abuse treatment. Treatment Improvement
Protocol (TIP) Series 27. HHS Publication No. (SMA)
15-4215. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
51 National Institute on Drug Abuse. (2012). Principles
of drug addiction treatment: A research-based guide
(3rd ed.). NIH Publication No. 12–4180. Bethesda, MD:
Author.
52 Woo, J., Bhalerao, A., Bawor, M., Bhatt, M., Dennis, B.,
Mouravska, N., … Samaan, Z. (2017). “Don’t judge a
book by its cover”: A qualitative study of methadone
patients’ experiences of stigma. Substance Abuse:
Research and Treatment, 11, 1–12.
53 Dugosh, K., Abraham, A., Seymour, B., McLoyd, K.,
Chalk, M., & Festinger, D. (2016). A systematic review
on the use of psychosocial interventions in conjunction
with medications for the treatment of opioid addiction.
Journal of Addiction Medicine, 10(2), 93–103.
54 Roberts, J., Annett, H., & Hickman, M. (2011). A
systematic review of interventions to increase the uptake
of opiate substitution therapy in injecting drug users.
Journal of Public Health, 33(3), 378–384.
55 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J.,
Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S.
(2013). A randomized trial of cognitive behavioral therapy
in primary care-based buprenorphine. American Journal
of Medicine, 126(1), 74.e11–74.e17.
56 Ling, W., Hillhouse, M., Ang, A., Jenkins, J., & Fahey, J.
(2013). Comparison of behavioral treatment conditions
in buprenorphine maintenance. Addiction, 108(10),
1788–1798.
57 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., ... Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
58 Ling, W., Hillhouse, M., Ang, A., Jenkins, J., & Fahey, J.
(2013). Comparison of behavioral treatment conditions
in buprenorphine maintenance. Addiction, 108(10),
1788–1798.
59 National Institute on Drug Abuse. (2012). Principles
of drug addiction treatment: A research-based guide
(3rd ed.). NIH Publication No. 12–4180. Bethesda, MD:
Author.
60 Weiss, R. D., Griffn, M. L., Potter, J. S., Dodd, D. R.,
Dreifuss, J. A., Connery, H. S., & Carroll, K. M. (2014).
Who benefts from additional drug counseling among
prescription opioid-dependent patients receiving
buprenorphine-naloxone and standard medical
management? Drug and Alcohol Dependence, 140,
118–122.
61 Connock, M., Juarez-Garcia, A., Jowett, S., Frew, E.,
Liu, Z., Taylor, R. J., … Taylor, R. S. (2007). Methadone
and buprenorphine for the management of opioid
dependence: A systematic review and economic
evaluation. Health Technology Assessment, 11(9), 1–171,
iii–iv.
62 De Maeyer, J., Vanderplasschen, W., & Broekaert,
E. (2010). Quality of life among opiate-dependent
individuals: A review of the literature. International
Journal on Drug Policy, 21(5), 364–380.
63 Carpentier, P. J., Krabbe, P. F., van Gogh, M. T., Knapen,
L. J., Buitelaar, J. K., & de Jong, C. A. (2009). Psychiatric
comorbidity reduces quality of life in chronic methadone
maintained patients. American Journal on Addictions,
18(6), 470–480.
64 Muller, A. E., Skurtveit, S., & Clausen, T. (2016). Many
correlates of poor quality of life among substance users
entering treatment are not addiction-specifc. Health and
Quality of Life Outcomes, 14, 1–10.
65 De Maeyer, J., Vanderplasschen, W., & Broekaert,
E. (2010). Quality of life among opiate-dependent
individuals: A review of the literature. International
Journal on Drug Policy, 21(5), 364–380.
66 Carpentier, P. J., Krabbe, P. F., van Gogh, M. T., Knapen,
L. J., Buitelaar, J. K., & de Jong, C. A. (2009). Psychiatric
comorbidity reduces quality of life in chronic methadone
maintained patients. American Journal on Addictions,
18(6), 470–480.
67 Fei, J. T. B., Yee, A., Habil, M. H. B., & Danaee, M. (2016).
Effectiveness of methadone maintenance therapy and
improvement in quality of life following a decade of
implementation. Journal of Substance Abuse Treatment,
69, 50–56.
68 Millson, P., Challacombe, L., Villeneuve, P. J., Strike, C. J.,
Fischer, B., Myers, T., ... Hopkins, S. (2006). Determinants
of health-related quality of life of opiate users at entry to
low-threshold methadone programs. European Addiction
Research, 12(2), 74–82.
69 Krebs, E., Kerr, T., Wood, E., & Nosyk, B. (2016).
Characterizing long-term health related quality of life
trajectories of individuals with opioid use disorder.
Journal of Substance Abuse Treatment, 67, 30–37.
70 Millson, P., Challacombe, L., Villeneuve, P. J., Strike, C. J.,
Fischer, B., Myers, T., … Hopkins, S. (2006). Determinants
of health-related quality of life of opiate users at entry to
low-threshold methadone programs. European Addiction
Research, 12(2), 74–82.
4-40
Medications for Opioid Use Disorder TIP 63
71 De Maeyer, J., Vanderplasschen, W., & Broekaert,
E. (2010). Quality of life among opiate-dependent
individuals: A review of the literature. International
Journal on Drug Policy, 21(5), 364–380.
72 Muller, A. E., Skurtveit, S., & Clausen, T. (2016). Many
correlates of poor quality of life among substance users
entering treatment are not addiction-specifc. Health and
Quality of Life Outcomes, 14, 1–10.
73 Cavaiola, A. A., Fulmer, B. A., & Stout, D. (2015). The
impact of social support and attachment style on quality
of life and readiness to change in a sample of individuals
receiving medication-assisted treatment for opioid
dependence. Substance Abuse, 36(2), 183–191.
74 Millson, P., Challacombe, L., Villeneuve, P. J., Strike, C. J.,
Fischer, B., Myers, T., … Hopkins, S. (2006). Determinants
of health-related quality of life of opiate users at entry to
low-threshold methadone programs. European Addiction
Research, 12(2), 74–82.
75 Center for Substance Abuse Treatment. (2007). National
Summit on Recovery: Conference report. HHS Publication
No. (SMA) 07–4276. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
76 Substance Abuse and Mental Health Services
Administration. (2012). SAMHSA’s working defnition
of recovery. Retrieved November 24, 2017,
from https://store.samhsa.gov/product/
SAMHSA-s-Working-Defnition-of-Recovery/
PEP12-RECDEF
77 Jackson, L. A., Buxton, J. A., Dingwell, J., Dykeman, M.,
Gahagan, J., Gallant, K., … Davison, C. (2014). Improving
psychosocial health and employment outcomes for
individuals receiving methadone treatment: A realist
synthesis of what makes interventions work. BMC
Psychology, 2, 1–20.
78 Kaplan, L. (2008). The role of recovery support services
in recovery-oriented systems of care. HHS Publication
No. (SMA) 08-4315. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
79 White, W. L., & Mojer-Torres, L. (2010). Recovery-oriented
methadone maintenance. Retrieved October 23, 2017,
from www.williamwhitepapers.com/pr/2011%20Bamber-
White%20Dialogue%20on%20Recovery-Oriented%20
Methadone%20Maintenace.pdf
80 Hser, Y. I. (2007). Predicting long-term stable recovery
from heroin addiction: Findings from a 33-year follow-up
study. Journal of Addictive Diseases, 26(1), 51–60.
81 Laudet, A. B., & White, W. L. (2008). Recovery capital
as prospective predictor of sustained recovery, life
satisfaction, and stress among former poly-substance
users. Substance Use and Misuse, 43(1), 27–54.
82 Skinner, M. L., Haggerty, K. P., Fleming, C. B., Catalano,
R. F., & Gainey, R. R. (2011). Opiate-addicted parents in
methadone treatment: Long-term recovery, health, and
family relationships. Journal of Addictive Diseases, 30(1),
17–26.
83 Substance Abuse and Mental Health Services
Administration. (2016). Person- and family-centered
care and peer support. Retrieved October 23, 2017,
from www.samhsa.gov/section-223/care-coordination/
person-family-centered
84 Robinson, J. H., Callister, L. C., Berry, J. A., & Dearing,
K. A. (2008). Patient-centered care and adherence:
Defnitions and applications to improve outcomes.
Journal of the American Academy of Nurse Practitioners,
20(12), 600–607.
85 White, W., & Miller, W. (2007). The use of confrontation
in addiction treatment: History, science and time for
change. Counselor, 8(4), 12–30.
86 Lindgren, B. M., Eklund, M., Melin, Y., & Graneheim, U.
H. (2015). From resistance to existence—Experiences of
medication-assisted treatment as disclosed by people
with opioid dependence. Issues in Mental Health Nursing,
36(12), 963–970.
87 Stoller, K. B., Stephens, M. A. C., & Schorr, A. (2016).
Integrated service delivery models for opioid treatment
programs in an era of increasing opioid addiction,
health reform, and parity. Retrieved October 23, 2017,
from www.aatod.org/wp-content/uploads/2016/07
/2nd-Whitepaper-.pdf
88 Brooner, R. K., King, V. L., Kidorf, M., Schmidt, C. W., Jr.,
& Bigelow, G. E. (1997). Psychiatric and substance use
comorbidity among treatment-seeking opioid abusers.
Archives of General Psychiatry, 54(1), 71–80.
89 Savant, J. D., Barry, D. T., Cutter, C. J., Joy, M. T., Dinh,
A., Schottenfeld, R. S., & Fiellin, D. A. (2013). Prevalence
of mood and substance use disorders among patients
seeking primary care offce-based buprenorphine/
naloxone treatment. Drug and Alcohol Dependence,
127(1–3), 243–247.
90 Brooner, R. K., Kidorf, M. S., King, V. L., Peirce, J.,
Neufeld, K., Stoller, K., & Kolodner, K. (2013). Managing
psychiatric comorbidity within versus outside of
methadone treatment settings: A randomized and
controlled evaluation. Addiction, 108(11), 1942–1951.
91 Hser, Y. I., Evans, E., Grella, C., Ling, W., & Anglin, D.
(2015). Long-term course of opioid addiction. Harvard
Review of Psychiatry, 23(2), 76–89.
92 Flynn, P. M., Joe, G. W., Broome, K. M., Simpson, D. D.,
& Brown, B. S. (2003). Recovery from opioid addiction in
DATOS. Journal of Substance Abuse Treatment, 25(3),
177–186.
93 Havassy, B. E., Hall, S. M., & Wasserman, D. A. (1991).
Social support and relapse: Commonalities among
alcoholics, opiate users, and cigarette smokers. Addictive
Behaviors, 16(5), 235–246.
94 Tuten, M., & Jones, H. E. (2003). A partner’s drug-using
status impacts women’s drug treatment outcome. Drug
and Alcohol Dependence, 70(3), 327–330.
4-41
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
95 Schroeder, J. R., Latkin, C. A., Hoover, D. R., Curry, A. D.,
Knowlton, A. R., & Celentano, D. D. (2001). Illicit drug
use in one’s social network and in one’s neighborhood
predicts individual heroin and cocaine use. Annals of
Epidemiology, 11(6), 389–394.
96 Trocchio, S., Chassler, D., Storbjörk, J., Delucchi, K.,
Witbrodt, J., & Lundgren, L. (2013). The association
between self-reported mental health status and alcohol
and drug abstinence 5 years post-assessment for an
addiction disorder in U.S. and Swedish samples. Journal
of Addictive Diseases, 32(2), 180–193.
97 Kidorf, M., Latkin, C., & Brooner, R. K. (2016). Presence
of drug-free family and friends in the personal social
networks of people receiving treatment for opioid use
disorder. Journal of Substance Abuse Treatment, 70,
87–92.
98 Kidorf, M., Latkin, C., & Brooner, R. K. (2016). Presence
of drug-free family and friends in the personal social
networks of people receiving treatment for opioid use
disorder. Journal of Substance Abuse Treatment, 70,
87–92.
99 Substance Abuse and Mental Health Services
Administration. (2014). Improving cultural competence.
Treatment Improvement Protocol (TIP) Series 59. HHS
Publication No. (SMA) 14-4849. Rockville, MD: Substance
Abuse and Mental Health Services Administration.
100Substance Abuse and Mental Health Services
Administration. (2014). SAMHSA’s concept of trauma
and guidance for a trauma-informed approach. HHS
Publication No. (SMA) 14-4884. Rockville, MD: Substance
Abuse and Mental Health Services Administration.
101Kumar, N., Stowe, Z. N., Han, X., & Mancino, M. J. (2016).
Impact of early childhood trauma on retention and phase
advancement in an outpatient buprenorphine treatment
program. American Journal on Addictions, 25(7),
542–548.
102Barry, D. T., Beitel, M., Cutter, C. J., Garnet, B., Joshi, D.,
Rosenblum, A., & Schottenfeld, R. S. (2011). Exploring
relations among traumatic, posttraumatic, and physical
pain experiences in methadone-maintained patients.
Journal of Pain, 12(1), 22–28.
103Sansone, R. A., Whitecar, P., & Wiederman, M. W. (2009).
The prevalence of childhood trauma among those
seeking buprenorphine treatment. Journal of Addictive
Disorders, 28(1), 64–67.
104Lawson, K. M., Back, S. E., Hartwell, K. J., Moran-Santa,
M. M., & Brady, K. T. (2013). A comparison of trauma
profles among individuals with prescription opioid,
nicotine, or cocaine dependence. American Journal of
Addiction, 22(2), 127–131.
105Jessell, L., Mateu-Gelabert, P., Guarino, H., Vakharia, S. P.,
Syckes, C., Goodbody, E., … Friedman, S. (2017). Sexual
violence in the context of drug use among young adult
opioid users in New York City. Journal of Interpersonal
Violence, 32(19), 2885–2907.
106Amaro, H., Dai, J., Arévalo, S., Acevedo, A., Matsumoto,
A., Nieves, R., & Prado, G. (2007). Effects of integrated
trauma treatment on outcomes in a racially/ethnically
diverse sample of women in urban community-based
substance abuse treatment. Journal of Urban Health,
84(4), 508–522.
107Volkow, N. D., Koob, G. F., & McLellan, A. T. (2016).
Neurobiologic advances from the brain disease model
of addiction. New England Journal of Medicine, 374(4),
363–371.
108Edelman, E. J., Chantarat, T., Caffrey, S., Chaudhry, A.,
O’Connor, P. G., Weiss, L., ... Fiellin, L. E. (2014). The
impact of buprenorphine/naloxone treatment on HIV
risk behaviors among HIV-infected, opioid-dependent
patients. Drug and Alcohol Dependence, 139, 79–85.
109Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
110Rosenthal, R. N., Ling, W., Casadonte, P., Vocci, F.,
Bailey, G. L., Kampman, K., ... Beebe, K. L. (2013).
Buprenorphine implants for treatment of opioid
dependence: Randomized comparison to placebo and
sublingual buprenorphine/naloxone. Addiction, 108(12),
2141–2149.
111Sullivan, L. E., Moore, B. A., Chawarski, M. C., Pantalon,
M. V., Barry, D., O’Connor, P. G., ... Fiellin, D. A. (2008).
Buprenorphine/naloxone treatment in primary care is
associated with decreased human immunodefciency virus
risk behaviors. Journal of Substance Abuse Treatment,
35(1), 87–92.
112Substance Abuse and Mental Health Services
Administration. (2016). Buprenorphine. Retrieved
October 23, 2017, from www.samhsa.gov/medication
-assisted-treatment/treatment/buprenorphine
113Lovegrove, M. C., Mathew, J., Hampp, C., Governale,
L., Wysowski, D. K., & Budnitz, D. S. (2014). Emergency
hospitalizations for unsupervised prescription medication
ingestions by young children. Pediatrics, 134(4),
e1009–e1016.
114Hakkinen, M., Launiainen, T., Vuori, E., & Ojanpera, I.
(2012). Benzodiazepines and alcohol are associated with
cases of fatal buprenorphine poisoning. European Journal
of Clinical Pharmacology, 68(3), 301–309.
115Schuman-Olivier, Z., Hoeppner, B. B., Weiss, R. D.,
Borodovsky, J., Shaffer, H. J., & Albanese, M. J. (2013).
Benzodiazepine use during buprenorphine treatment for
opioid dependence: Clinical and safety outcomes. Drug
and Alcohol Dependence, 132(3), 580–586.
4-42
Medications for Opioid Use Disorder TIP 63
116Department of Health and Human Services. (2021,
April 28). Practice guidelines for the administration
of buprenorphine for treating opioid use disorder.
HHS Notice, 86 Fed. Reg. 22439. Retrieved
April 28, 2021, from www.federalregister.gov/
documents/2021/04/28/2021-08961/practice-guidelines-
for-the-administration-of-buprenorphine-for-treating-
opioid-use-disorder#:~:text=The%20Practice%20
Guidelines%20for%20the%20Administration%20of%20
Buprenorphine,training%2C%20counseling%20and%20
other%20ancillary%20services%20%28i.e%20
117Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R.,
Montejano, L. B., Dougherty, R. H., ... Delphin-Rittmon,
M. E. (2014). Medication-assisted treatment with
methadone: Assessing the evidence. Psychiatric Services,
65(2), 146–157.
118Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White,
J., & O’Brien, S. (2008). Exposure to opioid maintenance
treatment reduces long-term mortality. Addiction, 103(3),
462–468.
119Gowing, L. R., Farrell, M., Bornemann, R., Sullivan, L. E.,
& Ali, R. L. (2006). Brief report: Methadone treatment
of injecting opioid users for prevention of HIV infection.
Journal of General Internal Medicine, 21(2), 193–195.
120Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., ... O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
121Merlo, L. J., Greene, W. M., & Pomm, R. (2011).
Mandatory naltrexone treatment prevents relapse among
opiate-dependent anesthesiologists returning to practice.
Journal of Addiction Medicine, 5(4), 279–283.
122Washton, A. M., Gold, M. S., & Pottash, A. C. (1984).
Successful use of naltrexone in addicted physicians and
business executives. Advances in Alcohol and Substance
Abuse, 4(2), 89–96.
123Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(4), 1–45.
124Cornish, J. W., Metzger, D., Woody, G. E., Wilson, D.,
McLellan, A. T., Vandergrift, B., & O’Brien, C. (1997).
Naltrexone pharmacotherapy for opioid dependent
federal probationers. Journal of Substance Abuse
Treatment, 14(6), 529–534.
125Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2011(4), 1–45.
126Merlo, L. J., Greene, W. M., & Pomm, R. (2011).
Mandatory naltrexone treatment prevents relapse among
opiate-dependent anesthesiologists returning to practice.
Journal of Addiction Medicine, 5(4), 279–283.
127Substance Abuse and Mental Health Services
Administration. (2016). Medication-assisted treatment
of opioid use disorder pocket guide. HHS No. (SMA)
16-4892PG. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
128Faggiano, F., Vigna-Taglianti, F., Versino, E., & Lemma, P.
(2003). Methadone maintenance at different dosages for
opioid dependence. Cochrane Database of Systematic
Reviews, 2003(3), 1–45.
129Fareed, A., Casarella, J., Amar, R., Vayalapalli, S., &
Drexler, K. (2010). Methadone maintenance dosing
guideline for opioid dependence, a literature review.
Journal of Addictive Diseases, 29(1), 1–14.
130Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
131National Library of Medicine. (2015). VIVITROL –
naltrexone. Retrieved October 23, 2017, from
https://dailymed.nlm.nih.gov/dailymed/drugInfo
.cfm?setid=cd11c435-b0f0-4bb9-ae78-60f101f3703f
132Fiellin, D. A., Schottenfeld, R. S., Cutter, C. J., Moore, B.
A., Barry, D. T., & O’Connor, P. G. (2014). Primary care-
based buprenorphine taper vs maintenance therapy for
prescription opioid dependence: A randomized clinical
trial. JAMA Internal Medicine, 174(12), 1947–1954.
133Kakko, J., Svanborg, K. D., Kreek, M. J., & Heilig, M.
(2003, February 22). 1-year retention and social function
after buprenorphine-assisted relapse prevention
treatment for heroin dependence in Sweden: A
randomised, placebo-controlled trial. Lancet, 361(9358),
662–668.
134Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark,
H. W., Robillard, H., ... Hall, S. M. (2000). Methadone
maintenance vs 180-day psychosocially enriched
detoxifcation for treatment of opioid dependence: A
randomized controlled trial. JAMA, 283(10), 1303–1310.
135Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M.,
Connery, H. S., Dickinson, W., ... Ling, W. (2011).
Adjunctive counseling during brief and extended
buprenorphine-naloxone treatment for prescription
opioid dependence: A 2-phase randomized controlled
trial. Archives of General Psychiatry, 68(12), 1238–1246.
136Confdentiality of Substance Use Disorder Patient
Records; HHS Final Rule, 82 Fed. Reg. 6052 (January
18, 2017) (to be codifed at 42 CFR pt. 2). Retrieved
November 13, 2017, from www.federalregister.gov/
documents/2017/01/18/2017-00719/confdentiality
-of-substance-use-disorder-patient-records
4-43
TIP 63
Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and
Healthcare Professionals
137Jost, T. S. (2006). Appendix B: Constraints on sharing
mental health and substance-use treatment information
imposed by federal and state medical records privacy
laws. In Institute of Medicine (US) Committee on Crossing
the Quality Chasm: Adaptation to Mental Health and
Addictive Disorders, Improving the quality of healthcare
for mental and substance-use conditions. Quality Chasm
Series. Washington, DC: National Academies Press.
Retrieved January 3, 2018, from www.ncbi.nlm.nih.gov/
books/NBK19829
138Coviello, D. M., Zanis, D. A., Wesnoski, S. A., &
Alterman, A. I. (2006). The effectiveness of outreach
case management in re-enrolling discharged methadone
patients. Drug and Alcohol Dependence, 85(1), 56–65.
139Goldstein, M. F., Deren, S., Kang, S. Y., Des Jarlais, D. C.,
& Magura, S. (2002). Evaluation of an alternative program
for MMTP drop-outs: Impact on treatment re-entry. Drug
and Alcohol Dependence, 66(2), 181–187.
140Duncan, B. (2010). On becoming a better therapist.
Psychotherapy in Australia, 16(4), 42–51.
141Wampold, B. E. (2011). Qualities and actions of effective
therapists.
142American Medical Association. (2017). End the
epidemic. Retrieved October 23, 2017, from
https://end-overdose-epidemic.org/
143Kampman, K., & Jarvis, M. (2015). American Society of
Addiction Medicine (ASAM) national practice guideline
for the use of medications in the treatment of addiction
involving opioid use. Journal of Addiction Medicine, 9(5),
358–367.
144National Institute on Drug Abuse. (n.d.). Effective
treatments for opioid addiction. Retrieved October 23,
2017, from www.drugabuse.gov/publications
/effective-treatments-opioid-addiction/effective
-treatments-opioid-addiction
145Offce of the Surgeon General. (2016). Facing addiction in
America: The Surgeon General’s report on alcohol, drugs,
and health. Washington, DC: Department of Health and
Human Services.
146Carter, A., & Hall, W. (2007). The ethical use of
psychosocially assisted pharmacological treatments for
opioid dependence. Geneva, Switzerland: WHO Press.
147Equal Employment Opportunity Commission. (1992).
A technical assistance manual on the employment
provisions (Title I) of the Americans with Disabilities Act.
Washington, DC: Author.
148Friedmann, P. D., Hoskinson, R., Gordon, M., Schwartz,
R., Kinlock, T., Knight, K., ... Frisman, L. K. (2012).
Medication-assisted treatment in criminal justice agencies
affliated with the Criminal Justice-Drug Abuse Treatment
Studies (CJ-DATS): Availability, barriers & intentions.
Substance Abuse, 33(1), 9–18.
149Legal Action Center. (2011). Legality of denying access
to medication assisted treatment in the criminal justice
system. Retrieved October 23, 2017, from www.lac.org/
assets/fles/MAT_Report_FINAL_12-1-2011.pdf
150World Health Organization. (2009). Guidelines for the
psychosocially assisted pharmacological treatment of
opioid dependence. Geneva, Switzerland: WHO Press.
151Soyka, M., Träder, A., Klotsche, J., Haberthür, A.,
Bühringer, G., Rehm, J., & Wittchen, H. U. (2012).
Criminal behavior in opioid-dependent patients before
and during maintenance therapy: 6-year follow-up of
a nationally representative cohort sample. Journal of
Forensic Sciences, 57(6), 1524–1530.
152Substance Abuse and Mental Health Services
Administration. (2016). A collaborative approach to
the treatment of pregnant women with opioid use
disorders. HHS Publication No. (SMA) 16-4978. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
153Donovan, D. M., Ingalsbe, M. H., Benbow, J., & Daley,
D. C. (2013). 12-step interventions and mutual support
programs for substance use disorders: An overview.
Social Work in Public Health, 28(3–4), 313–332.
154Humphreys, K., Blodgett, J. C., & Wagner, T. H. (2014).
Estimating the effcacy of Alcoholics Anonymous without
self-selection bias: An instrumental variables re-analysis
of randomized clinical trials. Alcoholism: Clinical and
Experimental Research, 38(11), 2688–2694.
155McCrady, B. S., & Tonigan, S. (2014). Recent research into
twelve-step programs. In R. K. Ries, D. A. Fiellin, S. C.
Miller, & R. Saitz (Eds.), The ASAM principles of addiction
medicine (pp. 1043–1059). Philadelphia, PA: Wolters
Kluwer.
156Crape, B. L., Latkin, C. A., Laris, A. S., & Knowlton, A. R.
(2002). The effects of sponsorship in 12-step treatment
of injection drug users. Drug and Alcohol Dependence,
65(3), 291–301.
157Monico, L. B., Gryczynski, J., Mitchell, S. G., Schwartz, R.
P., O’Grady, K. E., & Jaffe, J. H. (2015). Buprenorphine
treatment and 12-step meeting attendance: Conficts,
compatibilities, and patient outcomes. Journal of
Substance Abuse Treatment, 57, 89–95.
158Gossop, M., Stewart, D., & Marsden, J. (2008).
Attendance at Narcotics Anonymous and Alcoholics
Anonymous meetings, frequency of attendance and
substance use outcomes after residential treatment for
drug dependence: A 5-year follow-up study. Addiction,
103(1), 119–125.
159Parran, T. V., Adelman, C. A., Merkin, B., Pagano, M.
E., Defranco, R., Ionescu, R. A., & Mace, A. G. (2010).
Long-term outcomes of offce-based buprenorphine/
naloxone maintenance therapy. Drug and Alcohol
Dependence, 106(1), 56–60.
4-44
Medications for Opioid Use Disorder TIP 63
160Narcotics Anonymous World Services. (2016). Narcotics
Anonymous and persons receiving medication-assisted
treatment. Chatsworth, CA: Author.
161Monico, L. B., Gryczynski, J., Mitchell, S. G., Schwartz, R.
P., O’Grady, K. E., & Jaffe, J. H. (2015). Buprenorphine
treatment and 12-step meeting attendance: Conficts,
compatibilities, and patient outcomes. Journal of
Substance Abuse Treatment, 57, 89–95.
162White, W., Galanter, M., Humphreys, K., & Kelly, J.
(2016). The paucity of attention to Narcotics Anonymous
in current public, professional, and policy responses to
rising opioid addiction. Alcoholism Treatment Quarterly,
34(4), 437–462.
163Kelly, J. F., Greene, M. C., & Bergman, B. G. (2014).
Do drug-dependent patients attending Alcoholics
Anonymous rather than Narcotics Anonymous do as well?
A prospective, lagged, matching analysis. Alcohol and
Alcoholism, 49(6), 645–653.
164Substance Abuse and Mental Health Services
Administration. (2015). Using technology-based
therapeutic tools in behavioral health services. Treatment
Improvement Protocol (TIP) Series 60. HHS Publication
No. (SMA) 15-4924. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
165White, W. L. (2011). Narcotics Anonymous and the
pharmacotherapeutic treatment of opioid addiction in
the United States. Chicago, IL: Great Lakes Addiction
Technology Transfer Center and Philadelphia Department
of Behavioral Health and Intellectual Disability Services.
166White, W., Galanter, M., Humphreys, K., & Kelly, J.
(2016). The paucity of attention to Narcotics Anonymous
in current public, professional, and policy responses to
rising opioid addiction. Alcoholism Treatment Quarterly,
34(4), 437–462.
167Ginter, W. (2012). Methadone Anonymous and mutual
support for medication-assisted recovery. Journal of
Groups in Addiction and Recovery, 7(2–4), 189–201.
168Ronel, N., Gueta, K., Abramsohn, Y., Caspi, N., &
Adelson, M. (2011). Can a 12-step program work in
methadone maintenance treatment? International Journal
of Offender Therapy and Comparative Criminology, 55(7),
1135–1153.
169Glickman, L., Galanter, M., Dermatis, H., Dingle, S.,
& Hall, L. (2004). Pathways to recovery: Adapting
12-step recovery to methadone treatment. Journal of
Maintenance in the Addictions, 2(4), 77–90.
170Palis, H., Marchand, K., Peng, D., Fikowski, J., Harrison,
S., Spittal, P., … Oviedo-Joekes, E. (2016). Factors
associated with perceived abuse in the health care system
among long-term opioid users: A cross-sectional study.
Substance Use and Misuse, 51(6), 763–776.
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
Substance Abuse and Mental Health
Services Administration
Part 5: Resources Related to Medications for Opioid Use Disorder
For Healthcare and Addiction Professionals, Policymakers, Patients, and Families
Part 5 of this Treatment Improvement Protocol (TIP) provides a collection of resources by
audience and a glossary of key terms to help readers better understand how Food and Drug
Administration (FDA)-approved medications can be used to treat opioid use disorder (OUD).
TIP Navigation
Executive Summary
For healthcare and addiction professionals,
policymakers, patients, and families
Part 1: Introduction to Medications for Opioid
Use Disorder Treatment
For healthcare and addiction professionals,
policymakers, patients, and families
Part 2: Addressing Opioid Use Disorder in
General Medical Settings
For healthcare professionals
Part 3: Medications for Opioid Use Disorder
For healthcare professionals
Part 4: Bringing Together Addiction Treatment
Counselors, Clients, and Healthcare
Professionals
For healthcare and addiction professionals
Part 5: Resources Related to Medications
for Opioid Use Disorder
For healthcare and addiction professionals,
policymakers, patients, and families
KEY MESSAGES
• Practice guidelines and decision-making
tools can help healthcare professionals
with OUD screening, assessment,
diagnosis, treatment planning, and
referral.
• Patient- and family-oriented resources
provide information about opioid
addiction in general; the role of
medication, behavioral and supportive
services, and mutual-help groups in the
treatment of OUD; how-tos for identifying
recovery support services; and how-
tos for locating medical and behavioral
health service providers who specialize
in treating OUD or other substance use
disorders (SUDs).
5-ii
TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 5 of 5
Contents
General Resources 5-1
Facts and Figures 5-1
Groups and Organizations 5-2
SAMHSA Publications 5-3
General Information 5-4
Practice Guidelines and Decision-Support Tools 5-8
Assessment Scales and Screening Tools 5-9
Resources for Counselors and Peer Providers 5-10
Organizations 5-10
Publications and Other Resources 5-11
Resources for Clients and Families 5-12
Organizations 5-12
Publications and Other Resources 5-13
Treatment Locators 5-14
Patient Success Stories 5-15
Online Boards and Chat Rooms 5-15
Provider Tools and Sample Forms 5-16
Provider Screening and Assessment Tools and Aids 5-16
TAPS Tool Part I 5-25
TAPS Tool Part 2 5-26
Provider Informational, Educational, and Decision-Making Tools 5-30
Sample Provider Forms 5-41
Pharmacy Tablet/Film Count Form 5-45
Glossary of TIP Terminology 5-56
Notes 5-59
5-1
MEDICATIONS FOR OPIOID USE DISORDERTIP 63
PART 5 of 5
Resources Related to Medications for
Opioid Use Disorder
There are numerous resources to help healthcare professionals and behavioral health service
providers better understand the use of FDA-approved medications for OUD. Many other
resources are available to help patients, their families and friends, and the general public better
understand OUD and the medications available to treat it and support recovery from it. Part 5
of this TIP provides an audience-segmented collection of resources and a glossary of key terms
related to OUD. It is of use to all interested readers.
General Resources
Facts and Figures
American Association for the Treatment of
Opioid Dependence (AATOD), Frequently
Asked Questions (www.aatod.org/resources
/frequently-asked-questions).
Centers for Disease Control and Prevention
(CDC), Smoking & Tobacco Use (www.cdc.gov
/tobacco/index.htm).
Legal Action Center (LAC), Medication-
Assisted Treatment for Opioid Addiction:
Myths and Facts (www.lac.org/assets/fles/Myth-
Fact-for-MAT.pdf).
Missouri Department of Mental Health,
Methadone Maintenance Myths and Resources
(https://dmh.mo.gov/media/pdf/methadone-
maintenance-myths-and-resources).
National Institute on Drug Abuse (NIDA)
(www.drugabuse.gov):
• Addiction Science (www.drugabuse.gov
/related-topics/addiction-science). Provides
two short videos that explain the nature
Opioid overdose caused
49,860 DEATHS
nationwide in 2019—
this exceeded the #
caused by motor vehicle
crashes.1,2
of addiction. These are useful in educating
people in primary care who suffer from
addiction. This site has links to publications
for professionals that explain the nature of
addiction.
• NIDAMED, Medical and Health Professionals
(www.drugabuse.gov/nidamed-medical
-health-professionals). Disseminates science-
based resources to healthcare professionals
on the causes and consequences of drug
use and addiction and advances in pain
management.
5-2
Medications for Opioid Use Disorder TIP 63
Offce of National Drug Control Policy,
Medication-Assisted Treatment for Opioid
Addiction (https://adai.uw.edu/pubs/infobriefs/
ondcpMATbrief.pdf): Offers a factsheet with a
useful summary of medication for OUD and its
effectiveness.
Partnership for Drug-Free Kids, Commentary:
Countering the Myths About Methadone
(www.drugfree.org/news-service/commentary
-countering-the-myths-about-methadone).
Substance Abuse and Mental Health Services
Administration (SAMHSA):
• Addiction Technology Transfer Center (ATTC)
(http://attcnetwork.org/home). Network
with 10 regional centers across the country
that provide training and information on
evidence-based practices to practitioners.
The ATTC website contains information
and resources about OUD medication for
clinicians, patients, and family members
(https://attcnetwork.org/centers/global-attc/
taking-action-address-opioid-misuse).
• State Opioid Treatment Authorities (SOTAs)
(https://dpt2.samhsa.gov/regulations/smalist
.aspx).
United States Surgeon General’s Report,
Facing Addiction in America: The Surgeon
General’s Report on Alcohol, Drugs, and
Health (https://addiction.surgeongeneral.gov).
Groups and Organizations
AATOD (www.aatod.org): Works with federal
and state agencies on opioid treatment policy
throughout the United States. Convenes con-
ferences every 18 months on evidence-based
clinical practice, current research, and organiza-
tional developments related to OUD treatment.
AATOD develops publications that serve as
resources for addiction counselors and peer
support providers.
American Academy of Addiction Psychiatry
(AAAP) (www.aaap.org): Offers education and
training materials on addiction psychiatry (e.g.,
webinars, continuing medical education courses).
American Society of Addiction Medicine
(ASAM) (www.asam.org): Provides medical
education and resources on the treatment of
SUDs, including OUD.
LAC (https://lac.org): Offers information about
the rights of people with criminal records,
HIV/AIDS, and SUDs.
National Alliance for Medication Assisted
Recovery (NAMA Recovery) (www.methadone
.org): Supports quality opioid agonist treatment
through its many U.S. chapters and its interna-
tional network of affliate chapters. Thousands of
methadone clients and healthcare professionals
belong to the organization.
National Alliance of Advocates for
Buprenorphine Treatment (www.naabt.org):
Aims to educate the public about opioid
addiction and buprenorphine as a treatment
option, to reduce prejudice and discrimination
against clients who have SUDs, and to connect
clients in need to qualifed treatment providers.
SAMHSA (www.samhsa.gov):
• Buprenorphine Practitioner Verifcation
for Pharmacists (www.samhsa.gov/bupe
/lookup-form)
• National Recovery Month (https://recovery
month.gov)
• Opioid Treatment Program (OTP) Directory
(https://dpt2.samhsa.gov/treatment)
• SOTAs (https://dpt2.samhsa.gov/regulations
/smalist.aspx)
5-3
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
SAMHSA Publications • Clinical Guidance for Treating Pregnant
All publications listed in this section are available
for free from SAMHSA’s publications ordering
webpage (https://store.samhsa.gov) or by calling
1-877-SAMHSA-7 (1-877-726-4727):
• TIP 42: Substance Use Disorder Treatment for
People With Co-Occurring Disorders
(https://store.samhsa.gov/product
/TIP-42-Substance-Abuse-Treatment-for
-Persons-With-Co-Occurring-Disorders
/SMA13-3992)
• TIP 54: Managing Chronic Pain in Adults With
or in Recovery From Substance Use Disorders
(https://store.samhsa.gov/product/TIP-54
-Managing-Chronic-Pain-in-Adults-With-or
-in-Recovery-From-Substance-Use-Disorders
/SMA13-4671)
• TIP 57: Trauma-Informed Care in Behavioral
Health Services (https://store.samhsa.gov
/product/TIP-57-Trauma-Informed-Care-in
-Behavioral-Health-Services/SMA14-4816)
• Advisory: An Introduction to Extended-
Release Injectable Naltrexone for the
Treatment of People With Opioid
Dependence (https://store.samhsa.gov
/product/An-Introduction-to-Extended
-Release-Injectable-Naltrexone-for-the
-Treatment-of-People-with-Opioid
-Dependence/SMA12-4682)
• Advisory: Sublingual and Transmucosal
Buprenorphine for Opioid Use
Disorder: Review and Update
(https://store.samhsa.gov/product/
Advisory-Sublingual-and-Transmucosal-
Buprenorphine-for-Opioid-Use-Disorder-/
SMA16-4938)
• Buprenorphine Quick Start Guide
(www.samhsa.gov/sites/default/fles/quick-
start-guide.pdf)
• Buprenorphine Quick Start Pocket Guide
(www.samhsa.gov/sites/default/fles/quick-
start-pocket.pdf)
and Parenting Women With Opioid Use
Disorder and Their Infants (https://store.
samhsa.gov/product/Clinical-Guidance-for-
Treating-Pregnant-and-Parenting-Women-
With-Opioid-Use-Disorder-and-Their-Infants/
SMA18-5054)
• Clinical Use of Extended-Release
Injectable Naltrexone in the Treatment
of Opioid Use Disorder: A Brief Guide
(https://store.samhsa.gov/product/
Clinical-Use-of-Extended-Release-
Injectable-Naltrexone-in-the-Treatment-
of-Opioid-Use-Disorder-A-Brief-Guide/
SMA14-4892R)
• A Collaborative Approach to the Treatment of
Pregnant Women With Opioid Use Disorders
(https://store.samhsa.gov/product/A
-Collaborative-Approach-to-the-Treatment
-of-Pregnant-Women-with-Opioid-Use
-Disorders/SMA16-4978)
• Decisions in Recovery: Treatment for Opioid
Use Disorders, Handbook (https://store
.samhsa.gov/product/SMA16-4993)
• Integrated Treatment for Co-Occurring
Disorders Evidence-Based Practices (EBP)
Kit (https://store.samhsa.gov/product/
Integrated-Treatment-for-Co-Occurring-
Disorders-Evidence-Based-Practices-EBP-KIT/
SMA08-4366)
• Technical Assistance Publication 32:
Clinical Drug Testing in Primary Care
(https://store.samhsa.gov/product/tap-
32-clinical-drug-testing-primary-care/
sma12-4668)
• What Are Peer Recovery Support Services?
(https://store.samhsa.gov/product/What-
Are-Peer-Recovery-Support-Services-/
sma09-4454)
5-4
Medications for Opioid Use Disorder TIP 63
General Information
Agency for Healthcare Research and Quality:
• Medication-Assisted Treatment Models of
Care for Opioid Use Disorder in Primary Care
Settings (www.ncbi.nlm.nih.gov/books
/NBK402352)
• Academy for Integrating Behavioral Health
and Primary Care (https://integrationacademy
.ahrq.gov)
American Academy of Family Physicians:
• Chronic Pain Management and Opioid
Misuse: A Public Health Concern (Position
Paper) (www.aafp.org/about/policies/all/pain
-management-opioid.html)
• Pain Management and Opioid Use Resources
(www.aafp.org/patient-care/public-health
/pain-opioids/resources.html)
ATTC Network (http://attcnetwork.org/home):
This nationwide network of SAMHSA-sponsored
regional centers is a multidisciplinary resource
for professionals in the addiction treatment and
recovery services felds. The network has many
valuable resources and projects of interest to
people involved in treating SUDs. Of particular
interest to readers of this TIP are the training
programs produced as part of the NIDA/
SAMHSA-ATTC Blending Initiative:
• Buprenorphine Treatment: Training for
Multidisciplinary Addiction Professionals
(https://attcnetwork.org/centers/global-attc/
product/buprenorphine-treatment-train-
ing-multidisciplinary-addiction)
• Buprenorphine Treatment for Young
Adults (https://attcnetwork.org/centers/
network-coordinating-offce/product/
buprenorphine-treatment-young-adults)
• Prescription Opioid Addiction Treatment
Study (POATS) (https://attcnetwork.org/
centers/network-coordinating-offce/
product/prescription-opioid-addiction-treat-
ment-study-poats)
BupPractice.com Federal Recordkeeping
Requirements for Buprenorphine Treatment
(https://docs.clinicaltools.com/pdf/Buppractice/
V5-Bup-How-To-Comply.pdf): Provides informa-
tion about federal recordkeeping requirements.
CDC Smoking & Tobacco Use (www.cdc.gov
/tobacco/index.htm): Includes resource links
for clinicians on smoking and the treatment of
tobacco use.
Centers for Medicare & Medicaid Services
(www.cms.gov/Medicare/Medicare-General
-Information/Telehealth/index.html): Gives
guidance on the delivery of telehealth.
Department of Health and Human Services
(HHS):
• Centers for Medicare & Medicaid
Services Clinical Laboratory Improvement
Amendments Application for Certifcation
(www.cms.gov/Medicare/CMS-Forms/CMS
-Forms/downloads/cms116.pdf)
• Medication Assisted Treatment for Opioid Use
Disorders: Final Rule (www.federalregister
.gov/documents/2016/07/08/2016-16120
/medication-assisted-treatment-for-opioid
-use-disorders)
Drug Enforcement Administration (DEA):
• DEA Requirements for DATA Waived
Physicians (www.deadiversion.usdoj.gov/pubs/
docs/index.html). Lists DEA requirements for
Drug Addiction Treatment Act of 2000 (DATA
2000)-waivered healthcare professionals.
• Form DEA-106, Report of Theft or Loss of
Controlled Substances (https://apps
.deadiversion.usdoj.gov/webforms/dtlLogin
.jsp). Provides instructions for completing
form DEA-106, which must be fled when
stored buprenorphine is lost or stolen.
Drugs.com:
• Buprenorphine Drug Interactions (www.drugs
.com/drug-interactions/buprenorphine-index
.html?flter=3&generic_only=)
• Drug Interactions Checker (www.drugs.com
/drug_interactions.php)
5-5
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
FDA:
• Approved Risk Evaluation and Mitigation
Strategy (REMS): Buprenorphine Transmucosal
Products for Opioid Dependence (www
.accessdata.fda.gov/scripts/cder/rems/index
.cfm?event=RemsDetails.page&REMS=9)
• REMS: Probuphine (buprenorphine hydro-
chloride) (www.accessdata.fda.gov/scripts
/cder/rems/index.cfm?event=IndvRemsDetails
.page&REMS=356)
• REMS: Sublocade (extended-release injectable
buprenorphine) (www.accessdata.fda.gov
/scripts/cder/rems/index.cfm?event
=IndvRemsDetails.page&REMS=376)
• REMS: Suboxone/Subutex (buprenorphine
and naloxone/buprenorphine) (www.accessdata
.fda.gov/scripts/cder/rems/index.cfm?event
=IndvRemsDetails.page&REMS=352)
• REMS: Vivitrol (extended-release naltrexone
[XR-NTX]) (www.vivitrolrems.com)
LAC (https://lac.org): LAC attorneys provide
legal advice by phone to service providers and
government agencies. They assist dozens of
agencies annually with questions about conf-
dentiality of treatment records, discrimination,
and other issues. LAC’s confdentiality hotline
provides information about the federal law
protecting the confdentiality of drug and alcohol
treatment and prevention records (42 CFR Part 2).
The hotline is free to New York treatment
providers and government agencies. Outside
New York, the hotline is accessible if the state
alcohol/drug oversight agency subscribes to
LAC’s Actionline service. To speak with a hotline
attorney, call LAC Monday through Friday 1−5
p.m. (Eastern Time Zone) at 1-212-243-1313, or
toll-free at 1-800-223-4044.
National Alliance of Advocates for
Buprenorphine Treatment 30−100 Patient
Limit (www.naabt.org/30_patient_limit.cfm):
Summarizes the DATA 2000 law.
National Association of State Controlled
Substances Authorities State Profles (www
.nascsa.org/stateprofles.htm): Contains a
directory of each state’s prescription drug
monitoring program (PDMP).
National Conference of State Legislatures
Drug Overdose Immunity and Good Samaritan
Laws (www.ncsl.org/research/civil-and-criminal
-justice/drug-overdose-immunity-good-samaritan
-laws.aspx): Provides information about naloxone
and Good Samaritan immunity.
National Institute on Alcohol Abuse and
Alcoholism (NIAAA) Professional Education
Materials (www.niaaa.nih.gov/publications
/clinical-guides-and-manuals): Provides
professional education materials; offers links
to screening, treatment planning, and general
information for clinicians in outpatient programs.
National Library of Medicine’s DailyMed:
• FDA label information for methadone (https://
dailymed.nlm.nih.gov/dailymed/search
.cfm?labeltype=all&query=METHADONE)
• FDA label information for XR-NTX (https://
dailymed.nlm.nih.gov/dailymed/drugInfo.cfm
?setid=cd11c435-b0f0-4bb9-ae78
-60f101f3703f)
NIDA:
• Available Treatments for Marijuana Use
Disorders (www.drugabuse.gov/publications
/research-reports/marijuana/available
-treatments-marijuana-use-disorders).
Provides information about treatment options
for individuals with marijuana use disorder.
• Naloxone for Opioid Overdose: Life-Saving
Science (www.drugabuse.gov/publications/
naloxone-opioid-overdose-life-saving-science).
Contains naloxone information for providers.
• NIDAMED, Clinical Resources (www.
drugabuse.gov/nidamed-medical-health-
professionals). Provides practice-related and
professional education-related resources.
5-6
Medications for Opioid Use Disorder TIP 63
• Medications To Treat Opioid Addiction (www
.drugabuse.gov/publications/research-reports
/medications-to-treat-opioid-addiction
/overview). Provides an overview of the need
for and effcacy of OUD medications and
discusses common misconceptions, impacts
on outcome, and use of OUD medications
with certain specifc populations.
• Effective Treatments for Opioid Addiction
(www.drugabuse.gov/publications
/effective-treatments-opioid-addiction
/effective-treatments-opioid-addiction).
• Therapeutic Communities (www.drugabuse
.gov/publications/research-reports
/therapeutic-communities/what-are
-therapeutic-communities). Gives a brief
overview of OUD medications and links to
additional information.
• Principles of Drug Addiction Treatment: A
Research-Based Guide (www.drugabuse.gov
/publications/principles-drug-addiction
-treatment-research-based-guide-third
-edition/preface). Discusses how OUD affects
the brain and covers the state of addiction
treatment in the United States, principles
of effective treatment, frequently asked
questions about OUD medication, evi-
dence-based approaches to treatment,
and additional resources.
• Principles of Adolescent Substance Use
Disorder Treatment: A Research-Based Guide
(www.drugabuse.gov/publications/principles
-adolescent-substance-use-disorder-treatment
-research-based-guide/introduction).
Discusses principles of SUDs in adolescents,
addresses frequently asked questions, summa-
rizes treatment settings and evidence-based
treatment approaches, and provides
treatment referral resources.
• Treating Opioid Use Disorder During
Pregnancy (www.drugabuse.gov/publications
/treating-opioid-use-disorder-during
-pregnancy/treating-opioid-use-disorder
-during-pregnancy). Addresses the risks of
OUD to the pregnant woman and the fetus,
briefy summarizes OUD pharmacotherapies
for use during pregnancy, and provides links
to additional information.
North American Syringe Exchange Program
(https://nasen.org/directory): Provides a national
directory of syringe exchange programs in the
United States.
Prescription Drug Abuse Policy System’s
Naloxone Overdose Prevention Laws
(http://pdaps.org/datasets/laws-regulating
-administration-of-naloxone-1501695139):
Provides a map with a link to each state’s
naloxone overdose prevention laws, including
policies on prescribing, dispensing, and civil
and criminal immunity.
Project Lazarus’s Naloxone: The Overdose
Antidote (www.projectlazarus.org/naloxone):
Provides guidance on administering naloxone.
Providers’ Clinical Support System’s
(PCSS’s) How To Prepare for a Visit From
the Drug Enforcement Agency Regarding
Buprenorphine Prescribing (http://pcssmat
.org/wp-content/uploads/2014/02/FINAL-How
-to-Prepare-for-a-DEA-Inspection.pdf): Provides
a description of the DEA inspection process and
how to comply with its requirements.
SAMHSA:
• Understanding the Final Rule for a Patient
Limit of 275 (www.samhsa.gov/medication-as-
sisted-treatment/training-materials-resources/
apply-for-practitioner-waiver). Provides infor-
mation about the fnal rule and how to use it
to increase patient access to medication for
OUD and associated reporting requirements.
5-7
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
• Buprenorphine Quick Start Guide (www.
samhsa.gov/sites/default/fles/quick-start-
guide.pdf). Provides a checklist to guide
healthcare professionals in prescribing
buprenorphine, managing withdrawal, and
providing maintenance therapy.
• Buprenorphine Quick Start Pocket Guide
(www.samhsa.gov/sites/default/fles/quick-
start-pocket.pdf): Provides a one-page fow
chart for induction onto buprenorphine.
• Buprenorphine Practice Guidelines (www.
federalregister.gov/documents/2021/04/
28/2021-08961/practice-guidelines-for-the-ad-
ministration-of-buprenorphine-for-treat-
ing-opioid-use-disorder). Provides information
about how providers may become exempt
from training and psychosocial service attesta-
tion requirements for obtaining a SAMHSA
X waiver.
• Buprenorphine Waiver Management (www.
samhsa.gov/medication-assisted-treatment/
training-materials-resources/apply-for-prac-
titioner-waiver). Provides information on the
buprenorphine waiver, including links to the
buprenorphine waiver application and an
explanation of the processes, requirements,
and recordkeeping strategies associated with
prescribing buprenorphine.
• Qualify for Nurse Practitioners (NPs) and
Physician Assistants (PAs) Waiver (www.
samhsa.gov/medication-assisted-treatment/
training-materials-resources/apply-for-
practitioner-waiver). Provides information for
NPs and PAs about the buprenorphine waiver
training, with links to trainings and the appli-
cation process.
• Buprenorphine Training for Physicians (www.
samhsa.gov/medication-assisted-treatment/
training-materials-resources/apply-for-prac-
titioner-waiver). Offers links to organizations
that provide buprenorphine training for
physicians.
• SAMHSA Opioid Overdose Prevention Toolkit
(https://store.samhsa.gov/product/Opioid-
Overdose-Prevention-Toolkit/SMA18-4742).
Prepares healthcare professionals, communi-
ties, and local governments with material to
develop practices and policies to help prevent
opioid-related overdoses and deaths. It
addresses issues for healthcare professionals,
frst responders, treatment providers, and
those recovering from opioid overdose.
• Federal Guidelines for Opioid Treatment
Programs (https://store.samhsa.gov/product
/Federal-Guidelines-for-Opioid-Treatment
-Programs/PEP15-FEDGUIDEOTP). Provides
updated guidelines for how OTPs can satisfy
the federal regulations.
• Form SMA-168 Opioid Treatment Exception
Request (www.samhsa.gov/medication
-assisted-treatment/opioid-treatment
-programs/submit-exception-request).
Provides instructions for physicians on how
to request exceptions to federal standards
for opioid treatment.
• Laws and Regulations (www.samhsa.gov
/about-us/who-we-are/laws-regulations).
Provides an overview and summary of the
most frequent questions about disclosure and
patient records pertaining to substance use
treatment that federal programs maintain.
• Substance Abuse in Brief Fact Sheet:
Introduction to Mutual-Support Groups
for Alcohol and Drug Abuse (http://www.
williamwhitepapers.com/pr/CSAT%20
Mutual%20Support%20Groups%202008.pdf).
Provides information to help medical and
behavioral health service providers understand
mutual-help groups and how to make referrals
to such groups.
5-8
Medications for Opioid Use Disorder TIP 63
• SAMHSA has developed several resources to
guide healthcare professionals in their use of
telehealth and telemedicine approaches for
OUD:
− In Brief: Rural Behavioral Health:
Telehealth Challenges and Opportunities
(https://store.samhsa.gov/product/
In-Brief-Rural-Behavioral-Health-
Telehealth-Challenges-and-Opportunities/
SMA16-4989)
− Certifed Community Behavioral Health
Clinics (CCBHCs) Using Telehealth or
Telemedicine (www.samhsa.gov/section
-223/care-coordination/telehealth
-telemedicine)
Practice Guidelines and Decision-
Support Tools
ASAM:
• Appropriate Use of Drug Testing in Clinical
Addiction Medicine (http://
download.lww.com /
wolterskluwer_vitalstream_com/PermaLink
/JAM/A/JAM_11_3_2017_06_02_SAFARIAN
_JAM-D-17-00020_SDC1.pdf). Details the
ASAM consensus statement on drug testing in
addiction treatment.
• The ASAM National Practice Guideline: For
the Use of Medication in the Treatment of
Addiction Involving Opioid Use (www.asam
.org/docs/default-source/practice-support
/guidelines-and-consensus-docs/asam
-national-practice-guideline-supplement
.pdf). Provides information on prescribing
methadone, buprenorphine, naltrexone,
and naloxone. The document also discusses
the needs of special populations, including
women during pregnancy, patients with
chronic pain, adolescents, individuals in the
criminal justice system, and patients with
co-occurring psychiatric conditions.
CDC:
• CDC Guideline for Prescribing Opioids for
Chronic Pain (www.cdc.gov/drugoverdose
/prescribing/guideline.html).
• Guideline Resources: Clinical Tools (www.cdc
.gov/drugoverdose/prescribing/clinical-tools
.html). Provides links and tools to help
clinicians prevent opioid overdose deaths.
Credible Meds (www.crediblemeds.org):
Maintains a list of medications that may increase
QTc intervals. Free registration is required to
access the most up-to-date list.
HHS:
• BeTobaccoFree.gov News and Resources
(https://betobaccofree.hhs.gov/quit-now
/index.html#professionals). Offers links for
clinicians that provide guidance on the care
for patients with nicotine addiction. The
Resources section is at the bottom of the
page linked here.
• BeTobaccoFree.gov Nicotine Addiction and
Your Health (https://betobaccofree.hhs.gov/).
Provides information on nicotine addiction
and its health effects.
Institute for Research, Evaluation, and
Training in Addictions’ Management of
Benzodiazepines in Medication-Assisted
Treatment (https://ireta.org/wp-content/
uploads/2018/03/BP_Guidelines_for_
Benzodiazepines.pdf): Provides information on
managing benzodiazepine use in patients taking
medications for OUD.
PCSS for Medication Assisted Treatment
(https://pcssnow.org/): Provides buprenorphine
waiver training for clinicians (physicians, NPs,
and PAs).
PCSS Mentoring Program (https://pcssnow.
org/mentoring/): Gives providers guidance on
prescribing OUD medications. This national
network of experienced providers is available at
no cost. Mentors provide support by telephone,
email, or in person if possible.
5-9
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
PCSS Models of Buprenorphine Induction
(http://pcssmat.org/wp-content/uploads/
2015/02/Buprenorphine-Induction-Online-
Module.pdf): Provides information about various
buprenorphine induction approaches including
in-offce, non-OTP, and at-home dosing.
Prescribe To Prevent (http://prescribeto
prevent.org): Provides information about naloxone
prescribing for overdose prevention, including
educational patient handouts and videos.
SAMHSA:
• Buprenorphine (www.samhsa.gov/medication
-assisted-treatment/treatment/buprenorphine).
• Naltrexone (www.samhsa.gov/medication
-assisted-treatment/treatment/naltrexone).
• Decisions in Recovery: Treatment for Opioid
Use Disorder, Planning for Success (https://
store.samhsa.gov/product/Decisions-
in-Recovery-Treatment-for-Opioid-Use-
Disorders/SMA16-4993). Provides assistance
in developing a recovery plan.
• Bringing Recovery Supports to Scale Technical
Assistance Center Strategy (www.samhsa.gov
/brss-tacs) and Shared Decision-Making Tools
(www.samhsa.gov/brss-tacs/recovery-support
-tools/shared-decision-making). Offers training
and technical assistance on many topics related
to medication for OUD, including recovery-
oriented systems of care, mutual-support
groups, capacity building, leadership by people
in recovery and family members, certifcation
requirements for peer specialists and mutual-
support group coaches, and core competencies
for recovery-oriented behavioral health workers.
• Pharmacologic Guidelines for Treating
Individuals With Post-Traumatic Stress
Disorder and Co-Occurring Opioid Use
Disorders (https://store.samhsa.gov/
product/pharmacologic-guidelines-
treating-individuals-post-traumatic-stress-
disorder-co-occurring).
Veterans Administration (VA)/Department of
Defense (DoD) Clinical Practice Guideline for
the Management of Substance Use Disorders
(www.healthquality.va.gov/guidelines/MH/
sud/VADoDSUDCPGRevised22216.pdf):
Provides information on screening, assessment,
and treatment of OUD as well as other SUDs. It
is primarily for VA and DoD healthcare providers
and others involved in the care of service
members or veterans with an SUD.
Assessment Scales and Screening Tools
AAAP, Education & Training (www.aaap.org/
education/educational-opportunities/): Provides
Performance-in-Practice Clinical Modules for
alcohol use disorder and tobacco use disorder.
American Psychiatric Nurses Association,
Tobacco & Nicotine Use Screening Tools &
Assessments (www.apna.org/i4a/pages/index
.cfm?pageID=6150): Provides the Fagerström
screening tools for nicotine dependence and
smokeless tobacco and a screening checklist
for adolescent tobacco use.
ASAM Appropriate Use of Drug Testing in
Clinical Addiction Medicine (www.asam.org/
Quality-Science/quality/drug-testing): Gives in-
formation on the appropriate use of drug testing
in identifying, diagnosing, and treating people
with or at risk for SUDs.
Clinical Institute Narcotic Assessment Scale
for Withdrawal Symptoms (www.ncpoep.org
/wp-content/uploads/2015/02/Appendix_7
_Clinical_Institute_Narcotic_Assessment_CINA
_Scale_for_Withdrawal_Symptoms.pdf).
• General Principles for the Use of
Pharmacological Agents To Treat Individuals
With Co-Occurring Mental and Substance
Use Disorders (https://store.samhsa.gov/
sites/default/files/d7/priv/sma12-4689.pdf).
5-10
Medications for Opioid Use Disorder TIP 63
NIDA, Screening Tools and Prevention (www.
drugabuse.gov/nidamed-medical-health-
professionals/screening-tools-prevention): Gives
resources such as an evidence-based screening
tool chart for adolescents and adults and drug
use screening tool supports; also has a clinician
resource and quick reference guide for drug
screening in general medical settings.
U.S. Preventive Services Task Force
Final Recommendation Statement—
Unhealthy Drug Use: Screening (https://
uspreventiveservicestaskforce.org/uspstf/
recommendation/drug-use-illicit-screening):
Includes recommendations about the screening
of adults in primary care for illicit drug use and
prescription medication misuse.
World Health Organization Guidelines for
the Psychosocially Assisted Pharmacological
Treatment of Opioid Dependence (www.ncbi
.nlm.nih.gov/books/NBK143183): Includes
links to the Clinical Opiate Withdrawal Scale
(www.drugabuse.gov/sites/default/fles/fles
/ClinicalOpiateWithdrawalScale.pdf) and other
opioid withdrawal scales from Annex 10 of the
guidelines.
Resources for Counselors and
Peer Providers
Organizations
Community Care Behavioral Health
Organization (www.ccbh.com): A provider
network focused on recovery that has published
Supporting Recovery From Opioid Addiction:
Community Care Best Practice Guidelines for
Recovery-Oriented Methadone Maintenance
(www.williamwhitepapers.com/pr/Recovery-
oriented%20Methadone%20Maintenance%20
Best%20Practice%20Guidelines%202014%20
-%20CCBHO.pdf), a set of recovery-orient-
ed practice implementation guidelines for
methadone programs.
Faces & Voices of Recovery (https://facesand
voicesofrecovery.org): Dedicated to organizing
and mobilizing the millions of Americans in
recovery from addiction to alcohol and drugs,
their families and friends, and other allies into
recovery community organizations and networks.
Faces & Voices of Recovery promotes the
right resources to recover through advocacy,
education, and demonstration of the power and
proof of long-term recovery.
Medication-Assisted Recovery Services
(MARS) Project (www.marsproject.org): A
peer-initiated, peer-based recovery support
project sponsored by NAMA Recovery that
offers, among other resources, an educational
video about the MARS peer support program
and an online network for MARS peer support
personnel:
• MARS Project Video (www.marsproject.org).
• New York State Peer Recovery Network, Peers
Organizing for Results Through Advocacy
and Leadership (PORTAL) (http://marsproject.
org/). Created to help peers in recovery
more effectively organize their communities,
communicate with each other, and create a
stronger voice for advocacy efforts.
National Association of Peer Supporters (www.
inaops.org/): An organization for mental health
and addiction peer recovery support specialists,
recovery coaches, recovery educators and
trainers, administrators of consumer-operated or
peer-run organizations, and others.
Pillars of Peer Support Services (www.pillarsof
peersupport.org): Develops and fosters the use
of Medicaid funding to support peer recovery
services in state mental health systems of care.
Recovery Community Services Program—
Statewide Network (www.samhsa.gov/grants
/grant-announcements/ti-14-001): A SAMHSA
grant program for peer-to-peer recovery support
services that help people initiate and sustain
recovery from SUDs.
5-11
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Publications and Other Resources
ATTC’s Recovery-Oriented Methadone
Maintenance (http://www.williamwhitepa-
pers.com/pr/2011%20Bamber-White%20
Dialogue%20on%20Recovery-Oriented%20
Methadone%20Maintenace.pdf): This guide
is the most thorough document on this topic
currently available and is applicable to clients
receiving other medications for OUD.
Community Care Behavioral Health
Organization: These publications outline phase-
specifc tasks and accompanying strategies for
programs that serve clients who take methadone
or buprenorphine:
• Supporting Recovery From Opioid Addiction:
Community Care Best Practice Guidelines for
Recovery-Oriented Methadone Maintenance
(www.williamwhitepapers.com/pr/Recovery
-oriented%20Methadone%20Maintenance
%20Best%20Practice%20Guidelines%20
2014%20-%20CCBHO.pdf).
• Supporting Recovery From Opioid Addiction:
Community Care Best Practice Guidelines for
Buprenorphine and Suboxone (http://www.
williamwhitepapers.com/pr/Community%20
Care%20Best%20Practice%20Guidelines%20
for%20Buprenorphine%20and%20
Suboxone%202014.pdf).
Narcotics Anonymous (NA) (www.na.org): The
organization’s most recent statement on medi-
cations for treating OUD—Narcotics Anonymous
and Persons Receiving Medication-Assisted
Treatment—is available online (www.na.org
/admin/include/spaw2/uploads/pdf/pr/2306
_NA_PRMAT_1021.pdf).
SAMHSA (https://store.samhsa.gov): This
agency oversees medications to treat opioid
addiction, including methadone, buprenorphine,
and naltrexone; sets regulations; guides policy;
and offers information and resources for the
feld. SAMHSA has many recovery-oriented
publications for providers:
• Medication-Assisted Recovery: Medication
Assisted Peer Recovery Support Services
Meeting Report (www.samhsa.gov/sites
/default/fles/programs_campaigns
/medication_assisted/dear_colleague
_letters/2015-prss-summary-report.pdf).
• Financing Recovery Support Services: Review
and Analysis of Funding Recovery Support
Services and Policy Recommendations
(https://facesandvoicesofrecovery.org/wp-
content/uploads/2019/06/Financing-
Recovery-Support-Services.pdf).
• SAMHSA’s Working Defnition of Recovery
(https://store.samhsa.gov/product/
SAMHSA-s-Working-Defnition-of-Recovery/
PEP12-RECDEF).
• Access to Recovery Approaches to Recovery-
Oriented Systems of Care (http://www.william-
whitepapers.com/pr/ATR%20Approaches%20
to%20ROSC%202009.pdf).
• Building Bridges—Co-Occurring Mental
Illness and Addiction: Consumers and Service
Providers, Policymakers, and Researchers in
Dialogue (https://permanent.access.gpo.gov/
lps80206/SMA04-3892.pdf).
Selected Papers of William L. White (www
.williamwhitepapers.com): Contains papers,
monographs, and presentations on recovery,
including recovery-oriented methadone main-
tenance, methadone and anti-medication bias,
discrimination and methadone, NA and the
pharmacotherapeutic treatment of OUD, and
co-participation in 12-Step mutual-support
groups and methadone maintenance.
5-12
Medications for Opioid Use Disorder TIP 63
Resources for Clients and Families
Organizations
AATOD (www.aatod.org): Offers a variety of
resources, news releases about medication for
the treatment of OUD, and information about its
national conferences.
Al-Anon Family Groups (www.al-anon.org):
Describes group meetings where friends and
family members of people with substance use
issues share their experiences and learn how
to apply the principles of the Al-Anon program
to their individual situations. Sponsorship gives
members the chance to get personal support
from more experienced individuals in the
program.
Alcoholics Anonymous (AA) (www.aa.org):
Offers group meetings for people who have
problems relating to drinking and wish to stop.
AA sponsors provide members with more
personal support from experienced individuals.
Many people who are taking medication to treat
OUD fnd AA increasingly receptive to their
decisions about medication, and AA meetings
are more widely available to these individuals.
ASAM: Provides patient and family education
tools about addiction in general and OUD
specifcally:
• Patient Resources (www.asam.org/resources
/patientresources)
• Opioid Addiction Treatment: A Guide
for Patients, Families, and Friends
(http://eguideline.guidelinecentral.com
/i/706017-asam-opioid-patient-piece/0?)
Double Trouble in Recovery (http://www.bhevo-
lution.org/public/doubletroubleinrecovery.page):
Describes a fellowship of people who support
each other in recovering from substance use and
mental disorders.
Dual Recovery Anonymous (www.draonline.org):
Presents information on mutual-help organiza-
tion that follows 12-Step principles in supporting
people recovering from addiction and emotional
or mental illness. Focuses on preventing relapse
and actively improving members’ quality of life
through a community of mutual support.
Faces & Voices of Recovery (https://facesand
voicesofrecovery.org): Offers recovery stories,
news, events information, publications, and
webinars.
Heroin Anonymous (https://heroinanonymous.
org/): Describes a nonproft fellowship of
individuals in recovery from heroin addiction
committed to helping each other stay sober.
This organization holds local support meetings, a
directory of which can be found on its website.
LAC (https://lac.org): Offers information about
the rights of people with criminal records,
HIV/AIDS, and SUDs.
Learn to Cope (www.learn2cope.org):
Describes a secular mutual-help group that offers
education, resources, and peer support for the
families of people with SUDs (although the focus
is primarily on OUD). The organization maintains
an online forum, but groups are only available in
a few states.
NA (www.na.org): Provides a global, community-
based organization with a multilingual, multi-
cultural membership that supports addiction
recovery via a 12-Step program, including
regular group meeting attendance. Members
hold nearly 67,000 meetings weekly in 139
countries. NA is an ongoing support network
for maintaining a drug-free lifestyle. NA doesn’t
focus on a particular addictive substance.
NAMA Recovery (www.methadone.org): Offers
an education series, provides training and
certifcation for Certifed MAT Advocates, and
has local chapters and international affliates that
act to advocate for methadone patients. It has
a helpful webpage titled FAQs About Advocate
Training and Certifcation (www.methadone.org
/certifcation/faq.html).
5-13
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Nar-Anon Family Groups (www.nar-anon.org):
Provides group meetings where friends and
family of people with drug use problems can
share their experiences and learn to apply
the 12-Step Nar-Anon program to their lives.
Nar-Anon groups also offer more individualized
support from experienced individuals in the
program who act as sponsors.
National Alliance on Mental Illness (NAMI)
(www.nami.org): Describes the largest grassroots
educational, peer support, and mental health
advocacy organization in the United States.
Founded in 1979 by a group of family members
of people with mental disorders, NAMI has
developed into an association of hundreds
of local affliates, state organizations, and
volunteers.
Parents of Addicted Loved Ones (https://
palgroup.org): Presents a secular support group
for parents who have a child with an SUD. The
organization has meetings in only some states
but also hosts telephone meetings.
Pills Anonymous (www.pillsanonymous.org):
Offers a 12-Step mutual-support group that
holds regular meetings in which individuals in
recovery from addiction to pills share their expe-
riences, build their strengths, and offer hope for
recovery to one another.
Self-Management for Addiction Recovery
(SMART Recovery) (www.smartrecovery.org):
Is a self-empowering addiction recovery support
group; participants learn science-based tools
for addiction recovery and have access to an
international recovery community of mutual-help
groups.
Stop Stigma Now (www.stopstigmanow.org):
Describes an advocacy organization that works
to eradicate prejudice associated with taking
medication to treat OUD and offers resources
and a media library.
Women for Sobriety (https://womenfor-
sobriety.org/): Offers an abstinence-based
mutual-help group that helps women fnd their
individual paths to recovery by acknowledging
the unique needs women have in recovery.
This organization is not affliated with any other
recovery organization. It offers recovery tools to
help women in recovery develop coping skills
focused on emotional growth, spiritual growth,
self-esteem, and a healthy lifestyle.
Publications and Other Resources
AAAP Patient Resources (www.aaap.org
/patient-resources/helpful-links): Offers resources
and publications for patients and their families.
Addiction Treatment Forum, Narcotics
Anonymous and the Pharmacotherapeutic
Treatment of Opioid Addiction in the United
States (http://atforum.com/documents
/2011NAandMedication-assistedTreatment.pdf):
Presents William White’s publication for people
receiving medication for OUD that gives infor-
mation on the pros and cons of 12-Step groups
and how to prepare for meetings.
ASAM, Opioid Addiction Treatment: A Guide
for Patients, Families, and Friends (http://
eguideline.guidelinecentral.com/i/706017-asam
-opioid-patient-piece): Provides a guide about
the treatment of OUD for patients, families, and
friends.
HHS:
• Smokefree.gov (https://smokefree.gov).
Provides useful information that helps indi-
viduals in planning and maintaining tobacco
cessation.
• BeTobaccoFree.gov (https://betobaccofree.
hhs.gov/): Provides information for individuals
struggling with nicotine addiction and links for
clinicians that provide guidance on the care
for patients with nicotine addiction.
LAC (https://lac.org/resources/substance-use
-resources/medication-assisted-treatment
-resources). Maintains a library of documents
related to medication for the treatment of OUD
and other resources, including an advocacy
toolkit, sample support letter form, training
materials, and webinars:
5-14
Medications for Opioid Use Disorder TIP 63
• Driving on Methadone or Buprenorphine
(Suboxone): DUI? (www.lac.org/assets/fles/
Driving-on-Methadone-or-Suboxone-DUI.pdf)
factsheet.
• Medication-Assisted Treatment for Opioid
Addiction: Myths and Facts (www.lac.org/
assets/fles/Myth-Fact-for-MAT.pdf) factsheet.
NAMA Recovery (www.methadone.org): Offers
many resources and training opportunities to
become a certifed advocate for medication for
OUD and provides links to resources related to
medication for the treatment of OUD.
National Council on Alcoholism and Drug
Dependence’s Consumer Guide to Medication-
Assisted Recovery (www.williamwhitepapers.
com/pr/NCADD%20Consumer%20Guide%20
to%20Medication-assisted%20Recovery%20
2011.pdf).
NIAAA’s Rethinking Drinking (www.rethinking
drinking.niaaa.nih.gov/help-links): Provides links
to patient and family education, help lines, and
other recovery resources.
SAMHSA (https://store.samhsa.gov): Provides
patient and family educational tools about
OUD and medication treatment for OUD.
The resources below are available in several
languages, including Spanish and Russian:
• Decisions in Recovery: Treatment for Opioid
Use Disorders (https://store.samhsa.gov
/product/Decisions-in-Recovery-Treatment
-for-Opioid-Use-Disorders/SMA16-4993).
Helps clients identify an appropriate path of
recovery from OUD.
• The Facts About Buprenorphine
for Treatment of Opioid Addiction
(https://store.samhsa.gov/product/
The-Facts-about-Buprenorphine-
for-Treatment-of-Opioid-Addiction/
SMA15-4442).
• The Facts About Naltrexone for Treatment of
Opioid Addiction (https://permanent.access.
gpo.gov/gpo20171/naltrexone-facts.pdf).
Treatment Locators
Faces & Voices of Recovery Guide to Mutual
Aid Resources (http://facesandvoicesof
recovery.org/resources/mutual-aid-resources):
Offers a comprehensive list of 12-Step and non-
12-Step recovery support groups throughout the
United States and online.
National Alliance of Advocates for
Buprenorphine Treatment (www.treatment
match.org/TM_index.php): Offers a free, 24/7
anonymous treatment-matching service for
patients and providers.
Probuphine Healthcare Provider Locator
(https://probuphinerems.com/fnd-probu-
phine/): Offers a list of healthcare professionals
who prescribe, insert, and/or remove buprenor-
phine implants.
• Know Your Rights: Rights for Individuals on
Medication-Assisted Treatment (www.samhsa.
gov/sites/default/files/programs_campaigns/
medication_assisted/Know-Your-Rights-
Brochure.pdf).
• Medication-Assisted Treatment for Opioid
Addiction: Facts for Families and Friends
(https://portal.ct.gov/-/media/DMHAS/
Opioid-Resources/MATInfoFamilyFriendspdf.
pdf).
• What Every Individual Needs To Know
About Methadone Maintenance Treatment
(https://roar.nevadaprc.org/system/
documents/3100/original/NPRC.168.
WhatEveryIndividualNeedsToKnow.
pdf?1435165554).
• What Is Substance Abuse Treatment?
A Booklet for Families (https://store.
samhsa.gov/product/What-Is-Substance-
Abuse-Treatment-A-Booklet-for-Families/
SMA14-4126).
5-15
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
SAMHSA:
• Behavioral Health Treatment Services Locator
is a directory of inpatient treatment providers
(https://fndtreatment.samhsa.gov).
• Behavioral Health Treatment Services Locator:
Self-Help, Peer Support, and Consumer
Groups (Addiction) provides a directory for
consumers (https://fndtreatment.samhsa.
gov/).
• Buprenorphine Treatment Practitioner Locator
provides an interactive treatment locator of
providers who prescribe buprenorphine (www
.samhsa.gov/medication-assisted-treatment
/physician-program-data/treatment-physician
-locator).
• Opioid Treatment Program Directory provides
an interactive SAMHSA OTP treatment locator
(https://dpt2.samhsa.gov/treatment/directory
.aspx).
VA Substance Use Disorder Program Locator
(www.va.gov/directory/guide/SUD.asp): Provides
an interactive treatment locator for VA SUD
treatment programs.
Patient Success Stories
Patients’ success stories highlight the powerful
ways in which medication for the treatment of
OUD can help people achieve remission and
recovery. Examples of patient success stories
include the following:
• Carol (https://vimeo.com/105287902)
• Brandon (https://vimeo.com/105078010)
• Archie (www.youtube/iHJ6K4VQvrw?list
=PLGV_2NAg58zkUOZRupfKc6_Z7jaBf7h-V)
• MARS Project Video (www.marsproject.org)
Online Boards and Chat Rooms
12-Step Forums: A variety of NA and AA
meetings are available online, each with its own
perspective on medication:
• The AA online intergroup directory lists
numerous online AA meetings, which occur
at specifc times (https://aa-intergroup.org/).
• The NA chatroom asks that participants not
talk about medication (www.nachatroom.net).
Online Forums and Groups: Many medication-
assisted recovery organizations maintain an
online presence for creating online mutual-
support and chat opportunities:
• Heroin Anonymous (https://heroinanonymous.
org/).
• NAMA Recovery (http://www.methadone.
org/).
• Stop Stigma Now (http://www.stopstigmanow.
org/).
SMART Recovery Online Forum (www.smart
recovery.org/community/forum.php): An online
group that welcomes new members.
We Speak Methadone (and Buprenorphine)
(www.methadone.org/wespeakmethadone):
A discussion forum for medication-assisted
treatment patients, their families, and advocates.
5-16
Medications for Opioid Use Disorder TIP 63
Provider Tools and Sample Forms
Provider Screening and Assessment Tools and Aids
Alcohol Use Disorders Identifcation Test (AUDIT)
1. How often do you have a drink containing
alcohol?
(0) Never [Skip to Questions 9–10]
(1) Monthly or less
(2) 2 to 4 times a month
(3) 2 to 3 times a week
(4) 4 or more times a week
6. How often during the last year have you
needed an alcoholic drink frst thing in the
morning to get yourself going after a night of
heavy drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
2. How many drinks containing alcohol do you
have on a typical day when you are drinking?
(0) 1 or 2
(1) 3 or 4
(2) 5 or 6
(3) 7, 8, or 9
(4) 10 or more
7. How often during the last year have you had a
feeling of guilt or remorse after drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
3. How often do you have six or more drinks on
one occasion?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
Skip to Questions 9 and 10 if total score for
Questions 2 and 3 = 0
8. How often during the last year have you been
unable to remember what happened the night
before because you had been drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
4. How often during the last year have you found
that you were not able to stop drinking once
you had started?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
9. Have you or someone else been injured as a
result of your drinking?
(0) No
(2) Yes, but not in the last year
(4) Yes, during the last year
5. How often during the last year have you failed
to do what was normally expected from you
because of drinking?
(0) Never
(1) Less than monthly
(2) Monthly
(3) Weekly
(4) Daily or almost daily
10. Has a relative, friend, doctor, or another health
professional expressed concern about your
drinking or suggested you cut down?
(0) No
(2) Yes, but not in the last year
(4) Yes, during the last year
Note: Add up the points associated with answers. A score of 8 or more is considered a positive test for unhealthy drinking.
Adapted from material in the public domain.3 Available online (http://auditscreen.org).
5-17
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Stable Resource Toolkit
Audit-C – Overview
The AUDIT-C is a 3-item alcohol screen that can help identify persons who are hazardous drinkers or have active
alcohol use disorders (including alcohol abuse or dependence). The AUDIT-C is a modifed version of the 10 question
AUDIT instrument.
Clinical Utility
The AUDIT-C is a brief alcohol screen that reliably identifes patients who are hazardous drinkers or have active
alcohol use disorders.
Scoring
The AUDIT-C is scored on a scale of 0-12.
Each AUDIT-C question has 5 answer choices. Points allotted are:
a = 0 points, b = 1 point, c = 2 points, d = 3 points, e = 4 points
• In men, a score of 4 or more is considered positive, optimal for identifying hazardous drinking or active alcohol use
disorders.
• In women, a score of 3 or more is considered positive (same as above).
• However, when the points are all from Question #1 alone (#2 & #3 are zero), it can be assumed that the patient is
drinking below recommended limits and it is suggested that the provider review the patient’s alcohol intake over
the past few months to confrm accuracy.
• Generally, the higher the score, the more likely it is that the patient’s drinking is affecting his or her safety.
Psychometric Properties
For identifying patients with heavy/hazardous drinking and/or Active-DSM alcohol abuse or dependence
MEN1 WOMEN2
≥3 Sens: 0.95 / Spec. 0.60 Sens: 0.66 / Spec. 0.94
≥4 Sens: 0.86 / Spec. 0.72 Sens: 0.48 / Spec. 0.99
For identifying patients with active alcohol abuse or dependence
MEN1 WOMEN2
≥3 Sens: 0.90 / Spec. 0.45 Sens: 0.80 / Spec. 0.87
≥4 Sens: 0.79 / Spec. 0.56 Sens: 0.67 / Spec. 0.94
1. Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT Alcohol Consumption Questions (AUDIT-C): An effective brief screening test
for problem drinking. Arch Internal Med. 1998 (3): 1789-1795.
2. Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorders Identifcation Test (AUDIT):
Validation in a female veterans affairs patient population. Arch Internal Med Vol 165, April 2003: 821-829.
Continued on next page
5-18
Medications for Opioid Use Disorder TIP 63
AUDIT-C Questionnaire
Patient Name: _____________________________________________________ Dates of Visit: ______________________
1. How often do you have a drink containing alcohol?
□ a. Never
□ b. Monthly or less
□ c. 2-4 times a month
□ d. 2-3 times a week
□ e. 4 or more times a week
2. How many standard drinks containing alcohol do you have on a typical day?
□ a. 1 or 2
□ b. 3 or 4
□ c. 5 or 6
□ d. 7 to 9
□ e. 10 or more
3. How often do you have six or more drinks on one occasion?
□ a. Never
□ b. Less than monthly
□ c. Monthly
□ d. Weekly
□ e. Daily or almost daily
AUDIT-C is available for use in the public domain.
Reprinted from material in the public domain.4
5-19
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Drug Abuse Screening Test (DAST-10)
General Instructions
“Drug use” refers to (1) the use of prescribed or over-the-counter drugs in excess of the directions, and (2) any nonmedical
use of drugs. The various classes of drugs may include cannabis (i.e., marijuana, hashish), solvents (e.g., paint thinner), tran-
quilizers (e.g., Valium), barbiturates, cocaine, stimulants (e.g., speed), hallucinogens (e.g., LSD), or narcotics (e.g., heroin).
The questions do not include alcoholic beverages.
Please answer every question. If you have trouble with a question, then choose the response that is mostly right.
Segment: ____________ Visit Number: ___________ Date of Assessment: ______/_______/________
These questions refer to drug use in the past 12 months. Please answer No or Yes.
1. Have you used drugs other than those required for medical reasons? □ No □ Yes
2. Do you use more than one drug at a time? □ No □ Yes
3. Are you always able to stop using drugs when you want to? □ No □ Yes
4. Have you had “blackouts” or “fashbacks” as a result of drug use? □ No □ Yes
5. Do you ever feel bad or guilty about your drug use? □ No □ Yes
6. Does your spouse (or parents) ever complain about your involvement with drugs? □ No □ Yes
7. Have you neglected your family because of your use of drugs? □ No □ Yes
8. Have you engaged in illegal activities to obtain drugs? □ No □ Yes
9. Have you ever experienced withdrawal symptoms (i.e., felt sick) when you stopped □ No □ Yes
taking drugs?
10. Have you had medical problems as a result of your drug use (e.g., memory loss, □ No □ Yes
hepatitis, convulsions, bleeding)?
Comments:
Scoring
Score 1 point for each “Yes,” except for question 3, for which a “No” receives 1 point.
DAST Score: __________
Interpretation of Score:
Score Degree of Problems Related to Drug Abuse Suggested Action
0 No problems reported None at this time
1–2 Low level Monitor, reassess at a later date
3–5 Moderate level Further investigation
6–8 Substantial level Intensive assessment
9–10 Severe level Intensive assessment
Adapted with permission.5,6
5-20
Medications for Opioid Use Disorder TIP 63
DSM-5 Opioid Use Disorder Checklist7
Patient’s Name: ___________________________________________________________ Date of Birth: ______________________
Worksheet for DSM-5 Criteria for Diagnosis of Opioid Use Disorder
DIAGNOSTIC CRITERIA
(Opioid use disorder requires that at least 2 criteria be
met within a 12-month period.)
MEETS
CRITERIA?
Yes OR No NOTES/SUPPORTING INFORMATION
1. Opioids are often taken in larger amounts or over
a longer period of time than intended.
2. There is a persistent desire or unsuccessful efforts
to cut down or control opioid use.
3. A lot of time is spent in activities necessary to
obtain the opioid, use the opioid, or recover from
its effects.
4. Craving, or a strong desire to use opioids.
5. Recurrent opioid use resulting in failure to fulfll
major role obligations at work, school, or home.
6. Continued opioid use despite having persistent or
recurrent social or interpersonal problems caused
or exacerbated by the effects of opioids.
7. Important social, occupational, or recreational
activities are given up or reduced because of
opioid use.
8. Recurrent opioid use in situations in which it is
physically hazardous.
9. Continued use despite knowledge of having a
persistent or recurrent physical or psychological
problem that is likely to have been caused or
exacerbated by opioids.
10. Tolerance,* as defned by either of the following:
(a) a need for markedly increased amounts of
opioids to achieve intoxication or desired effect
(b) markedly diminished effect with continued use
of the same amount of an opioid
11. Withdrawal,* as manifested by either of the
following:
(a) the characteristic opioid withdrawal syndrome
(b) the same (or a closely related) substance is
taken to relieve or avoid withdrawal symptoms
*This criterion is not met for individuals taking opioids solely under appropriate medical supervision.
Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms
Signed: _____________________________________________________ Date: _______________________
5-21
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Heaviness of Smoking Index
Ask these two questions of current or recent smokers:
1. How soon after waking do you smoke your frst cigarette?
• Within 5 minutes (3 points)
• 5–30 minutes (2 points)
• 31–60 minutes (1 point)
• 61 or more minutes (no points)
2. How many cigarettes a day do you smoke?
• 10 or less (no points)
• 11–20 (1 point)
• 21–30 (2 points)
• 31 or more (3 points)
Total score: 1 to 2 points = very low dependence; 3 points = low to moderate dependence; 4 points =
moderate dependence; 5 or more points = high dependence
Adapted with permission.8
NIAAA Single-Item Screener
How many times in the past year have you had fve or more drinks in a day (four drinks for women
and all adults older than age 65)?
A response of one or more times is considered a positive screen. Patients who screen positive should
have an assessment for alcohol use disorder.
Adapted with permission.9
5-22
Medications for Opioid Use Disorder TIP 63
Opioid Overdose: Risk, Prevention, Identifcation, and Response
Overdose Risk
• Using heroin (possibly mixed with illicitly manufactured fentanyl or fentanyl analogs)
• Using prescription opioids that were not prescribed
• Using prescription opioids more frequently or at higher doses than prescribed
• Using opioids after a period of abstinence or reduced use (e.g., after medically supervised withdrawal
or incarceration)
• Using opioids with alcohol, benzodiazepines, or both
Overdose Prevention
• Don’t use opioids that were not prescribed.
• Take medications only as prescribed.
• Don’t use drugs when you are alone.
• Don’t use multiple substances at once.
• Have naloxone available and make sure others know where it is and how to use it.
• Use a small “test dose” if returning to opioid use after a period of abstinence, if the substance appears
altered or has been acquired from an unfamiliar source. Beware: This doesn’t guarantee safety; illicitly
manufactured fentanyl or other substances may be present in the drug, and any use may be fatal.
Overdose Identifcation
• Fingernails or lips are blue or purple.
• Breathing or heartbeat is slow or stopped.
• The person is vomiting or making gurgling noises.
• The person can’t be awakened or is unable to speak.
Overdose Response
• Call 9-1-1.
• Administer naloxone (more than one dose may be needed to restore adequate spontaneous breathing).
• Perform rescue breathing. If certifed to provide cardiopulmonary resuscitation, perform chest
compressions if there is no pulse.
• Put the person in the “recovery position,” on his or her side and with the mouth facing to the side to
prevent aspiration of vomit, if he or she is breathing independently.
• Stay with the person until emergency services arrive. Naloxone’s duration of action is 30–90 minutes.
The person should be observed after this time for a return of opioid overdose symptoms.
Adapted from material in the public domain.10
5-23
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Physical Signs of Opioid Withdrawal and Time to Onset
STAGE GRADE
PHYSICAL
SIGNS/SYMPTOMS
Early Withdrawal
Short-acting opioids: 8–24 hours after last use
Long-acting opioids: Up to 36 hours after last use
Grade 1 Lacrimation, rhinorrhea, or both
Diaphoresis
Yawning
Restlessness
Insomnia
Early Withdrawal
Short-acting opioids: 8–24 hours after last use
Long-acting opioids: Up to 36 hours after last use
Grade 2 Dilated pupils
Piloerection
Muscle twitching
Myalgia
Arthralgia
Abdominal pain
Fully Developed Withdrawal
Short-acting opioids: 1–3 days after last use
Long-acting opioids: 72–96 hours after last use
Grade 3 Tachycardia
Hypertension
Tachypnea
Fever
Anorexia or nausea
Extreme restlessness
Fully Developed Withdrawal
Short-acting opioids: 1–3 days after last use
Long-acting opioids: 72–96 hours after last use
Grade 4 Diarrhea, vomiting, or both
Dehydration
Hyperglycemia
Hypotension
Curled-up position
Total duration of withdrawal:
• Short-acting opioids: 7–10 days.
• Long-acting opioids: 14 days or more.
Signs of Opioid Intoxication
Physical Findings
Drowsy but arousable
Sleeping intermittently (“nodding off”)
Constricted pupils
Mental Status Findings
Slurred speech
Impaired memory or concentration
Normal to euphoric mood
Single-Item Drug Screener
How many times in the past year have you
used an illegal drug or used a prescription
medication for nonmedical reasons?
(A positive screen is 1 or more days.)
Reprinted with permission.11
5-24
Medications for Opioid Use Disorder TIP 63
Substance Misuse and SUD Screening
Substance misuse screening
Negative Positive
Reinforce
healthy behavior
Assess substance use
and comorbidities
Substance misuse Substance
use disorder
Brief counseling Brief counseling and
treatment referral
Monitoring/follow up -
Consider
medication
If misuse continues, negotiate
a plan and refer to treatment
Ongoing assessment
and support
Adapted with permission.12
5-25
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
TAPS Tool Part I
Directions: The TAPS Tool Part 1 is a 4-item screening for tobacco use, alcohol use, prescription medication
misuse, and illicit substance use in the PAST YEAR. Question 2 should be answered by males, and Question 3
should be answered by females. Each of the four multiple-choice items has fve possible responses to choose
from. Check the box to select your answer.
In the PAST 12 MONTHS:
1. How often have you used any tobacco product (for example, cigarettes, ecigarettes, cigars, pipes, or smokeless
tobacco)?
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
2. How often have you had 5 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass
of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by males.)
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
3. How often have you had 4 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass
of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by females.)
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
4. How often have you used any drugs including marijuana, cocaine or crack, heroin, methamphetamine (crystal meth),
hallucinogens, or ecstasy/MDMA?
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
5. How often have you used any prescription medications just for the feeling, more than prescribed, or that were not
prescribed for you? Prescription medications that may be used this way include opiate pain relievers (for example,
OxyContin, Vicodin, Percocet, or methadone), medications for anxiety or sleeping (for example, Xanax, Ativan, or
Klonopin), or medications for ADHD (for example, Adderall or Ritalin).
□ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily
5-26
Medications for Opioid Use Disorder TIP 63
TAPS Tool Part 2
Directions: The TAPS Tool Part 2 is a brief assessment for tobacco use, alcohol use, illicit substance use, and
prescription medication misuse in the PAST 3 MONTHS ONLY. Each of the following questions and subquestions
has two possible answers, yes or no. Check the box to select your answer.
In the PAST 3 MONTHS:
1. Did you smoke a cigarette containing tobacco? □ Yes □ No
If “Yes,” answer the following questions:
• Did you usually smoke more than 10 cigarettes each day?
• Did you usually smoke within 30 minutes after waking?
□ Yes
□ Yes
□ No
□ No
2. Did you have a drink containing alcohol? □ Yes □ No
If “Yes,” answer the following questions:
• Did you have 4 or more drinks containing alcohol in a day?* □ Yes □ No
(Note: This question should only be answered by females.)
• Did you have 5 or more drinks containing alcohol in a day?* □ Yes □ No
(Note: This question should only be answered by males.)
• Have you tried and failed to control, cut down, or stop drinking?
• Has anyone expressed concern about your drinking?
□ Yes
□ Yes
□ No
□ No
3. Did you use marijuana (hash, weed)? □ Yes □ No
If “Yes,” answer the following questions:
• Have you had a strong desire or urge to use marijuana at least once a week or more often? □ Yes □ No
• Has anyone expressed concern about your use of marijuana? □ Yes □ No
4. Did you use cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No
If “Yes,” answer the following questions:
• Did you use cocaine, crack, or methamphetamine (crystal meth) at least once a week or more often? □ Yes □ No
• Has anyone expressed concern about your use of cocaine, crack, or methamphetamine (crystal
meth)? □ Yes □ No
5. Did you use heroin? □ Yes □ No
If “Yes,” answer the following questions:
• Have you tried and failed to control, cut down, or stop using heroin? □ Yes □ No
• Has anyone expressed concern about your use of heroin? □ Yes □ No
6. Did you use a prescription opiate pain reliever (for example Percocet or Vicodin) not as □ Yes □ No
prescribed or that was not prescribed for you?
If “Yes,” answer the following questions:
• Have you tried and failed to control, cut down, or stop using an opiate pain reliever? □ Yes □ No
• Has anyone expressed concern about your use of an opiate pain reliever? □ Yes □ No
*One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor.
Continued on next page
5-27
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
7. Did you use medication for anxiety or sleep (for example, Xanax, Ativan, or Klonopin)
not as prescribed or that was not prescribed for you?
If “Yes,” answer the following questions:
• Have you had a strong desire or urge to use medications for anxiety or sleep at least once
a week or more often?
• Has anyone expressed concern about your use of medication for anxiety or sleep?
□ Yes
□ Yes
□ Yes
□ No
□ No
□ No
8. Did you use medication for ADHD (for example, Adderall or Ritalin) not as prescribed
or that was not prescribed for you?
If “Yes,” answer the following questions:
• Did you use a medication for ADHD (for example, Adderall or Ritalin) at least once a week or
more often?
• Has anyone expressed concern about your use of medication for ADHD (for example, Adderall
or Ritalin)?
□ Yes
□ Yes
□ Yes
□ No
□ No
□ No
9. Did you use any other illegal or recreational drugs (for example, ecstasy, molly, GHB, □ Yes □ No
poppers, LSD, mushrooms, special K, bath salts, synthetic marijuana [“spice”], whip-its)?
If “Yes,” answer the following question:
• What were the other drug(s) you used? (write in response)
The complete tool is available online (https://cde.drugabuse.gov/instrument/29b23e2e-e266-f095-e050-bb89ad43472f).
Adapted from material in the public domain.13
Two-Item Drug Use Disorder Screener for Primary Care Clinics Serving U.S. Veterans
Question 1: How many days in the past 12 months have you used drugs other than alcohol?
(A positive screen is 7 or more days.) If <7, proceed with Question 2.
Question 2: How many days in the past 12 months have you used drugs more than you meant to?
(A positive screen is 2 or more days.)
Adapted with permission.14
5-28
Medications for Opioid Use Disorder TIP 63
Urine Drug Testing Window of Detection15,16
DRUG POSITIVE TEST
WINDOW OF
DETECTION* COMMENTS
Amphetamine;
methamphetamine;
3,4-methylenedioxy-
methamphetamine
Amphetamine 1–2 days False positives w/ bupropion,
chlorpromazine, desipramine, fuoxetine,
labetalol, promethazine, ranitidine,
pseudoephedrine, trazadone, and
other common medications. Confrm
unexpected positive results with the
laboratory.
Barbiturates Barbiturates Up to 6 weeks N/A
Benzodiazepines Benzodiazepines 1–3 days; up to 6
weeks with heavy
use of long-acting
benzodiazepines
Immunoassays may not be sensitive
to therapeutic doses, and most
immunoassays have low sensitivity to
clonazepam and lorazepam. Check with
your laboratory regarding sensitivity and
cutoffs. False positives with sertraline or
oxaprozin.
Buprenorphine Buprenorphine 3–4 days Will screen negative on opiate screen.
Tramadol can cause false positives. Can
be tested for specifcally.
Cocaine Cocaine,
benzoylecgonine
2–4 days; 10–22
days with heavy
use
N/A
Codeine Morphine,
codeine,
high-dose
hydrocodone
1–2 days Will screen positive on opiate
immunoassay.
Fentanyl Fentanyl 1–2 days Will screen negative on opiate screen.
Can be tested for specifcally. May not
detect all fentanyl-like substances.17
Heroin Morphine,
codeine
1–2 days Will screen positive on opiate
immunoassay. 6-monoacetylmorphine, a
unique metabolite of heroin, is present in
urine for about 6 hours. Can be tested for
specifcally to distinguish morphine from
heroin, but this is rarely clinically useful.
Hydrocodone Hydrocodone,
hydromorphone
2 days May screen negative on opiate
immunoassay. Can be tested for
specifcally.
Hydromorphone May not be
detected
1–2 days May screen negative on opiate
immunoassay. Can be tested for
specifcally.
Continued on next page
5-29
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Methadone
Comfort
Zone
Serum
Level
0 2 4 6 8 10 12 14 16 18 20 22 24
Opioid Overmedication Signs:
Pinpoint pupils, drowsy or nodding off, listless mental status, itching/scratching,
fushing, decreased body temperature, slowed heartbeat and/or respirations
Opioid Withdrawal—Subjective Symptoms:
Drug craving, anxious feelings or depression, irritability, fatigue, insomnia, hot/cold
fashes, aching muscles/joints, nausea, disorientation, restlessness
Severe Opioid Withdrawal—Objective Signs:
Dilated pupils, illicit opioid use, “goose fesh,” perspiring, shaking, diarrhea, vomiting, runny
nose, sneezing, yawning, fever, hypertension, increased heartbeat and/or respirations
Peak
Trough
No Illicit Opioid Use
No Withdrawal or Overmedication
Hours
Urine Drug Testing Window of Detection (continued)
DRUG POSITIVE TEST
WINDOW OF
DETECTION* COMMENTS
Marijuana Tetrahydrocan-
nabinol
Infrequent
use of 1–3 days;
chronic use of
up to 30 days
False positives possible with efavirenz,
ibuprofen, and pantoprazole.
Methadone Methadone 2–11 days Will screen negative on opiate screen. Can
be tested for specifcally.
Morphine Morphine,
hydromorphone
1–2 days Will screen positive on opiate
immunoassay. Ingestion of poppy plant/
seed may screen positive.
Oxycodone Oxymorphone 1–1.5 days Typically screens negative on opiate
immunoassay. Can be tested for
specifcally.
*Detection time may vary depending on the cutoff.
Using Signs and Symptoms To Determine Optimal Methadone Level
Adapted with permission.18
5-30
Medications for Opioid Use Disorder TIP 63
Provider Informational, Educational, and Decision-Making Tools
Key Elements of an OBOT Clinic Diversion Control Plan19
New Patients Ongoing Patients
Periodically check the state’s PDMP.
Conduct random urine tests that include
a wide spectrum of opioids—including
morphine, oxycodone, and buprenorphine—and
periodically include buprenorphine metabolites.
This will help monitor response to treatment and
determine whether patients are taking at least
some of their prescribed buprenorphine.
Use unobserved specimen collection to
preserve patient privacy and dignity:
• Do not let patients bring backpacks, jackets, or
other items into the bathroom.
• Do not let others enter bathrooms with patients.
• Temperature test the urine sample.
Use observed specimen collection (obtained by
a staff member of the same gender) or oral fuid
testing if there is reason to suspect tampering or
falsifcation.
Contact patients at random; ask them to bring
in their medication within a reasonable period
(24 to 48 hours) to count the tablets/flms to
ensure that all medication is accounted for.
Provide a limited number of days of medication
per prescription without reflls (e.g., several days
or 1 week per prescription) until the patient has
demonstrated stability and lowered diversion
risk.
Check the state’s PDMP before admission
to determine whether patients are receiving
opioids or benzodiazepine prescriptions from
other providers.
Ask patients to sign a release of information to
speak with the other prescribers. Patients who
are unwilling to sign a release of information are
poor candidates for outpatient treatment.
Review the clinic diversion control policy with
new patients. This should include counseling
patients to:
• Keep buprenorphine locked up and out of
children’s reach.
• Never share medication with anyone.
• Never sell medication to anyone.
• Acknowledge giving or selling medication to
others as illegal.
• Take medication only as prescribed.
• Review, understand, and agree to the
practice’s buprenorphine treatment
agreement before they start.
Prescribe buprenorphine/naloxone when
possible, rather than monoproduct. Exceptions
would include prescribing the monoproduct for
pregnant women with OUD.
Prescribe an adequate but not excessive dose.
Most patients respond to doses at or below
24 mg per day. Carefully evaluate requests
for higher doses and confrm, document, and
assess medication adherence continuously.
5-31
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Key Points of Patient Education
for Buprenorphine
Before starting OUD treatment with buprenorphine,
patients should:
• Tell providers the prescribed and over-the-counter
medications they take, to allow drug interaction
assessment.
• Understand the goal of the frst week of treatment:
To improve withdrawal symptoms without
oversedation.
• Tell providers if they feel sedated or euphoric within
1 to 4 hours after their dose.
• Be given the appropriate buprenorphine
medication guide.
• Know possible side effects, including:
- Headache.
- Dizziness.
- Nausea.
- Vomiting.
- Sweating.
- Constipation.
- Sexual dysfunction.
• Agree to store medication securely and out of the
reach of others.
• Alert providers if they discontinue medications,
start new ones, or change their medication dose.
• Understand that discontinuing buprenorphine
increases risk of overdose death upon return to
illicit opioid use.
• Know that use of alcohol or benzodiazepines with
buprenorphine increases the risk of overdose and
death.
• Understand the importance of informing providers
if they become pregnant.
• Tell providers if they are having a procedure that
may require pain medication.
• Be aware of resources through which to obtain
further education for:
- Themselves (https://store.samhsa.gov/product
/SMA16-4993).
- Their families and friends (https://portal.ct.gov/
DMHAS/Programs-and-Services/Opioid-
Treatment/Medication-Assisted-Treatment).
Key Points of Patient Education
for Methadone
Before starting OUD treatment with methadone,
patients should:
• Be told that the methadone dose is started low
and increased slowly over days and weeks with
monitoring, because it takes 4 or more days for the
body to adjust to a dose change. This is necessary
to avoid the risk of overdose.
• Understand that the goal of the frst weeks of
treatment is to improve withdrawal symptoms
without oversedation. Patients should tell providers
if they feel sedated or high within the frst 4 hours
after their dose.
• Learn the symptoms of methadone intoxication and
how to seek emergency care. The frst 2 weeks of
treatment have the highest risk of overdose.
• Be aware that rescue naloxone does not last very
long, so they should remain in emergency care for
observation if they are treated for opioid overdose.
• Know that concurrent alcohol, benzodiazepine, or
other sedative use with methadone increases the
risk of overdose and death.
• Inform OTP nursing/medical staff about prescribed
and over-the-counter medications and herbs
(e.g., St. John’s wort) they are taking, stopping, or
changing doses of to allow assessment of potential
drug–drug interactions.
• Inform other treating healthcare professionals that
they are receiving methadone treatment.
• Plan to avoid driving or operating heavy machinery
until their dose is stabilized.
• Learn about other possible side effects of
methadone, including dizziness, nausea, vomiting,
sweating, constipation, edema, and sexual
dysfunction.
• Agree to keep take-home doses locked up and
out of the reach of others. Understand that giving
methadone, even small amounts, to others may be
fatal.
• Inform providers if they become pregnant.
• Understand that stopping methadone increases
their risk of overdose death if they return to illicit
opioid use.
5-32
Medications for Opioid Use Disorder TIP 63
Key Points of Patient Education
for Naltrexone
• Do not use any opioids in the 7 to 10 days (for short
acting) or 10 to 14 days (for long acting) before
starting XR-NTX, to avoid potentially serious opioid
withdrawal symptoms. Opioids include:
- Heroin.
- Prescription opioid analgesics (including
tramadol).
- Cough, diarrhea, or other medications that
contain codeine or other opioids.
- Methadone.
- Buprenorphine.
• Seek immediate medical help if symptoms of
allergic reaction or anaphylaxis occur, such as:
- Itching.
- Swelling.
- Hives.
- Shortness of breath.
- Throat tightness.
• Do not try to override the opioid blockade with
large amounts of opioids, which could result in
overdose.
• Understand the risk of overdose from using opioids
near the time of the next injection, after missing a
dose, or after stopping medications.
• Report injection site reactions including:
- Pain.
- Hardening.
- Lumps.
- Blisters.
- Blackening.
- Scabs.
- An open wound.
Some of these reactions could require surgery to
repair (rarely).
• Report signs and symptoms of hepatitis.
• Report depression or suicidal thoughts. Seek
immediate medical attention if these symptoms
appear.
• Seek medical help if symptoms of pneumonia
appear (e.g., shortness of breath, fever).
• Tell providers of naltrexone treatment, as treatment
differs for various types of pneumonia.
• Inform all healthcare professionals of XR-NTX
treatment.
• Report pregnancy.
• Inform providers of any upcoming medical
procedures that may require pain medication.
• Understand that taking naltrexone may result in
diffculty achieving adequate pain control if acute
medical illness or trauma causes severe acute pain.
• Wear medical alert jewelry and carry a medical alert
card indicating you are taking XR-NTX. A patient
wallet card or medical alert bracelet can be ordered
at 1-800-848-4876.
5-33
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Medication Management for Patients With Respiratory or Hepatic Impairment Who
Take Buprenorphine
CONTRAINDICATION/CAUTION MANAGEMENT
Compromised respiratory function
(e.g., chronic obstructive pulmonary
disease, decreased respiratory reserve,
hypoxia, hypercapnia [abnormally
elevated blood levels of carbon dioxide],
preexisting respiratory depression).
Hepatic impairment
Buprenorphine and naloxone are
extensively metabolized by the liver.
Moderate to severe impairment results
in decreased clearance, increased overall
exposure to both medications, and
higher risk of buprenorphine toxicity and
precipitated withdrawal from naloxone.
These effects have not been observed in
patients with mild hepatic impairment.21,22
• Prescribe with caution; monitor closely.
• Warn patients about the risk of using benzodiazepines or
other depressants while taking buprenorphine.20
• Support patients in their attempts to discontinue tobacco
use.
• Mild impairment (Child-Pugh score of 5–6):23
No dose adjustment needed.
• Moderate impairment (Child-Pugh score of 7–9):24
Combination products are not recommended; they may
precipitate withdrawal.
*Use combination products cautiously for maintenance
treatment in patients who’ve been inducted with a
monoproduct;25,26 monitor for signs and symptoms of
buprenorphine toxicity or overdose.27 Naloxone may
interfere with buprenorphine’s effcacy.28,29
• Severe impairment (Child-Pugh score of 10–15):30
Do not use the combination product.31 For monoproduct,
consider halving the starting and titration doses used in
patients with normal liver function; monitor for signs and
symptoms of toxicity or overdose caused by increased
buprenorphine levels.32
*Moderate to severe impairment results in much more reduced clearance of naloxone than of buprenorphine. Nasser et
al.33 found that moderate impairment doubled or tripled exposure (compared with subjects with no or mild impairment)
for both medications. In subjects with severe impairment, buprenorphine exposure was two to three times higher;
naloxone exposure increased more than tenfold.
Adapted from material in the public domain.34
Monitoring Recovery Activities
At medical management visits, do not simply ask about attendance at recovery support meetings; explore the
level of participation and engagement in those activities. Some activities include:
• Finding and working closely with a sponsor.
• “Working” the 12 Steps at 12-Step meetings and with a sponsor.
• Doing service at meetings (e.g., setting up chairs, making coffee, going on a “commitment” to speak at a
meeting in a jail or an inpatient drug and alcohol program).
• Having and frequently attending a regular “home” group.35
Remember this statement from recovery experts A. Thomas McLellan and William White: “Recovery status is
best defned by factors other than medication status. Neither medication-assisted treatment of opioid addiction
nor the cessation of such treatment by itself constitutes recovery. Recovery status instead hinges on broader
achievements in health and social functioning—with or without medication support.”36
5-34
Medications for Opioid Use Disorder TIP 63
OUD Medications: An Overview37,38
CATEGORY BUPRENORPHINE* METHADONE XR-NTX**
A
p
p
ro
p
ri
at
e
p
at
ie
n
ts
Typically for patients with OUD who
are physiologically dependent on
opioids
Typically for patients
with OUD who are
physiologically dependent
on opioids and who meet
federal criteria for OTP
admission
Typically for patients with
OUD who have abstained
from short-acting opioids
for at least 7–10 days and
long-acting opioids for at
least 10–14 days
P
h
ar
m
ac
ol
og
y Opioid receptor partial agonist
Reduces opioid withdrawal and
craving; blunts or blocks euphoric
effects of self-administered illicit
opioids through cross-tolerance
and opioid receptor occupancy.
Opioid receptor agonist
Reduces opioid withdrawal
and craving; blunts or
blocks euphoric effects
of self-administered illicit
opioids through cross-
tolerance and opioid
receptor occupancy.
Opioid receptor
antagonist
Blocks euphoric effects
of self-administered illicit
opioids through opioid
receptor occupancy.
Causes no opioid effects.
P
at
ie
n
t
E
d
u
ca
ti
on
Tell patients:
• That they will need to be in opioid
withdrawal to receive their frst
dose to avoid buprenorphine-
precipitated opioid withdrawal.
• About the risk of overdose with
concurrent benzodiazepine
or alcohol use, with injecting
buprenorphine, and after
stopping the medication.
Tell patients:
• That their dose will start
low and build up slowly
to avoid oversedation; it
takes several days for a
given dose to have its full
effect.
• About overdose risk
in the frst 2 weeks of
treatment, especially
with concurrent
benzodiazepine or
alcohol use, and after
stopping the medication.
Tell patients:
• That they will need to
be opioid free for at
least 7–10 days for short-
acting and at least 10–14
days for long-acting
opioids before their frst
dose to avoid XR-NTX-
precipitated opioid
withdrawal (which may
require hospitalization).
• About the risk of
overdose after stopping
the medication.
A
d
m
in
is
tr
at
io
n
Daily (or off-label less-than-daily
dosing regimens) administration
of sublingual or buccal tablet or
flm. Subdermal implants every 6
months, for up to 1 year, for stable
patients. Monthly subcutaneous
injection of extended-release
formulation in abdominal region for
patients treated with transmucosal
buprenorphine for at least 1 week.
Daily oral administration
as liquid concentrate,
tablet, or oral solution
from dispersible tablet or
powder (unless patients
can take some home).
Every 4 weeks or once-
per-month intramuscular
injection.
P
re
sc
ri
b
in
g
Physicians, NPs, PAs, and, until
October 1, 2023, clinical nurse
specialists, certifed registered
nurse anesthetists, and certifed
nurse midwives need a waiver to
prescribe. Any pharmacy can fll a
prescription for sublingual or buccal
formulations. OTPs can administer/
dispense by OTP physician order
without a waiver.
SAMHSA-certifed OTPs
can provide methadone for
daily onsite administration
or at-home self-
administration for stable
patients.
Physicians, NPs, PAs, and,
until October 1, 2023,
clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed
nurse midwives prescribe
or order administration
by qualifed healthcare
professionals.
*Long-acting buprenorphine implants (every 6 months) for patients on a stable dose of buprenorphine are also
available through implanters and prescribers with additional training and certifcation through the Probuphine REMS
Program. Extended-release buprenorphine monthly subcutaneous injections are available only through prescribers and
pharmacies registered with the Sublocade REMS Program.
**Naltrexone hydrochloride tablets (50 mg each) are also available for daily oral dosing but have not been shown to be
more effective than treatment without medication or placebo because of poor patient adherence.
5-35
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
OUD Medications: Comparison To Guide Shared Decision Making
CATEGORY BUPRENORPHINE METHADONE NALTREXONE
Appropriate Typically for patients Typically for patients Typically for patients with
patients with OUD who are with OUD who are OUD who are abstinent
physiologically dependent physiologically dependent from short-acting opioids
on opioids on opioids and who meet for 7 days and long-acting
federal criteria for OTP opioids for 10–14 days
admission
Outcome: Higher than treatment Higher than treatment For XR-NTX, treatment
Retention in without medication and without OUD medication retention is higher than
treatment treatment with placebo39 and treatment with for treatment without
placebo40 OUD medication and
treatment with placebo,
but treatment retention
with oral naltrexone is no
better than with placebo
or no medication 41 ,42,43
Outcome:
Suppression of
illicit opioid use
Effective Effective Effective
Outcome:
Overdose
mortality
Lower for people in
treatment than for
those not in it
Lower for people in
treatment than for
those not in it
Unknown
Location/ Offce/clinic: Begins daily OTP only: 6–7 days/week Offce/clinic: Varies from
frequency of to weekly, then tailored initially; take-homes are weekly to monthly
offce visits to patient’s needs
OTP: Can treat with
buprenorphine 6–7 days/
allowed based on time
in treatment and patient
progress
week initially; take-homes
are allowed without
the time-in-treatment
requirements of methadone
Who can Physicians, NPs,* PAs, OTP physicians order the Physicians, NPs,* PAs,
prescribe/order? and, until October 1, 2023,
clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed
nurse midwives possessing
a federal waiver can
prescribe and dispense;
can be dispensed by a
community pharmacy or
an OTP
medication; nurses and
pharmacists administer
and dispense it
and, until October 1, 2023,
clinical nurse specialists,
certifed registered nurse
anesthetists, and certifed
nurse midwives
**NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives should check
with their state to determine whether prescribing buprenorphine, naltrexone, or both is within their allowable scope of
practice.
Continued on next page
5-36
Medications for Opioid Use Disorder TIP 63
OUD Medications: Comparison To Guide Shared Decision Making (continued)
CATEGORY BUPRENORPHINE METHADONE NALTREXONE
Administration Sublingual/buccal;
injection implant by
specially trained provider,
and only for stabilized
patients
Oral Oral or intramuscular
(Note: Oral naltrexone
is less effective than the
other OUD medications.)
Misuse/diversion Low in OTPs or other Low in OTPs with directly None
potential settings with observed
dose administration;
moderate for take-
home doses; risk can be
mitigated by providing
take-homes to stable
patients and a diversion
control plan
observed therapy;
moderate for take-
home doses; risk can be
mitigated by a diversion
control plan
Sedation Low unless concurrent
substances are
present (e.g., alcohol,
benzodiazepines)
Low unless dose titration
is too quick or dose is
not adjusted for the
presence of concurrent
substances (e.g., alcohol,
benzodiazepines)
None
Risk of
medication-
induced respira-
tory depression
Very rare; lower than
methadone
Rare, although higher than
buprenorphine; may be
elevated during the frst 2
weeks of treatment or in
combination with other
sedating substances
None
Risk of Can occur if started too None Severe withdrawal is
precipitated prematurely after recent possible if period of
withdrawal use of other opioids abstinence is inadequate
when starting before starting medication
medication
Withdrawal
symptoms on
discontinuation
Present; lower than
methadone if abruptly
discontinued
Present; higher than
buprenorphine if abruptly
discontinued
None
Most common Constipation, vomiting, Constipation, vomiting, Diffculty sleeping, anxiety,
side effects headache, sweating,
insomnia, blurred vision
sweating, dizziness,
sedation
nausea, vomiting, low
energy, joint and muscle
pain, headache, liver
enzyme elevation
XR-NTX: Injection site pain,
nasopharyngitis, insomnia,
toothache
D. Coffa, December 2017 (personal communication). Adapted with permission.
5-37
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
OUD Medications: Formulations44,45
GENERIC/
TRADE NAME FORMULATIONS
ACTION AT THE
RECEPTOR FDA INDICATIONS DOSING REGIMEN
Methadone Orally as liquid Mu-opioid receptor Medically supervised Once daily (also
(Methadose, concentrate, full agonist withdrawal and off-label dosing
Dolophine) tablet, or oral
solution of
powder or
dispersible
tablet
maintenance
treatment of opioid
dependence; additional
formulations FDA-
approved for pain are
not a focus of this TIP
regimens if
appropriate, such
as split dose twice
daily)
Generic Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also
buprenorphine partial agonist dependence; additional alternative off-label
monoproduct formulations FDA-
approved for pain are
not a focus of this TIP
regimens)
Generic
combination
product
(buprenorphine/
naloxone)
Sublingual
tablet, flm
Mu-opioid receptor
partial agonist
combined with
mu-opioid receptor
antagonist;
the latter is
not absorbed
sublingually
Treatment of opioid
dependence
Once daily (also
alternative off-label
regimens)
Buprenorphine/ Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also
naloxone partial agonist dependence alternative off-label
(Zubsolv) combined with
mu-opioid receptor
antagonist;
the latter is
not absorbed
sublingually
regimens)
Buprenorphine/ Buccal flm Mu-opioid receptor Treatment of opioid Once daily (also
naloxone partial agonist dependence alternative off-label
(Bunavail) combined with
mu-opioid receptor
antagonist;
the latter is
not absorbed
sublingually
regimens)
Buprenorphine/ Sublingual flm; Mu-opioid receptor Treatment of opioid Once daily (also
naloxone may also be partial agonist dependence alternative off-label
(Suboxone) administered
buccally
combined with
mu-opioid receptor
antagonist;
the latter is
not absorbed
sublingually
regimens)
Continued on next page
5-38
Medications for Opioid Use Disorder TIP 63
OUD Medications: Formulations (continued)
GENERIC/
TRADE NAME FORMULATIONS
ACTION AT THE
RECEPTOR FDA INDICATIONS DOSING REGIMEN
Buprenorphine
(Probuphine)
Implants Mu-opioid receptor
partial agonist
Maintenance treatment
of opioid dependence
in clinically stable
patients taking 8 mg/
day or less of Suboxone
equivalents
Implants last for
6 months and are
then removed,
after which a
second set can be
inserted
Extended-
release
injection
buprenorphine
(Sublocade)
Subcutaneous
injection in
the abdominal
region
Mu-opioid receptor
partial agonist
Treatment of
moderate-to-severe
OUD among patients
initiated and taking
transmucosal
buprenorphine for at
least 7 days
Monthly
Oral naltrexone
(Naltrexone
hydrochloride)
Oral tablet Mu-opioid receptor
antagonist
Block the effects of
administered opioid
agonists
Once daily (also
alternative off-label
regimens)
XR-NTX (Vivitrol) Intramuscular
injection
Mu-opioid receptor
antagonist
Prevent return to opioid
dependence after
medically supervised
opioid withdrawal
Once monthly by
injection
5-39
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Referring Patients Who Receive OUD Medications to Behavioral Health Therapies
Case
management
Vocational
training
Yes No
Yes No
Is the patient
willing to engage
in additional
behavioral health
therapies?
Is the patient
entering an OTP
for methadone or
intensive treatment?
Offer best advice and
ongoing motivational
interviewing; revisit
offer for behavioral
health therapies.
Counseling, peer
support, and case
management will
likely be provided
through the OTP.
Identify specifc
needs, and refer
appropriately to
one or more of
the following:
Counseling:
Individual, family,
and/or group
Peer support groups:
Alcoholics Anonymous,
Narcotics Anonymous,
SMART Recovery,
buprenorphine groups
Housing,
transportation,
food, legal, and other
support programs
5-40
Medications for Opioid Use Disorder TIP 63
Strategies for Managing Benzodiazepine Use by Patients in OUD Treatment
• Carefully assess the patient’s benzodiazepine use, including:
- Intent of use.
- Source (check the state’s PDMP).
- Amount and route of use.
- Binge use.
- Prior overdoses.
- Harms (e.g., car crashes, criminal acts, sleep trouble).
- Co-use with other substances that further increase risk for respiratory depression and overdose.
- Withdrawal history (e.g., seizures, delirium).
• Also assess the following:
- Psychiatric and medical comorbidity
- Motivation for change
- Psychosocial support system (obtain history from a signifcant other if the patient permits)
• Gauge level of care and setting needed (e.g., residential, outpatient). Inpatient treatment may be best for
patients with poor motivation, limited psychosocial support, serious or complicated comorbidity, or injection
or binge use.
• Coordinate with other prescribers. Some patients may have taken appropriately prescribed benzodiazepines
for years with limited or no evidence of misuse. For such patients, tapering benzodiazepines may be
contraindicated and unrealistic.
• Address comorbid mental disorders (e.g., anxiety, depression) with other medications or psychosocial
treatments, when feasible.
• Provide medically supervised withdrawal from benzodiazepines or refer to specialty care for same.
• Create a treatment plan with built-in conditions (e.g., urine testing, more frequent visits, short medication
supply).
• Frequently review patient progress and objective outcomes, such as:
- Urine drug testing.
- PDMP reports.
- Psychosocial functioning.
- Reports from signifcant others.
• Revise treatment plans as needed, and document the rationale for treatment decisions.
Adapted with permission.46
5-41
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Sample Provider Forms
General forms
Goal-Setting Form
Patient’s Name: ________________________________________________________________ Date: _________________________
GOAL CATEGORY
CURRENT
SITUATION SCORE
10 = major problems
and 0 = no problems
What would need
to change to decrease
this score?
PRIORITY SCORE
10 = highest priority (“I really
want to work on this”) and
1 = lowest priority (“I really do
not want to work on this”)
Opioid use
Other illicit drug use: ______________
Alcohol use
Tobacco use
Physical health
Mental health
Legal/court issues
Finances
Job/employment
Hobbies
Family relations
Partner relations
Supportive drug-free network
Education
Keeping medication safe
(e.g., not giving it away, selling it,
having it stolen)
Other
Other
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
5-42
Medications for Opioid Use Disorder TIP 63
Goal Sheet and Coping Strategies Form
Goals are things you would like to accomplish.
Patient’s Name: _______________________________________________________________ Date: _________________________
3-MONTH 1
GOALS
2
3
6-MONTH 1
GOALS
2
3
1-YEAR 1
GOALS
2
3
List of Triggers to Using Drugs
People To Stay Away From
Places To Stay Away From
Ways To Cope or Manage Stress Without Using Drugs
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
5-43
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
________________________________________________________________________________________________________________
Medical Management Visit Form
Patient’s Name: ___________________________________________________________ ID#____________________________
Date: ____________________ Week#: _________ Dose: ________ mg □ No Show
Heroin/cocaine or other illicit drug use since last visit?
Symptoms or signs that might indicate return to use (e.g., changes in mood, physical appearance)?
Since the last visit, are there any problems with the following:
If yes, explain
Drug Use □ Yes □ No
Alcohol Use □ Yes □ No
Psychiatric □ Yes □ No
Medical □ Yes □ No
Employment □ Yes □ No
Social/Family □ Yes □ No
Legal □ Yes □ No
Any new problem to add to Treatment Plan Review? □ Yes □ No
Plan to address any new problem _________________________________________________________________________________
Participation in Narcotics Anonymous or Alcoholics Anonymous since last visit? □ Yes □ No
Length of Session: ________________ Healthcare Professional Signature: ___________________________________________
D. Fiellin, December 3, 2016 (personal communication). Adapted with permission.
5-44
Medications for Opioid Use Disorder TIP 63
Patient Urine Drug Screen and Medication Count Monitoring Form
Patient’s Name: ______________________________________________________ Dates To Be Called: ____________________
Called for:
□ Urine Drug Screen
□ Medication Count at □Offce or □Pharmacy FOR: _____________________________________________________________
□ Buprenorphine/Naloxone
□ Other (list drug: ___________________________, ___________________________, ___________________________)
Documentation of Phone Call to Patient
Patient was called at _____________________________ (insert phone #) on ____________________ (date) at
_____:_____ (time) and informed of monitoring required (described above) within the next _______ hours.
Check One:
□ I spoke with patient
□ Message left on answering machine/voicemail
□ Message left with ________________________________________________
□ Other __________________________________________________________
Signature of Staff Member Making Phone Call: _______________________________________________________
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
5-45
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
________________________________________________
Pharmacy Tablet/Film Count Form
(Note: Before sending this form, discuss with the pharmacist frst to explain goals and procedures and to ensure
agreement and understanding.)
Date: ___________________
To: Pharmacists @ ________________________________________ Pharmacy
From: Healthcare Provider: ____________________________________________
Clinic Address: _________________________________________________
Phone Number: ________________________________________________
My patient, __________________________________, is starting offce-based buprenorphine treatment for opioid
dependence.
As part of monitoring this treatment, we ask the patient to do buprenorphine tablet/flm counts at random times (we
call the patient when it’s time for a pill/flm count).
The above-named patient lives much closer to your pharmacy than to our treatment clinic. It would be a big help to
me and this patient if you would be able to perform periodic tablet/flm counts on his/her buprenorphine and then fax
this form to us.
On the days we call the patient for a random tablet/flm count, the patient would come to your pharmacy with his or
her pill bottle. When we call the patient to go for a random tablet/flm count, we will fax this form to you. We would
appreciate if you could record the tablet/flm count results on this form and fax it back to us the same day. This would
be a real help to me in monitoring my patient’s treatment and also a great service to the patient.
Thank you very much for your help with this! Sincerely,
Signature
Buprenorphine/naloxone formulation: _________________________________________
Dose per tablet/flm: _______________
Total # of tablets/flms remaining in bottle: ______________ Fill date on bottle: ___________________
Total # of tablets/flms dispensed on fll date: ____________ Tablet/flm count correct? □Yes □No
Please fax this back to: _____________________________________
Thank You!
M. Lofwall, February 27, 2017 (personal communication). Adapted with permission.
5-46
Medications for Opioid Use Disorder TIP 63
Standard Consent to Opioid Maintenance Treatment Form for OTPs
CONSENT TO PARTICIPATE IN METHADONE OR BUPRENORPHINE TREATMENT
Patient’s Name: _____________________________________________________ Date: ________________
I authorize and give voluntary consent to _________________________________ [insert name of program]
to dispense and administer medications—including methadone or buprenorphine—to treat my opioid
use disorder. Treatment procedures have been explained to me, and I understand that I should take my
medication at the schedule determined by the program physician, or his/her designee, in accordance
with federal and state regulations.
I understand that, like all other medications, methadone or buprenorphine can be harmful if not taken
as prescribed. It has been explained to me that I must safeguard these medications and not share them
with anyone because they can be fatal to children and adults if taken without medical supervision.
I also understand that methadone and buprenorphine produce physical opioid dependence.
Like all medications, they may have side effects. Possible side effects, as well as alternative treatments
and their risks and benefts, have been explained to me.
I understand that it is important for me to inform any medical and psychiatric provider who may treat
me that I am enrolled in an opioid treatment program. In this way, the provider will be aware of all the
medications I am taking, can provide the best possible care, and can avoid prescribing medications that
might affect my treatment with methadone or buprenorphine or my recovery.
I understand that I may withdraw voluntarily from this treatment program and discontinue the use of
these medications at any time. If I choose this option, I understand I will be offered medically supervised
withdrawal.
For women of childbearing age: Pregnant women treated with methadone or buprenorphine have
better outcomes than pregnant women not in treatment who continue to use opioid drugs. Newborns
of mothers who are receiving methadone or buprenorphine treatment may have opioid withdrawal
symptoms (i.e., neonatal abstinence syndrome). The delivery hospital may require babies who are
exposed to opioids before birth to spend a number of days in the hospital for monitoring of withdrawal
symptoms. Some babies may also need medication to stop withdrawal. If I am or become pregnant, I
understand that I should tell the medical staff of the OTP right away so I can receive or be referred to
prenatal care. I understand that there are ways to maximize the healthy course of my pregnancy while I
am taking methadone or buprenorphine.
Signature of Patient: ___________________________________________________ Date of Birth: ________________
Date: ________________ Witness: ______________________________________________________________________
Adapted from material in the public domain.47
5-47
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Buprenorphine Forms
Buprenorphine Diversion Control Policy
XYZ Medical Practice
Offce-Based Opioid Use Disorder Policy and Procedure Manual
Policy Title: Diversion Control for Patients Prescribed Transmucosal (Sublingual) Buprenorphine
Effective Date: ______________________ (Month, Day, Year)
This Diversion Control Policy is provided for educational and informational purposes only. It is intended to offer healthcare
professionals guiding principles and policies regarding best practices in diversion control for patients who are prescribed
buprenorphine. This policy is not intended to establish a legal or medical standard of care. Healthcare professionals should
use their personal and professional judgment in interpreting these guidelines and applying them to the particular circum-
stances of their individual patients and practice arrangements. The information provided in this Policy is provided “as is”
with no guarantee as to its accuracy or completeness.
Preamble: Healthcare professionals can now treat up to 275 patients with buprenorphine. This increased access may contrib-
ute to increased diversion, misuse, and related harms. Signs that a patient is misusing or diverting buprenorphine include (1)
missed appointments; (2) requests for early reflls because pills were lost, stolen, or other reasons; (3) urine screens negative
for buprenorphine, positive for opioids; (4) claims of being allergic or intolerant to naloxone and requesting monotherapy;
(5) nonhealing or fresh track marks; or (5) police reports of selling on the streets. Likewise, there are a range of reasons for
diversion and misuse (e.g., diverting to family/friends with untreated opioid addiction with the intent of trying to “help”
convince them to also get treatment; diverting to family/friends on a treatment waiting list; selling some or all of the
medication to pay off old drug debts/purchase preferred opioid of misuse/pay for treatment in places where there are
inadequate addiction treatment professionals taking private insurance or Medicaid for such reasons as inadequate reim-
bursement/no reimbursement/burdensome prior authorization process).
The safety and health of patients and others in the community could be at risk if misuse and diversion are not addressed
proactively throughout treatment. The reputation of XYZ Medical Practice may also be put at risk.
Defnitions: Diversion is defned as the unauthorized rerouting or misappropriation of prescription medication to someone
other than for whom it was intended (including sharing or selling a prescribed medication); misuse includes taking medica-
tion in a manner, by route or by dose, other than prescribed.48
Purpose: Misuse and diversion should be defned and discussed with patients at the time of treatment entry; periodically
throughout treatment, particularly when there have been returns to illicit drug use; and when suspected (e.g., incorrect
buprenorphine pill/flm count) or confrmed. These procedures will establish the steps to be taken to prevent, monitor, and
respond to misuse and diversion of buprenorphine. The response should be therapeutic and matched to the patients’ needs,
as untreated opioid use disorder and treatment dropout/administrative discharges may lead to increased patient morbidity
and mortality and further use of diverted medications or illicit opioids associated with overdose death.
Procedures for Prevention:
• Use buprenorphine/naloxone combination products when medically indicated and cost is not an issue. Reserve
the daily buprenorphine monoproducts for pregnant patients and patients who could not afford treatment if the
combination product were required, who have a history of stability in treatment and low diversion risk, or who have
arrangements for observed dosing. Buprenorphine monoproducts are recommended for pregnant women.
• Counsel patients on safe storage of, and nonsharing of, medications. Patients must agree to safe storage of their
medication. This is even more critical if there are children in the home where the patient lives. Counsel patients
about acquiring locked devices and avoiding storage in parts of the home frequented by visitors (e.g., do not
recommend storage in the kitchen or common bathrooms). Proactively discuss how medication should be stored and
transported when traveling to minimize risk of unintended loss.
• Counsel patients on taking medication as instructed and not sharing medication. Explicitly explain to patients the
defnitions of diversion and misuse, with examples. Patients are required to take medication as instructed by the
healthcare professional; for example, they may not crush or inject the medication.
• Check the prescription drug monitoring program for new patients and check regularly thereafter. Prescription drug
monitoring program reports can be a useful resource when there is little history available or when there is a concern
based on observation. Check for prescriptions that interact with buprenorphine and for other buprenorphine
prescribers.
5-48
Medications for Opioid Use Disorder TIP 63
• Prescribe a therapeutic dose that is tailored to the patient’s needs. Do not routinely provide an additional supply
“just in case.” Question patients who say they need a signifcantly higher dose, particularly when they are already at
24 mg per day of buprenorphine equivalents.
• Make sure the patient understands the practice’s treatment agreement and prescription policies. The XYZ Medical
Practice’s treatment agreement and other documentation are clear about policies regarding number of doses in
each prescription, reflls, and rules on “lost” prescriptions. Review the policies in person with the patient. Offer an
opportunity for questions. Patient and provider must sign the agreement. Review the policies again with the patient
at subsequent appointments. See Sample Buprenorphine Treatment Agreement or Sample XR-NTX Treatment
Agreement as needed.
Procedures for Monitoring:
• Request random urine tests. The presence of buprenorphine in the urine indicates that the patient has taken some
portion of the prescribed dose. Absence of buprenorphine in the urine supports nonadherence. Testing for bu-
prenorphine metabolites (which are present only if buprenorphine is metabolized) should periodically be included to
minimize the possibility that buprenorphine is added directly to the urine sample. Dipstick tests can be subverted or
replaced. A range of strategies can be used to minimize falsifed urine collections, including (1) observed collection;
(2) disallowing carry-in items (e.g., purses, backpacks) in the bathroom; (3) turning off running water and coloring
toilet water to eliminate the possibility of dilution; (4) monitoring the bathroom door so that only one person can go
in; and (5) testing the temperature of the urine immediately after voiding.
• Schedule unannounced pill/flm counts. Periodically ask patients who are at high risk at initial or subsequent appoint-
ments to bring in their medication containers for a pill/flm count.
• With unannounced monitoring (both pill/flm counts and urine tests), the patient is contacted and must appear within
a specifed time period (e.g., 24 hours) after the phone call. If the patient doesn’t show, then the provider should
consider this as a positive indicator of misuse or diversion.
• Directly observe ingestion. Patients take medication in front of the healthcare professional or another qualifed
clinician and are observed until the medication dissolves in the mouth (transmucosal [sublingual or buccal] absorp-
tion). Patients who are having diffculty adhering to their buprenorphine can have their medication provided under
direct observation in the offce for a designated frequency (e.g., three times/week).
• Limit medication supply. When directly observed doses in the offce are not practical, short prescription time spans
can be used (e.g., weekly, 3 days at a time).
Procedures To Respond to Misuse or Diversion: Misuse or diversion doesn’t mean automatic discharge from
the practice. However, it will require consideration of one or more of the following procedures:
• Evaluate the misuse and diversion. For instance, describe the incident of misuse (e.g., “the patient took the pre-
scribed dose on three or more occasions by intravenous route immediately after starting treatment, stating that she
believed the dose would not be adequate by sublingual route; she has just initiated treatment”) or diversion (“the
patient gave half of dose to his wife, who is still using heroin and was withdrawing, because he did not want her to
have to buy heroin off the street; she is on a waiting list for treatment”) and tailor the response to the behavior (e.g.,
reeducation of the patient on buprenorphine pharmacology in the frst example above; assistance with treatment
entry for the spouse in the second example). Reassess the treatment plan and patient progress. Strongly consider
smaller supplies of medication and supervised dosing for any patient who is taking medication intravenously or in-
tranasally or diverting, regardless of reason. Treatment structure may need to be increased, including more frequent
appointments, supervised administration, and increased psychosocial support.
• Intensify treatment or level of care, if needed. Some patients may require an alternative treatment setting or pharma-
cotherapy such as methadone. The clinician will discuss these alternatives with the patient to ensure optimal patient
outcome. This should be discussed at treatment onset so the patient is aware of the consequences of misuse and
diversion.
• Document and describe the misuse and diversion incident. Also document the clinical thinking that supports the
clinical response, which should be aimed at minimizing risk of diversion and misuse and treating the patient’s opioid
use disorder at the level of care needed.
Policy adapted from ASAM’s Offce-Based Opioid Use Disorder Policy and Procedure Manual, which is updated periodically;
the most current version is available online (www.asam.org/docs/default-source/advocacy/sample-diversion-policy
.pdf?sfvrsn=6).
Adapted with permission.49
5-49
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Buprenorphine Induction and Maintenance Appropriate Use Checklists
Continued on next page
5-50
Medications for Opioid Use Disorder TIP 63
Available online (www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2017-01-23_Appropriate_Use_Checklist.pdf).
Reprinted from material in the public domain.50
5-51
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Buprenorphine Treatment Agreement
This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care.
Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances
of their individual patients and practice arrangements. The information provided in this form is provided “as is”
with no guarantee as to its accuracy or completeness.
TREATMENT AGREEMENT
I agree to accept the following treatment contract for buprenorphine offce-based opioid addiction treatment:
1. The risks and benefts of buprenorphine treatment have been explained to me.
2. The risks and benefts of other treatment for opioid use disorder (including methadone, naltrexone, and
nonmedication treatments) have been explained to me.
3. I will keep my medication in a safe, secure place away from children (for example, in a lockbox). My plan is to
store it [describe where and how _____________________________________________________________________].
4. I will take the medication exactly as my healthcare provider prescribes. If I want to change my medication dose,
I will speak with my healthcare provider frst. Taking more medication than my healthcare provider prescribes
or taking it more than once daily as my healthcare provider prescribes is medication misuse and may result in
supervised dosing at the clinic. Taking the medication by snorting or by injection is also medication misuse and
may result in supervised dosing at the clinic, referral to a higher level of care, or change in medication based on
my healthcare provider’s evaluation.
5. I will be on time to my appointments and respectful to the offce staff and other patients.
6. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical
problems.
7. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider
without consulting my buprenorphine prescriber.
8. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance
so that my pain will be adequately treated.
9. If I miss an appointment or lose my medication, I understand that I will not get more medication until my next
offce visit. I may also have to start having supervised buprenorphine dosing.
10. If I come to the offce intoxicated, I understand that my healthcare provider will not see me, and I will not receive
more medication until the next offce visit. I may also have to start having supervised buprenorphine dosing.
11. I understand that it’s illegal to give away or sell my medication; this is diversion. If I do this, my treatment will no
longer include unsupervised buprenorphine dosing and may require referral to a higher level of care, supervised
dosing at the clinic, and/or a change in medication based on my healthcare provider’s evaluation.
12. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in
treatment termination from the clinic.
13. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will
count as a positive drug test.
14. I understand that I will be called at random times to bring my medication container into the offce for a pill or
flm count. Missing medication doses could result in supervised dosing or referral to a higher level of care at this
clinic or potentially at another treatment provider based on my individual needs.
15. I understand that initially I will have weekly offce visits until I am stable. I will get a prescription for 7 days of
medication at each visit.
16. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine
drug tests in a row. I will then get a prescription for 14 days of medication at each visit.
17. I will go back to weekly visits if I have a positive drug test. I can go back to visits every 2 weeks when I have two
negative drug tests in a row again.
18. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me.
19. I understand that people have died by mixing buprenorphine with alcohol and other drugs like benzodiazepines
(drugs like Valium, Klonopin, and Xanax).
Continued on next page
5-52
Medications for Opioid Use Disorder TIP 63
20. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to comply
with my healthcare provider’s recommendations for additional counseling and/or for help with other problems.
21. I understand that there is no fxed time for being on buprenorphine and that the goal of treatment is for me to
stop using all illicit drugs and become successful in all aspects of my life.
22. I understand that I may experience opioid withdrawal symptoms when I stop taking buprenorphine.
23. I have been educated about the other two FDA-approved medications used for opioid dependence treatment,
methadone and naltrexone.
24. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting
buprenorphine treatment and been informed about methods for preventing pregnancy.
Other specifc items unique to my treatment include:
Patient’s Name (print): _____________________________________________________
Patient’s Signature: ________________________________________________________ Date: ____________________
This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is
updated periodically; the most current version of the agreement is available online (www.asam.org/docs
/default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn
=bd4675c2_0).
Adapted with permission.51
5-53
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Naltrexone forms
Key Techniques for Reducing Injection Site Reactions52
To reduce severe injection site reactions when administering XR-NTX via intramuscular injection, use
the following techniques:
• Use one of the administration needles provided with the XR-NTX kit to ensure that the
injection reaches the gluteal muscle. Use the 2-inch needle for patients who have more subcuta-
neous adipose tissue. Use the 1.5-inch needle for patients with less subcutaneous adipose tissue.
Either needle is appropriate for use with patients who have average amounts of subcutaneous
adipose tissue.
• Use aseptic technique when administering intramuscularly. Using a circular motion, clean the
injection site with an alcohol swab. Let the area dry before administering the injection. Do not
touch this area again before administration.
• Use proper deep intramuscular injection technique into the gluteal muscle. XR-NTX must not
be injected intravenously, subcutaneously, or into adipose tissue. Accidental subcutaneous injection
may increase the risk of severe injection site reactions.
− Administer the suspension by deep intramuscular injection into the upper outer quadrant
of gluteal muscle, alternating buttocks per monthly injection.
− Remember to aspirate for blood before injection. If blood aspirates or the needle clogs, do
not inject. Change to the spare needle provided in the package and administer into an adjacent
site in the same gluteal region, again aspirating for blood before injection.
− Inject the suspension in a smooth, continuous motion.
A patient counseling tool is available to help you counsel your patients before administration about
the serious risks associated with XR-NTX.
The above information is a selection of key safety information about the XR-NTX injection. For
complete safety information, refer to the directions for use and the prescribing information provided
in the medication kit. You can also obtain this information online (www.vivitrolrems.com) or by calling
1-800-VIVITROL.
Available online (www.vivitrolrems.com/content/pdf/patinfo-injection-poster.pdf).
5-54
Medications for Opioid Use Disorder TIP 63
Patient Counseling Tool for XR-NTX
Risk of sudden opioid withdrawal during initiation and re-initiation of VIVITROL
Using any type of opioid including street drugs, prescription pain medicines, cough, cold or diarrhea medicines
that contain opioids, or opioid dependence treatments buprenorphine or methadone, in the 7 to 14 days before
starting VIVITROL may cause severe and potentially dangerous sudden opioid withdrawal.
Risk of opioid overdose
Patients may be more sensitive to the effects of lower amounts of opioids:
Patients should tell their family and people close to them about the increased sensitivity to opioids and the
risk of overdose even when using lower doses of opioids or amounts that they used before treatment. Using
large amounts of opioids, such as prescription pain pills or heroin, to overcome effects of VIVITROL can lead to
serious injury, coma, and death.
Risk of severe reactions at the injection site
Remind patients of these possible symptoms at the injection site:
Some of these injection site reactions have required surgery.
Tell your patients to contact a healthcare provider if they have any reactions at the injection site.
Risk of liver injury, including liver damage or hepatitis
Remind patients of the possible symptoms of liver damage or hepatitis.
Patients may not feel the therapeutic effects of opioid-containing medicines for pain, cough or
cold, or diarrhea while taking VIVITROL.
Patients should carry written information with them at all times to alert healthcare providers that they are
taking VIVITROL, so they can be treated properly in an emergency.
A Patient Wallet Card or Medical Alert Bracelet can be ordered from: 1-800-848-4876, Option #1.
Patient Counseling Tool
VIVITROL® (naltrexone for extended-release injectable suspension)
• After stopping opioids (detoxifcation) • If a dose of VIVITROL is missed
• When the next VIVITROL dose is due • After VIVITROL treatment stops
• Intense pain • Blisters
• The area feels hard • Open wound
• Large areas of swelling • Dark scab
• Lumps
• Stomach area pain lasting more than a few days • Yellowing of the whites of eyes
• Dark urine • Tiredness
PLEASE SEE PRESCRIBING INFORMATION AND MEDICATION GUIDE.
Alkermes® and VIVITROL® are registered trademarks of Alkermes, Inc.
©2013 Alkermes, Inc.
All rights reserved VIV-001317 Printed in U.S.A
w w w.vivitrol.com
Available online (www.vivitrolrems.com/content/pdf/patinfo-counseling-tool.pdf).
Reprinted with permission.53
5-55
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Sample XR-NTX Treatment Agreement
This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care.
Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances
of their individual patients and practice arrangements. The information provided in this form is provided “as is”
with no guarantee as to its accuracy or completeness.
TREATMENT AGREEMENT
I agree to accept the following treatment agreement for extended-release injectable naltrexone (XR-NTX)
offce-based opioid use disorder treatment:
1. The risks and benefts of XR-NTX treatment have been explained to me, and I understand the information provided.
2. The risks and benefts of other treatment for opioid use disorder (including methadone, buprenorphine, and
nonmedication treatments) have been explained to me.
3. I will be on time to my appointments and respectful to the offce staff and other patients.
4. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical
problems.
5. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider.
6. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance
so that my pain will be adequately treated.
7. If I miss a scheduled appointment for my next XR-NTX injection, I understand that I should reschedule the
appointment as soon as possible because it is important to receive the medication on time to reduce the risk of
opioid overdose should I return to use.
8. If I come to the offce intoxicated, I understand that my healthcare provider will not see me.
9. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in
treatment termination from the clinic.
10. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will
count as a positive drug test.
11. I understand that initially I will have weekly offce visits until my condition is stable.
12. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug
tests in a row.
13. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me.
14. I understand that people have died trying to overcome the opioid blockade by taking large amounts of opioids.
15. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to follow
my healthcare provider’s recommendations for additional counseling and/or for help with other problems.
16. I understand that there is no fxed time for being on XR-NTX and that the goal of treatment is for me to stop
using all illicit drugs and become successful in all aspects of my life.
17. I understand that my risk of overdose increases if I go back to using opioids after stopping XR-NTX.
18. I have been educated about the other two FDA-approved medications used to treat opioid use disorder,
methadone and buprenorphine, and I prefer to receive treatment with XR-NTX.
19. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting XR-
NTX treatment and have been informed about methods for preventing pregnancy.
20. I have been informed that if I become pregnant during naltrexone treatment, I should inform my provider and
have a discussion about the risks and benefts of continuing to take XR-NTX.
Other specifc items unique to my treatment include:
Patient Name (print): _____________________________________________________
Patient Signature: ________________________________________________________ Date: ____________________
This form is adapted from ASAM’s Sample Treatment Agreement, which is updated periodically; the most current version of the
agreement is available online (www.asam.org/docs/default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff0
00030b21a.pdf?sfvrsn=0).
Adapted with permission.54
5-56
Medications for Opioid Use Disorder TIP 63
Glossary of TIP Terminology
Abuse liability: The likelihood that a medication
with central nervous system activity will cause
desirable psychological effects, such as euphoria
or mood changes, that promote the medication’s
misuse.
Addiction: As defned by ASAM,55“a primary,
chronic disease of brain reward, motivation,
memory, and related circuitry.” It is characterized
by inability to consistently abstain, impairment
in behavioral control, craving, diminished
recognition of signifcant problems with one’s
behaviors and interpersonal relationships, and
a dysfunctional emotional response. Like other
chronic diseases, addiction often involves cycles
of relapse and remission. The Diagnostic and
Statistical Manual of Mental Disorders, Fifth
Edition56 (DSM-5), does not use the term for
diagnostic purposes, but it commonly describes
the more severe forms of opioid use disorder.
Bioavailability: Proportion of medication
administered that reaches the bloodstream.
Care provider: Encompasses both healthcare
professionals and other professionals who do
not provide medical services, such as counselors
or providers of supportive services. Often
shortened to “provider.”
Cross-tolerance: Potential for people tolerant
to one opioid (e.g., heroin) to be tolerant to
another (e.g., methadone).
Dissociation: Rate at which a drug uncouples
from the receptor. A drug with a longer dissoci-
ation rate will have a longer duration of action
than a drug with a shorter dissociation rate.
Half-life: Rate of removal of a drug from the
body. One half-life removes 50 percent from
the plasma. After a drug is stopped, it takes
fve half-lives to remove about 95 percent from
the plasma. If a drug is continued at the same
dose, its plasma level will continue to rise until it
reaches steady state concentrations after about
fve half-lives.
Healthcare professionals: Physicians, nurse
practitioners, physician assistants, and other
medical service professionals who are eligible
to prescribe medications for and treat patients
with OUD (i.e., until October 1, 2023, clinical
nurse specialists, certifed registered nurse
anesthetists, certifed nurse midwives). The term
“prescribers” also refers to these healthcare
professionals.
Induction: Process of initial dosing with medica-
tion for OUD treatment until the patient reaches
a state of stability; also called initiation.
Intrinsic activity: The degree of receptor
activation attributable to drug binding. Full
agonist, partial agonist, and antagonist are
terms that describe the intrinsic activity of a
drug.
Maintenance treatment: Providing medications
to achieve and sustain clinical remission of
signs and symptoms of OUD and support the
individual process of recovery without a specifc
endpoint (as with the typical standard of care
in medical and psychiatric treatment of other
chronic illnesses).
Medically supervised withdrawal (formerly
called detoxifcation): Using an opioid agonist (or
an alpha-2 adrenergic agonist if opioid agonist is
not available) in tapering doses or other med-
ications to help a patient discontinue illicit or
prescription opioids.
Medical management: Process whereby health-
care professionals provide medication, basic
brief supportive counseling, monitoring of drug
use and medication adherence, and referrals,
when necessary, to addiction counseling and
other services to address the patient’s medical,
mental health, comorbid addiction, and psycho-
social needs.
5-57
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Mutual-help groups: Groups of people who
work together on obtaining and maintaining
recovery. Unlike peer support (e.g., the use of
recovery coaches), mutual-help groups consist
entirely of people who volunteer their time and
typically have no offcial connection to treatment
programs. Most are self-supporting. Although
12-Step groups such as AA and NA are the most
widespread and well-researched type of mutual-
help groups, other groups may be available in
some areas. They range from groups affliated
with a religion or church (e.g., Celebrate
Recovery, Millati Islami) to purely secular groups
(e.g., SMART Recovery, Women for Sobriety).
Offce-based opioid treatment (OBOT):
Providing medication for OUD in settings other
than certifed OTPs.
Opiates: A subclass of opioids derived from
opium (e.g., morphine, codeine, thebaine).
Opioid misuse: The use of prescription opioids
in any way other than as directed by a prescriber;
the use of any opioid in a manner, situation,
amount, or frequency that can cause harm to self
or others.57
Opioid receptor agonist: A substance that
has an affnity for and stimulates physiological
activity at cell receptors in the central nervous
system that are normally stimulated by opioids.
Mu-opioid receptor full agonists (e.g.,
methadone) bind to the mu-opioid receptor and
produce actions similar to those produced by the
endogenous opioid beta-endorphin. Increasing
the dose increases the effect. Mu-opioid
receptor partial agonists (e.g., buprenorphine)
bind to the mu-opioid receptor. Unlike with full
agonists, increasing their dose may not produce
additional effects once they have reached their
maximal effect. At low doses, partial agonists
may produce effects similar to those of full
agonists.
Opioid receptor antagonist: A substance that
has an affnity for opioid receptors in the central
nervous system without producing the physi-
ological effects of opioid agonists. Mu-opioid
receptor antagonists (e.g., naltrexone) can block
the effects of exogenously administered opioids.
Opioid receptor blockade: Blunting or blocking
of the euphoric effects of an opioid through
opioid receptor occupancy by an opioid agonist
(e.g., methadone, buprenorphine) or antagonist
(e.g., naltrexone).
Opioids: All natural, synthetic, and semisynthetic
substances that have effects similar to morphine.
They can be used as medications having such
effects (e.g., methadone, buprenorphine,
oxycodone).
Opioid treatment program (OTP): An
accredited treatment program with SAMHSA
certifcation and DEA registration to administer
and dispense opioid agonist medications that
are approved by FDA to treat opioid addiction.
Currently, these include methadone and
buprenorphine products. Other pharmacother-
apies, such as naltrexone, may be provided but
are not subject to these regulations. OTPs must
provide adequate medical, counseling, voca-
tional, educational, and other assessment and
treatment services either onsite or by referral
to an outside agency or practitioner through a
formal agreement.58
Opioid use disorder (OUD): Per DSM-5,59
a disorder characterized by loss of control
of opioid use, risky opioid use, impaired
social functioning, tolerance, and withdrawal.
Tolerance and withdrawal do not count toward
the diagnosis in people experiencing these
symptoms when using opioids under appropriate
medical supervision. OUD covers a range of
severity and replaces what the DSM-IV termed
“opioid abuse” and “opioid dependence.” An
OUD diagnosis is applicable to a person who
uses opioids and experiences at least 2 of the
11 symptoms in a 12-month period. (See Exhibit
2.11 in Part 2 for full DSM-5 diagnostic criteria
for OUD.)
5-58
Medications for Opioid Use Disorder TIP 63
Peer support: The use of peer support spe-
cialists in recovery to provide nonclinical (i.e.,
not requiring training in diagnosis or treatment)
recovery support services to individuals in
recovery from addiction and to their families.
Peer support specialist: Someone in recovery
who has lived experience in addiction plus skills
learned in formal training. Peer support spe-
cialists may be paid professionals or volunteers.
They are distinguished from members of mutual-
help groups because they maintain contact
with treatment staff. They offer experiential
knowledge that treatment staff often lack.
Prescribers: Healthcare professionals who are
eligible to prescribe medications for OUD.
Psychosocial support: Ancillary services to
enhance a patient’s overall functioning and
well-being, including recovery support services,
case management, housing, employment, and
educational services.
Psychosocial treatment: Interventions that
seek to enhance a patient’s social and mental
functioning, including addiction counseling,
contingency management, and mental health
services.
Receptor affnity: Strength of the bond
between a medication and its receptor. A
medication with high mu-opioid receptor affnity
requires lower concentrations to occupy the
same number of mu-opioid receptors as a drug
with lower mu-opioid receptor affnity. Drugs
with high mu-opioid receptor affnity may
displace drugs with lower affnity.
Recovery: A process of change through which
individuals improve their health and wellness,
live a self-directed life, and strive to reach their
full potential. Even individuals with severe and
chronic SUDs can, with help, overcome their
SUDs and regain health and social function.
Although abstinence from all substance misuse
is a cardinal feature of a recovery lifestyle, it is
not the only healthy, prosocial feature. Patients
taking FDA-approved medication to treat OUD
can be considered in recovery.
Recovery capital: The sum of the internal (e.g.,
motivation, self-effcacy, spirituality) and external
(e.g., access to health care, employment, family
support) resources that an individual can draw on
to begin and sustain recovery from SUDs.
Recovery-oriented care: A service orientation
that supports individuals with behavioral health
conditions in a process of change through which
they can improve their health and wellness, live
self-directed lives, and strive to reach their full
potential.
Relapse: A process in which a person with OUD
who has been in remission experiences a return
of symptoms or loss of remission. A relapse is
different from a return to opioid use in that
it involves more than a single incident of use.
Relapses occur over a period of time and can be
interrupted. Relapse need not be long lasting.
The TIP uses relapse to describe relapse preven-
tion, a common treatment modality.
Remission: A medical term meaning a
disappearance of signs and symptoms of the
disease.60 DSM-5 defnes remission as present in
people who previously met OUD criteria but no
longer meet any OUD criteria (with the possible
exception of craving).61 Remission is an essential
element of recovery.
Return to opioid use: One or more instances
of opioid misuse without a return of symptoms
of OUD. A return to opioid use may lead to
relapse.
Tolerance: Alteration of the body’s responsive-
ness to alcohol or other drugs (including opioids)
such that higher doses are required to produce
the same effect achieved during initial use. See
also medically supervised withdrawal.
5-59
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
Notes
1 Centers for Disease Control and Prevention, National
Center for Health Statistics. (2020). Multiple Cause of
Death 2018-2019 on CDC WONDER Online Database,
released in 2020. Retrieved April 29, 2021, from https://
wonder.cdc.gov/mcd.html
2 National Highway Traffc Safety Administration. (2020).
NHTSA Releases 2019 Crash Fatality Data. Retrieved
April 29, 2021, from www.nhtsa.gov/press-releases/
nhtsa-releases-2019-crash-fatality-data
3 Babor, T. F., Higgins-Biddle, J. C., Saunders, J. B., &
Monteiro, M. G. (2001). The Alcohol Use Disorders
Identifcation Test. Guidelines for use in primary care
(2nd ed.). Geneva, Switzerland: The World Health
Organization.
4 Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D., &
Bradley, K. A. (1998). The AUDIT alcohol consumption
questions (AUDIT-C): An effective brief screening test for
problem drinking. Ambulatory Care Quality Improvement
Project (ACQUIP). Alcohol Use Disorders Identifcation
Test. Archives of Internal Medicine, 158(16), 1789–1795.
5 Skinner, H. A. (1982). The Drug Abuse Screening Test.
Addictive Behavior, 7(4), 363–371.
6 Yudko, E., Lozhkina, O., & Fouts, A. (2007). A
comprehensive review of the psychometric properties
of the Drug Abuse Screening Test. Journal of Substance
Abuse Treatment, 32, 189–198.
7 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed., p. 541).
Arlington, VA: American Psychiatric Publishing.
8 Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., Rickert,
W., & Robinson, J. (1989). Measuring the heaviness of
smoking: Using self-reported time to the frst cigarette of
the day and number of cigarettes smoked per day. British
Journal of Addiction, 84(7), 791–799.
9 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D.,
& Saitz, R. (2009). Primary care validation of a single-
question alcohol screening test. Journal of General
Internal Medicine, 24(7), 783–788. doi:10.1007/
s11606-009-0928-6
10 Substance Abuse and Mental Health Services
Administration. (2016). SAMHSA opioid overdose
prevention toolkit. HHS Publication No. (SMA) 16-4742.
Rockville, MD: Substance Abuse and Mental Health
Services Administration.
11 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D.,
& Saitz, R. (2010). A single-question screening test for
drug use in primary care. Archives of Internal Medicine,
170(13), 1155–1160.
12 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A
primary care approach to substance misuse. American
Family Physician, 88(2), 113–121.
13 McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G.,
Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016).
Performance of the Tobacco, Alcohol, Prescription
Medication, and Other Substance Use (TAPS) Tool for
substance use screening in primary care patients. Annals
of Internal Medicine, 165(10), 690–699.
14 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M.,
Osterberg, L., & Smith, B. (2015). Screen of drug use:
Diagnostic accuracy of a new brief tool for primary care.
JAMA Internal Medicine, 175(8), 1371–1377.
15 Lynch, K. (2014). San Francisco General Hospital
laboratory protocol. San Francisco, CA: San Francisco
General Hospital.
16 Warner, E., & Lorch, E. (2014). Laboratory diagnosis.
In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.),
Principles of addiction medicine (5th ed., pp. 332–343).
Philadelphia, PA: Wolters Kluwer.
17 Milone, M. C. (2012). Laboratory testing for prescription
opioids. Journal of Medical Toxicology,8(4), 408–416.
doi:10.1007/s13181-012-0274-7
18 Leavitt, S. B., Shinderman, M., Maxwell, S., Eap, C. B.,
& Paris, P. (2000). When “enough” is not enough: New
perspectives on optimal methadone maintenance dose.
Mount Sinai Journal of Medicine, 67(5–6), 404–411.
19 American Society of Addiction Medicine. (2016). Sample
offce-based opioid use disorder policy and procedure
manual. Retrieved October 19, 2017, from www.asam.
org/docs/default-source/advocacy/sample
-diversion-policy.pdf?sfvrsn=0
20 Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed.nlm
.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
21 Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed.nlm
.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
22 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
23 Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
5-60
Medications for Opioid Use Disorder TIP 63
24 Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
25 Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
26 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
27 Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed.nlm
.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
28 Indivior. (2015). Suboxone (buprenorphine and naloxone)
sublingual flm: Full prescribing information. Retrieved
October 16, 2017, from www.suboxone.com/pdfs/
prescribing-information.pdf
29 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
30 Durand, F., & Valla, D. (2008). Assessment of prognosis of
cirrhosis. Seminars in Liver Disease, 28(1), 110–122.
31 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetics, 54(8), 837–849.
32 Roxane Laboratories. (2015). Buprenorphine HCl
sublingual tablets: Full prescribing information. Retrieved
October 16, 2017, from http://dailymed.nlm
.nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a
-b769-465c-a2f8-099868dfcd2f
33 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J.
(2015). Pharmacokinetics of sublingual buprenorphine
and naloxone in subjects with mild to severe hepatic
impairment (Child-Pugh classes A, B, and C), in hepatitis
C virus-seropositive subjects, and in healthy volunteers.
Clinical Pharmacokinetic, 54(8), 837–849.
34 Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
35 Donovan, D. M., Ingalsbe, M. H., Benbow, J., & Daley,
D. C. (2013). 12-step interventions and mutual support
programs for substance use disorders: An overview.
Social Work in Public Health, 28(3–4), 313–332.
36 McLellan, A. T., & White, W. (2012). Opioid maintenance
and recovery-oriented systems of care: It is time to
integrate (p. 2). London, England: National Treatment
Agency for Substance Misuse.
37 Substance Abuse and Mental Health Services
Administration. (2016). Pocket guide: Medication-assisted
treatment of opioid use disorder. HHS Publication No.
(SMA) 16-4892PG. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
38 Substance Abuse and Mental Health Services
Administration. (2015). Clinical use of extended-release
injectable naltrexone in the treatment of opioid use
disorder: A brief guide. HHS Publication No. (SMA)
14-4892R. Rockville, MD: Substance Abuse and Mental
Health Services Administration.
39 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M.
(2014). Buprenorphine maintenance versus placebo
or methadone maintenance for opioid dependence.
Cochrane Database of Systematic Reviews, 2014(2), 1–84.
40 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009).
Methadone maintenance therapy versus no opioid
replacement therapy for opioid dependence. Cochrane
Database of Systematic Reviews, 2009(3), 1–19.
41 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database
Systems Review, 4, CD001333.
42 Krupitsky, E., Zvartau, E., Blokhina, E., Verbitskaya, E.,
Wahlgren, V., Tsoy-Podosenin, M., … Woody, G. E.
(2012.) Randomized trial of long-acting sustained-release
naltrexone implant vs oral naltrexone or placebo for
preventing relapse to opioid dependence. Archives of
General Psychiatry, 69(9), 973–981.
43 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V.,
Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016).
Extended-release naltrexone to prevent opioid relapse
in criminal justice offenders. New England Journal of
Medicine, 374(13), 1232–1242.
44 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer,
U., & Verster, A. (2011). Oral naltrexone maintenance
treatment for opioid dependence. Cochrane Database of
Systematic Reviews, 2, CD001333.
45 Substance Abuse and Mental Health Services
Administration. (2016). Sublingual and transmucosal
buprenorphine for opioid use disorder: Review
and update. Advisory, Vol. 15, Issue 1. Rockville,
MD: Substance Abuse and Mental Health Services
Administration.
5-61
TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder
46 Lintzeris, N., & Nielsen, S. (2010). Benzodiazepines,
methadone and buprenorphine: Interactions and
clinical management. American Journal on Addictions,
19(1), 59–72.
47 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA)
PEP15-FEDGUIDEOTP. Rockville, MD: Substance Abuse
and Mental Health Services Administration.
48 Lofwall, M. & Walsh, S. (2014). A review of
buprenorphine diversion and misuse: The current
evidence base and experiences from around the world
(p. 316). Journal of Addiction Medicine, 8(5), 315–326.
49 American Society of Addiction Medicine. (2016).
Sample offce-based opioid use disorder policy and
procedure manual. Retrieved October 19, 2017, from
www.asam.org/docs/default-source/advocacy/sample
-diversion-policy.pdf?sfvrsn=0
50 Food and Drug Administration (2017, May).
Appropriate use checklist: Buprenorphine-containing
transmucosal products for opioid dependence. Silver
Spring, MD: Food and Drug Administration.
51 American Society of Addiction Medicine. (2017).
Sample treatment agreement. Retrieved October
19, 2017, from www.asam.org/docs/default-source
/advocacy/sample-treatment-agreement30fa159472bc
604ca5b7ff000030b21a.pdf?sfvrsn=0
52 Alkermes. (2015). Key techniques to reduce severe
injection site reactions: VIVITROL (naltrexone for
extended release injectable suspension) intramuscular
injection. Retrieved January 9, 2018, from www
.vivitrolrems.com/content/pdf/patinfo-injection
-poster.pdf
53 Alkermes. (2013). Patient counseling tool: VIVITROL
(naltrexone for extended-release injectable suspension).
Retrieved January 9, 2018, from www.vivitrolrems.com
/content/pdf/patinfo-counseling-tool.pdf
54 American Society of Addiction Medicine. (2017). Sample
treatment agreement. Retrieved October 19, 2017, from
www.asam.org/docs/default-source
/advocacy/sample-treatment-agreement30fa159472bc60
4ca5b7ff000030b21a.pdf?sfvrsn=0
55 American Society of Addiction Medicine. (2011).
Defnition of addiction. Retrieved October 30, 2017, from
www.asam.org/resources/defnition-of-addiction
56 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
57 Department of Health and Human Services, Offce of the
Surgeon General. (2016). Facing addiction in America:
The Surgeon General’s report on alcohol, drugs, and
health. Washington, DC: Department of Health and
Human Services.
58 Substance Abuse and Mental Health Services
Administration. (2015). Federal guidelines for opioid
treatment programs. HHS Publication No. (SMA) PEP15-
FEDGUIDEOTP. Rockville, MD: Substance Abuse and
Mental Health Services Administration.
59 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
60 National Cancer Institute. (n.d.). NCI dictionary of cancer
terms: Remission. Retrieved November 22, 2017, from
www.cancer.gov/publications/dictionaries
/cancer-terms?cdrid=45867
61 American Psychiatric Association. (2013). Diagnostic and
statistical manual of mental disorders (5th ed.). Arlington,
VA: American Psychiatric Publishing.
This page intentionally left blank.
Available TIPs
TIPs may be ordered or downloaded for free from SAMHSA’s Publications Ordering webpage at https://
store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español).
TIP 24 A Guide to Substance Abuse Services for TIP 46 Substance Abuse: Administrative Issues in
Primary Care Clinicians Outpatient Treatment
TIP 25 Substance Abuse Treatment and Domestic TIP 47 Substance Abuse: Clinical Issues in Intensive
Violence Outpatient Treatment
TIP 26 Treating Substance Use Disorder in Older TIP 48 Managing Depressive Symptoms in
Adults Substance Abuse Clients During Early
TIP 27 Comprehensive Case Management for
Recovery
Substance Abuse Treatment TIP 49 Incorporating Alcohol Pharmacotherapies
TIP 29 Substance Use Disorder Treatment for
Into Medical Practice
People With Physical and Cognitive TIP 50 Addressing Suicidal Thoughts and Behaviors
Disabilities in Substance Abuse Treatment
TIP 30 Continuity of Offender Treatment for TIP 51 Substance Abuse Treatment: Addressing the
Substance Use Disorders From Institution to Specifc Needs of Women
Community TIP 52 Clinical Supervision and Professional
TIP 31 Screening and Assessing Adolescents for Development of the Substance Abuse
Substance Use Disorders Counselor
TIP 34 Brief Interventions and Brief Therapies for TIP 53 Addressing Viral Hepatitis in People With
Substance Abuse Substance Use Disorders
TIP 35 Enhancing Motivation for Change in TIP 54 Managing Chronic Pain in Adults With or in
Substance Abuse Treatment Recovery From Substance Use Disorders
TIP 36 Substance Abuse Treatment for Persons with TIP 55 Behavioral Health Services for People Who
Child Abuse and Neglect Issues Are Homeless
TIP 37 Substance Abuse Treatment for Persons TIP 56 Addressing the Specifc Behavioral Health
With HIV/AIDS Needs of Men
TIP 38 Integrating Substance Abuse Treatment and TIP 57 Trauma-Informed Care in Behavioral Health
Vocational Services Services
TIP 39 Substance Use Disorder Treatment and TIP 58 Addressing Fetal Alcohol Spectrum
Family Therapy Disorders (FASD)
TIP 41 Substance Abuse Treatment: Group Therapy TIP 59 Improving Cultural Competence
TIP 42 Substance Abuse Treatment for Persons TIP 60 Using Technology-Based Therapeutic Tools
With Co-Occurring Disorders in Behavioral Health Services
TIP 44 Substance Abuse Treatment for Adults in TIP 61 Behavioral Health Services for American
the Criminal Justice System Indians and Alaska Natives
TIP 45 Detoxifcation and Substance Abuse TIP 63 Medications for Opioid Use Disorder
Treatment
Publication No. PEP21-02-01-002
First released 2018. Revised 2019, 2020, and 2021.
U.S. Department of Health and Human Services
Substance Abuse and Mental Health Services Administration
Center for Substance Abuse Treatment
TIP 63_Comp FrontMatter
TIP 63_ExecutiveSummary
TIP 63_Part1
TIP 63_Part2
TIP 63_Part3
TIP 63_Part4
TIP 63_Part5