Related | Perioperative Medication Management Appendix (Methylene Blue and Serotonin Syndrome)
Appendix C: Methylene Blue and Serotonin Syndrome
From: Perioperative Medication Management – Adult/Pediatric – Inpatient/Ambulatory
Clinical Practice Guideline
Last Reviewed 2/2020; Last Updated 6/2019
Contact information: Philip J. Trapskin, PharmD, Phone Number: (608) 263-1328, PTrapskin@uwhealth.org
Summary:
Although the exact mechanism of this drug interaction is unknown, methylene blue inhibits the action of
monoamine oxidase A - an enzyme responsible for breaking down serotonin in the brain. It is believed that when
methylene blue is given to patients taking serotonergic psychiatric medications, high levels of serotonin can build up
in the brain, causing toxicity. See Table 1. Psychiatric medications with serotonergic activity.
• In emergency situations requiring life-threatening or urgent treatment with methylene blue (as described
above), the availability of alternative interventions should be considered and the benefit of methylene blue
treatment should be weighed against the risk of serotonin toxicity. If methylene blue must be administered to a
patient receiving a serotonergic drug, the serotonergic drug must be immediately stopped, and the patient should
be closely monitored for emergent symptoms of CNS toxicity for two weeks (five weeks if fluoxetine [Prozac] was
taken), or until 24 hours after the last dose of methylene blue, whichever comes first.
• In non-emergency situations when non-urgent treatment with methylene blue is contemplated and planned,
the serotonergic psychiatric medication should be stopped to allow its activity in the brain to dissipate. Most
serotonergic psychiatric drugs should be stopped at least 2 weeks in advance of methylene blue treatment.
Fluoxetine (Prozac), which has a longer half-life compared to similar drugs, should be stopped at least 5 weeks
in advance
• Possible signs/symptoms of Serotonin Syndrome: mental status changes, muscle twitching, excessive sweating,
shivering or shaking, diarrhea, ataxia, fever
• Treatment with the serotonergic psychiatric medication may be resumed 24 hours after the last dose of
methylene blue
• Serotonergic psychiatric medications should not be started in a patient receiving methylene blue. Wait until 24
hours after the last dose of methylene blue before starting the antidepressant.
References:
1. FDA Drug Safety Communication. http://www.fda.gov/Drugs/DrugSafety/ucm263190.htm#Hcp. Updated
10/20/2011.
2. Bach KK, Lindsay FW, Berg LS, Howard RS. Prolonged postoperative disorientation after methylene blue
infusion during parathyroidectomy. Anesth Analg. 2004;99:1573-4.
3. Kartha SS, Chacko CE, Bumpous JM, Fleming M, Lentsch EJ, Flynn MB. Toxic metabolic encephalopathy
after parathyroidectomy with methylene blue localization. Otolaryngol Head Neck Surg. 2006;135:765-8.
Effective 4/6/2020. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2020 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 04/2020CCKM@uwhealth.org
Table 1. Psychiatric medications with serotonergic activity
Generic name Found in Brand name(s)
Selective Serotonin Reuptake Inhibitors (SSRIs)
paroxetine Paxil, Paxil CR, Pexeva
fluvoxamine Luvox, Luvox CR
fluoxetine Prozac, Sarafem, Symbyax
sertraline Zoloft
citalopram Celexa
escitalopram Lexapro
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
venlafaxine Effexor, Effexor XR
desvenlafaxine Pristiq
duloxetine Cymbalta
Tricyclic Antidepressants (TCAs)
amitriptyline Amitid, Amitril, Elavil, Endep, Etrafon, Limbitrol, Triavil
desipramine Norpramin, Pertofrane
clomipramine Anafranil
imipramine Tofranil, Tofranil PM, Janimine, Pramine, Presamine
nortriptyline Pamelor, Aventyl hydrochloride
protriptyline Vivactil
doxepin Sinequan, Zonalon, Silenor
trimipramine Surmontil
Monoamine Oxidase Inhibitors (MAOIs)
isocarboxazid Marplan
phenelzine Nardil
selegiline Emsam, Eldepryl, Zelapar
tranylcypromine Parnate
Other Psychiatric Medications
amoxapine Asendin
maprotiline Ludiomil
nefazodone Serzone
trazodone Desyrel, Oleptro, Trialodine
bupropion Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban, Aplenzin
buspirone Buspar
vilazodone Viibryd
mirtazapine Remeron, Remeron Soltab
Effective 4/6/2020. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2020 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission.
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 04/2020CCKM@uwhealth.org
Appendix C: Methylene Blue and Serotonin Syndrome