What painkiller should be avoided in a patient taking Monoamine Oxidase Inhibitor (MAOI) for depression?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 30, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Patients on monoamine oxidase inhibitors (MAOIs) for depression should avoid opioid painkillers, particularly meperidine, tramadol, methadone, levorphanol, fentanyl, and tapentadol, for postoperative pain management due to the increased risk of serotonin syndrome. This is because these medications can interact with MAOIs and cause serotonin syndrome, a potentially fatal condition characterized by neuroexcitatory symptoms, excitatory autonomic dysfunction, and excitatory neuromuscular abnormalities 1. The use of one of these serotonergic opioids with one or more medications that affect serotonin levels, such as MAOIs, increases the perioperative risk of serotonin syndrome.

Some key points to consider when managing postoperative pain in patients on MAOIs include:

  • Avoiding the use of opioids with serotonin reuptake inhibitory activity, such as meperidine, tramadol, and methadone, due to the increased risk of serotonin syndrome 1
  • Avoiding the use of sympathomimetic drugs like ephedrine and pseudoephedrine found in some pain formulations
  • Considering safer alternatives for postoperative pain, such as acetaminophen, certain NSAIDs (with caution regarding bleeding risk), and carefully monitored use of morphine, hydromorphone, or fentanyl under close medical supervision
  • Informing the anesthesiologist and surgeon about the patient's MAOI therapy before surgery to plan appropriate pain management

The risk of serotonin syndrome is a significant concern when using MAOIs and certain opioids together, and heightened vigilance is recommended postoperatively to avoid coadministration of CYP2D6 inhibitors and ensure effective analgesia 1. By taking these precautions, healthcare providers can minimize the risk of adverse interactions and ensure safe and effective pain management for patients on MAOIs.

From the FDA Drug Label

Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact:MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5. 7)]. Intervention:Do not use morphine sulfate tablets in patients taking MAOIs or within 14 days of stopping such treatment.

The medication to be avoided in a patient on MAOI for depression is morphine sulfate tablets due to the risk of serotonin syndrome or opioid toxicity. 2

From the Research

Medication to Avoid with MAOI

When a patient is on Monoamine Oxidase Inhibitors (MAOI) for depression, certain medications should be avoided due to potential adverse interactions.

  • The following types of medications can elevate blood pressure via sympathomimetic actions and should be avoided:
    • Phenylephrine
    • Oxymetazoline 3
  • Medications that can increase serotonin levels via 5-HT reuptake inhibition should also be avoided, including:
    • Dextromethorphan
    • Chlorpheniramine
    • Brompheniramine 3
  • Certain opioid analgesics can precipitate life-threatening serotonin toxicity when combined with MAOIs, including:
    • Pethidine (meperidine)
    • Tramadol
    • Methadone
    • Dextromethorphan
    • Propoxyphene 4
  • Illicit drugs that stimulate the central nervous system, such as ecstasy (MDMA, 3,4-methylenedioxymethamphetamine), can act as serotonin releasers and should be avoided 3

Safe Alternatives for Pain Management

For patients on MAOI, the following opioid analgesics are known not to be serotonin reuptake inhibitors and do not precipitate serotonin toxicity with MAOIs:

  • Morphine
  • Codeine
  • Oxycodone
  • Buprenorphine 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.