What medications and substances should be avoided in a patient with a history of substance use disorder taking Monoamine Oxidase Inhibitors (MAOIs)?

Medications and Substances to Avoid with MAOIs

Patients taking MAOIs must avoid sympathomimetic drugs, serotonergic medications, certain opioids, tyramine-containing foods, and specific over-the-counter products due to life-threatening risks of hypertensive crisis and serotonin syndrome. 1, 2

Critical Drug Contraindications

Serotonergic Medications (Risk: Serotonin Syndrome)

• SSRIs and SNRIs are absolutely contraindicated with MAOIs due to risk of life-threatening serotonin syndrome 2, 3
• Tricyclic antidepressants (TCAs) should be avoided; consider alternative agents depending on indication 1
• Other MAOIs cannot be combined; requires 2-week washout period between MAOI medications (5 weeks for fluoxetine) 2
• Triptans (sumatriptan, etc.) are contraindicated within 24 hours of MAOI use due to serotonin syndrome risk 4

Opioid Analgesics (Risk: Serotonin Syndrome & Hypertensive Crisis)

• Meperidine (pethidine) is specifically contraindicated and has caused fatalities when combined with MAOIs 2, 5
• Tramadol, methadone, fentanyl, dextromethorphan, and propoxyphene are weak serotonin reuptake inhibitors and must be avoided 2, 6, 5
• Safe opioid alternatives: Morphine, codeine, oxycodone, and buprenorphine do not precipitate serotonin toxicity with MAOIs 5

Sympathomimetic Agents (Risk: Hypertensive Crisis)

• All decongestants containing pseudoephedrine, phenylephrine, and oxymetazoline are contraindicated due to hypertensive crisis risk 1, 2
• Amphetamines and stimulants (methylphenidate, dexmethylphenidate, dextroamphetamine) can cause severe hypertensive crisis leading to stroke and death 1, 2
• Requires 2-week washout period before starting stimulants after stopping MAOIs, and vice versa 2

Over-the-Counter Medications to Avoid

• Dextromethorphan (cough suppressants) increases serotonin syndrome risk 2, 7
• Cold medications with sympathomimetics can trigger hypertensive crisis 2, 7
• Antihistamines: Chlorpheniramine and brompheniramine have serotonergic activity and should be avoided 7

Substances of Abuse (Critical for Patients with Substance Use History)

Recreational Drugs (Risk: Hypertensive Crisis & Serotonin Syndrome)

• Cocaine and methamphetamine cause dangerous blood pressure elevations with MAOIs 1
• MDMA (ecstasy) acts as a serotonin releaser and has both serotonergic and sympathomimetic activity, creating dual risk 2, 7
• "Bath salts" (MDPV) are contraindicated due to sympathomimetic effects 1
• All illicit stimulants must be discontinued or avoided in patients on MAOIs 1

Alcohol

• Limit alcohol to ≤1 drink daily for women and ≤2 drinks daily for men 1

Dietary Restrictions

Tyramine-Containing Foods (Risk: Hypertensive Crisis)

• Avoid tyramine-containing foods including aged cheeses, aged/cured meats, fermented foods, and certain alcoholic beverages 1
• As little as 8-10 mg of tyramine can cause life-threatening blood pressure elevations when MAO-A is inhibited 7
• Tyramine is a potent norepinephrine releaser that accumulates to toxic levels when MAO-A cannot degrade it 7

Herbal Supplements to Avoid

• St. John's Wort has MAOI properties and creates dangerous interactions 1
• Ma Huang (ephedra) contains sympathomimetic compounds 1
• Yohimbine should be avoided 1
• L-tryptophan supplements increase serotonin syndrome risk 6

Other Medication Interactions

Ergot-Containing Medications

• Ergotamine, dihydroergotamine, and methysergide cannot be used within 24 hours of MAOIs due to prolonged vasospastic reactions 4

Antipsychotics

• Atypical antipsychotics (clozapine, olanzapine) can elevate blood pressure and should be used with extreme caution; consider alternatives like aripiprazole or ziprasidone 1, 2

Other Medications Requiring Caution

• NSAIDs should be avoided when possible; consider acetaminophen or tramadol alternatives (though tramadol itself is contraindicated with MAOIs) 1
• Systemic corticosteroids should be limited; consider inhaled or topical alternatives when feasible 1

Safe Alternatives for Common Symptoms

For Cold/Allergy Symptoms

• Saline nasal sprays or rinses are safe alternatives to decongestants 2
• Intranasal corticosteroids (fluticasone, mometasone) are generally safe 2
• Second-generation antihistamines (loratadine, cetirizine) are safer options than first-generation antihistamines 2

For Pain Management

• Morphine, codeine, oxycodone, and buprenorphine are safe opioid options 5
• Acetaminophen is a safe non-opioid analgesic 1

Clinical Monitoring and Patient Education

Signs of Hypertensive Crisis

• Sudden severe headache (often described as "thunderclap"), severe blood pressure elevation, chest pain, palpitations, stroke, seizures, and hyperthermia 2
• These symptoms require immediate emergency care 2

Signs of Serotonin Syndrome

• Mental status changes, autonomic instability, neuromuscular abnormalities including confusion, agitation, tremor, hyperreflexia, clonus, hyperthermia, tachycardia 3, 6
• Myoclonus (muscle twitching) occurs in 57% of cases and is the most common finding 6
• Symptoms typically emerge within 24-48 hours after combining medications or dose increases 6
• Mortality rate is approximately 11% in severe cases, with complications including rhabdomyolysis, renal failure, seizures 6

Essential Patient Instructions

• Inform all healthcare providers (including dentists, emergency physicians) about MAOI use before receiving any medications 2
• Avoid all over-the-counter medications without consulting prescriber, including cold remedies, allergy medications, pain relievers, and supplements 2, 7
• Read all medication labels for sympathomimetic ingredients or serotonergic compounds 2
• Avoid energy drinks and weight loss products that may contain stimulants 2

Common Pitfalls to Avoid

• Underestimating washout periods: Always maintain 2-week washout when switching between MAOIs and other serotonergic medications (5 weeks for fluoxetine) 2
• Overlooking hidden sympathomimetics: Many over-the-counter products contain pseudoephedrine or phenylephrine without prominent labeling 7, 8
• Assuming all opioids are safe: Only morphine, codeine, oxycodone, and buprenorphine are confirmed safe; avoid the phenylpiperidine series 5
• Failing to screen for substance use: Patients with substance use history require explicit counseling about dangers of cocaine, methamphetamine, and MDMA with MAOIs 2