Tranylcypromine Drug Interactions: What to Avoid and What to Tell Your Doctor

Tranylcypromine has one of the most extensive drug interaction profiles of any medication in common use. Because it irreversibly inhibits monoamine oxidase, its interaction risks don't simply end when you take each dose — they persist for up to 10 days after your last dose. Every doctor, dentist, pharmacist, or urgent care provider you see must know you are taking tranylcypromine.

This guide covers the most critical interactions to be aware of — organized by category and severity.

Category 1: Absolutely Contraindicated — Never Combine With Tranylcypromine

These medications are contraindicated with tranylcypromine and should not be taken during or for at least 14 days after stopping tranylcypromine (or at least 10 days before starting tranylcypromine after stopping them):

SSRIs — Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), escitalopram (Lexapro), citalopram (Celexa). Risk: potentially fatal serotonin syndrome. Wait at least 5 weeks after stopping fluoxetine (due to its long half-life) before starting tranylcypromine.

SNRIs — Venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine, milnacipran, levomilnacipran. Risk: serotonin syndrome.

TCAs (Tricyclic antidepressants) — Amitriptyline, nortriptyline, clomipramine, imipramine. Risk: serotonin syndrome and hypertensive reactions.

Other MAOIs — Phenelzine (Nardil), isocarboxazid (Marplan), selegiline. Combining MAOIs is contraindicated; wait at least 1 week between MAOI agents.

Meperidine (Demerol) — Opioid analgesic; risk of severe, potentially fatal serotonin reaction. Inform all healthcare providers and ER staff that you take tranylcypromine.

Dextromethorphan (DXM) — Found in cough medicines (Robitussin DM, NyQuil, and many OTC cold products). Risk: serotonin syndrome. Check all OTC cold medications before use.

Bupropion (Wellbutrin, Zyban) — Dopamine/norepinephrine reuptake inhibitor; risk of hypertensive crisis and seizures. Wait at least 14 days after stopping tranylcypromine before starting bupropion.

Sympathomimetics — Amphetamines (Adderall, Vyvanse), methylphenidate (Ritalin, Concerta), pseudoephedrine, phenylephrine (nasal decongestants). Risk: acute hypertensive crisis.

Buspirone — Anti-anxiety medication; risk of increased serotonin levels and hypertension when combined with tranylcypromine.

Category 2: Important Interactions Requiring Caution or Provider Discussion

Tramadol — Opioid with serotonergic activity; risk of serotonin syndrome. Often overlooked because it's considered a 'mild' pain reliever.

St. John's Wort — Herbal supplement with serotonergic activity; risk of serotonin syndrome. Many patients don't think of supplements as 'real medications' — always disclose this.

Cyclobenzaprine (Flexeril) — Muscle relaxant with TCA-like structure; risk of serotonin syndrome; contraindicated within 14 days of an MAOI.

Linezolid and IV methylene blue — Antibiotic (linezolid) and diagnostic agent (methylene blue) that also inhibit MAO; risk of serotonin syndrome if combined with tranylcypromine.

Carbamazepine (Tegretol) — Anticonvulsant and mood stabilizer; may interact with tranylcypromine; discuss with your prescriber.

General anesthesia — Tranylcypromine should be discontinued at least 10 days prior to elective surgery. Alert your anesthesiologist and surgeon that you are or recently were on tranylcypromine.

OTC Medications That Are Not Safe with Tranylcypromine

Many over-the-counter medications are contraindicated. Always check the label and ask a pharmacist before taking any new OTC product. Avoid:

Any cough or cold medicine containing dextromethorphan (DXM) — look for 'DM' in the product name

Decongestants containing pseudoephedrine (Sudafed) or phenylephrine

Weight loss supplements containing stimulants or ephedra/ma huang

St. John's Wort supplements

The Washout Period: When Do Interaction Risks End?

MAO inhibition from tranylcypromine persists for up to 10 days after the last dose. This means:

Wait at least 14 days after stopping tranylcypromine before starting any SSRI, SNRI, or TCA

Wait at least 1 week after stopping tranylcypromine before starting another MAOI

Continue tyramine dietary restrictions for at least 2 weeks after stopping tranylcypromine

For more on side effects and warning signs, see: Tranylcypromine Side Effects: What to Expect and When to Call Your Doctor.

For a general overview of the medication, see: What Is Tranylcypromine? Uses, Dosage, and What You Need to Know in 2026.