Phenelzine has some of the strictest interaction rules in psychiatry. Many combinations are flat-out contraindicated because they can trigger hypertensive crisis, serotonin toxicity-like reactions, severe blood pressure instability, or dangerous CNS effects.
With: SSRIs / SNRIs
Risk: High risk of severe reaction due to pharmacodynamic interaction. Washouts are mandatory.
Action: Do not combine. Wait at least 2 weeks after stopping most SSRIs/SNRIs before starting phenelzine. For fluoxetine, wait 5 weeks. After stopping phenelzine, wait 14 days before starting an SSRI/SNRI.
With: Tricyclic antidepressants and related agents (multiple agents in this class are contraindicated in the notes)
Risk: High-risk interaction. Can cause severe adverse reactions.
Action: Avoid combination. Use strict washout timing when switching.
With: Bupropion
Risk: Contraindicated combination; high-risk interaction.
Action: Avoid combination. Wait at least 14 days between stopping phenelzine and starting bupropion (and vice versa).
With: Buspirone
Risk: Contraindicated combination; high-risk interaction.
Action: Avoid combination. Wait at least 14 days between stopping phenelzine and starting buspirone (Canadian labeling notes 10 days).
With: Meperidine
Risk: Dangerous interaction; can be severe and life-threatening.
Action: Contraindicated. Make sure all clinicians (including ER and anesthesia) know you take an MAOI.
With: Dextromethorphan (common in cough/cold meds)
Risk: Contraindicated interaction risk.
Action: Avoid. Check OTC cough/cold labels carefully.
With: Sympathomimetics and stimulants (including amphetamines, methylphenidate, dopamine, norepinephrine; and related compounds)
Risk: Can dangerously raise blood pressure and trigger hypertensive crisis.
Action: Avoid. This includes many decongestants and stimulant-type products.
With: Alcohol and other CNS depressants
Risk: Can worsen CNS depression, coordination impairment, and judgment problems.
Action: Avoid or use extreme caution based on individualized guidance. If you drink at all, discuss explicitly with your prescriber.
With: Tyramine-rich foods and certain dietary triggers (and poor food storage/freshness)
Risk: Hypertensive crisis risk.
Action: Avoid aged/fermented/pickled/smoked/spoiled protein foods; aged cheeses; certain cured meats; yeast extracts; some alcoholic beverages (beer, wine); and avoid spoiled/improperly stored protein foods. Continue diet restrictions for 2 weeks after stopping.
With: Surgery and anesthesia (general or spinal); local anesthetics with sympathomimetic vasoconstrictors
Risk: Blood pressure instability and exaggerated hypotension or hypertensive reactions.
Action: Manufacturer guidance: discontinue phenelzine at least 10 days prior to elective surgery. Any perioperative plan should be coordinated with psychiatry and anesthesia, avoiding meperidine and indirect-acting adrenergic agents.