MAOIs — Tyramine Crisis & Interactions

A patient on phenelzine eats aged cheddar at a party and arrives in the ED with a blood pressure of 240/130. The cheese didn't cause the crisis — the missing enzyme did.

Monoamine oxidase inhibitors (MAOIs) like phenelzine, tranylcypromine, and isocarboxazid irreversibly block monoamine oxidase, the enzyme that breaks down norepinephrine, serotonin, and dopamine. This increases neurotransmitter availability and treats depression — but it also disables the gut's ability to degrade tyramine, a monoamine derived from the amino acid tyrosine found in aged and fermented foods. Normally, MAO in the intestinal wall neutralizes dietary tyramine before it reaches the bloodstream. Without that safeguard, tyramine floods the system, triggering massive norepinephrine release from sympathetic nerve terminals. The result is hypertensive crisis: severe occipital headache, stiff neck, diaphoresis, nausea, and blood pressure that can spike above 180/120 mmHg, risking stroke or intracranial hemorrhage. Treatment is IV phentolamine (an alpha-adrenergic blocker). The dietary restriction must continue for 14 days after discontinuing the MAOI because enzyme inhibition is irreversible — the body needs time to synthesize new MAO.

Key Distinctions

Don't confuse hypertensive crisis (tyramine + MAOI → norepinephrine surge → dangerously high BP) with serotonin syndrome (MAOI + serotonergic drug → hyperthermia, clonus, agitation). Both are MAOI emergencies but have different triggers and presentations. Students forget the 14-day washout: stopping the drug does not immediately restore MAO activity. Restricted foods include aged cheeses, cured meats, sauerkraut, soy sauce, draft beer, and red wine — not all protein foods.

Clinical Pearl

Think "aged, cured, or fermented — if bacteria worked on it, it's loaded with tyramine." No aged cheese, no cured meat, no tap beer, no soy sauce — for 14 days after the last dose.