Prescription ·Strong evidence ·Reviewed May 2026
Tranylcypromine is an irreversible nonselective MAOI used for major depressive disorder when other antidepressants have not worked adequately. It requires strict management of tyramine intake, contraindicated medications, and washout periods because hypertensive crisis and serotonin syndrome can be life-threatening. It is not generally used as first-line antidepressant therapy because of these safety requirements.
The bottom line
Evidence rating strong. Most-documented uses: treatment-resistant major depressive disorder, atypical depressive symptoms in selected patients, depression not responding to ssris, snris, tcas, or other strategies. 3 sources indexed (2005–2025), with 5 interaction records on file.
Core mechanism
Tranylcypromine irreversibly inhibits MAO-A and MAO-B, reducing metabolism of serotonin, norepinephrine, dopamine, and tyramine. Increased central monoamine availability supports antidepressant effects, while impaired tyramine breakdown can trigger abrupt catecholamine release and hypertensive crisis. Because MAO enzyme activity recovers only after new enzyme synthesis, interaction risk persists after the last dose.2,1
May be taken with or without food. Patients must avoid foods and beverages with significant tyramine content during therapy and for 2 weeks after stopping.
Tranylcypromine is an irreversible MAOI that can sharply reduce tyramine breakdown. High-tyramine foods can then trigger sudden, severe blood-pressure elevation and hypertensive crisis.
Recommendation: Avoid high-tyramine foods while taking Tranylcypromine and continue the MAOI diet for the prescriber-recommended washout period after stopping.
5-HTP increases serotonin synthesis while Tranylcypromine reduces monoamine breakdown. Combining them can cause dangerous serotonergic excess and serotonin syndrome.
Recommendation: Do NOT combine 5-HTP with Tranylcypromine. Use only if the prescriber managing Tranylcypromine explicitly directs it and provides washout instructions.
L-Tryptophan feeds serotonin synthesis while Tranylcypromine reduces serotonin breakdown, increasing risk of serotonin syndrome.
Recommendation: Do NOT combine L-tryptophan with Tranylcypromine unless specifically directed and monitored by the prescriber managing Tranylcypromine.
St. John's Wort has serotonergic effects and is unsafe with irreversible MAOIs.
Recommendation: Do not use St. John's Wort with tranylcypromine.
Rhodiola may have stimulant or monoaminergic effects that are poorly predictable during nonselective MAO inhibition.
Recommendation: Avoid rhodiola while taking tranylcypromine.
Numbered references. Citations throughout the page link here.
Review emphasizes blood pressure monitoring, tyramine avoidance, and interaction washouts.
Combining serotonin-enhancing agents with impaired monoamine metabolism can cause severe serotonin toxicity.
Labeling includes recommended 30 mg/day dosing, maximum 60 mg/day, suicidal thoughts warning, hypertensive crisis warning, and tyramine restrictions.
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