CriticalSelective serotonin reuptake inhibitors×Antidepressant, irreversible non-selective monoamine oxidase inhibitor (MAO-A and MAO-B)
Updated · Methodology
Mechanism
Phenelzine irreversibly inhibits MAO; fluoxetine blocks serotonin reuptake. Combined use causes synaptic serotonin accumulation and serotonin syndrome: hyperthermia, myoclonus, agitation, coma. FDA Nardil Section 4 strict contraindication. A 5-week washout is required between fluoxetine and phenelzine (due to norfluoxetine's long T½).
Symptoms
Within hours: agitation, confusion, tachycardia, hypertension, hyperthermia, tremor, myoclonus, hyperreflexia. Severe cases – seizures, coma, rhabdomyolysis, DIC.
Management
Combination contraindicated. Allow 5-week washout between stopping fluoxetine and starting phenelzine. Allow 2-week washout between stopping phenelzine and starting any SSRI (MAO resynthesis time).
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Nardil (phenelzine sulfate) prescribing information (2009)– FDA Nardil label, Section 4 Contraindications; DailyMed setid 513a41d0-37d4-4355-8a6d-a2c643bce6fa
- AEMPS: Ficha técnica: Fluoxetina (nº registro 63499), sección 4.5 (2026)– AEMPS, CIMA, nº registro 63499, revisión 10/2026, sección 4.5