MAOIs + SSRIs
MAOIs + SSRIs: the short answerCombining an MAOI with an SSRI is a textbook cause of severe serotonin syndrome — one of the most dangerous antidepressant interactions there is. Switching between them requires a washout period of weeks, and mixing them needs emergency care.
Why it’s dangerous
MAOIs shut down the enzyme that breaks down serotonin, while SSRIs block its reuptake — so serotonin accumulates from both directions and can reach toxic levels quickly. Because older MAOIs bind the enzyme irreversibly, the danger persists for about two weeks after the last MAOI dose, which is why switches require a supervised washout.
What happens
- Serotonin syndrome: severe agitation, confusion, sweating, diarrhea
- Very high fever, muscle rigidity, and jerking movements
- Dangerous spikes in blood pressure and heart rate
- Seizures, coma, and death in severe cases
Warning signs
- Rapid onset of agitation, tremor, and sweating after a dose
- Fever climbing above ~38.5°C/101°F with stiff, jerking muscles
- Severe headache or chest pounding (blood pressure surge)
What to do
- Call emergency services — serotonin syndrome can escalate within hours
- Do not take further doses of either drug
- Never start, stop, or swap between an MAOI and an SSRI without a prescriber managing the washout (typically 2 weeks, 5 for fluoxetine)
- Tell every prescriber and pharmacist you see that you take an MAOI