Per FDA label
Trazodone and MAOIs (monoamine oxidase inhibitors)
Combining trazodone with an MAOI carries a serious, well-documented serotonin syndrome risk. A washout period of roughly 14 days is generally required between the two.
Editorially reviewed
Key points
- One of the most serious documented trazodone interactions
- A roughly two-week washout is typically required in either direction
- Never combine without explicit prescriber direction
Monoamine oxidase inhibitors (MAOIs) — including phenelzine, tranylcypromine, and selegiline — work through a different mechanism than trazodone but ultimately increase serotonin and other neurotransmitter activity. Combining them with trazodone significantly raises the risk of serotonin syndrome, a potentially life-threatening reaction.
Prescribers typically require a washout period of about 14 days after stopping an MAOI before starting trazodone, and vice versa, to let the first drug clear the body. Never combine these medications without explicit direction from the prescriber managing both.
Seek urgent care if you notice:
- Fever, agitation, or confusion after starting either medication
- Muscle rigidity or uncontrollable shivering
- Rapid heartbeat with sweating
Not medical advice. Always tell your prescriber and pharmacist about every medication, supplement, and substance you use so they can check for interactions specific to your situation.
