St. John's Wort is marketed as a mood-support supplement, but it has real pharmacological activity: it increases serotonin activity (risking serotonin syndrome when combined with trazodone) and induces the CYP3A4 liver enzyme, which can speed up trazodone's breakdown and reduce its effectiveness. This is one of the more clinically significant supplement interactions on this list, precisely because it's widely available without a prescription.
Trazodone and St. John's Wort
This popular herbal supplement is both serotonergic and a CYP3A4 inducer, giving it a double interaction risk with trazodone: serotonin syndrome and reduced trazodone levels.
Editorially reviewed
Key points
- Both serotonergic and a CYP3A4 inducer — a double interaction
- Widely available over the counter without medical guidance
- Tell your prescriber if you take this supplement
Seek urgent care if you notice:
- Agitation, tremor, or fever if combined
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.