MajorAntidepressants. Other antidepressants of herbal origin×Selective serotonin reuptake inhibitors (SSRIs)
Updated · Methodology
Mechanism
St John's wort contains hypericin and hyperforin – serotonergic activators and strong inducers of CYP3A4 and P-glycoprotein. On sertraline (SSRI), serotonergic activity adds up; serotonin syndrome risk arises.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever above 38.5 °C.
Management
The combination is not prescribed. Warn the patient that St John's wort is not a neutral herbal supplement but an active serotonergic with dozens of drug interactions. CYP3A4 induction persists for 1–2 weeks after stopping the herb.
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Sources
- PubMed: Serotonin syndrome with St. John's wort and SSRIs: a systematic review (2018)
- AEMPS: Ficha técnica: Sertralina (nº registro 66057), sección 4.5 (2025)– AEMPS, CIMA, nº registro 66057, sección 4.5