Is St. John's Wort Safe with Amitriptyline?
Free · No account · based on published sources including NIH ODS, FDA drug labels, and peer-reviewed literature
Avoid combining St. John's Wort with tricyclic antidepressants. If you are self-treating depression with St. John's Wort alongside a prescribed antidepressant, inform your doctor. Do not stop either medication abruptly without guidance.
Why this interaction occurs
St. John's Wort induces CYP3A4 and CYP2C19, which are involved in amitriptyline metabolism. This reduces amitriptyline plasma concentrations, potentially causing treatment failure. Additionally, both agents have serotonergic activity, presenting an elevated risk of serotonin-related adverse effects.
Evidence
Evidence level: moderate.
Reported safety data
The FDA’s adverse event reporting system (FAERS) has received 93,704 reports mentioning Amitriptyline. This reflects reported cases involving the medication in general — not confirmed causation, and not specific to the Amitriptyline + supplement combination on this page.
FAERS reports are voluntary and cannot prove that a drug caused an event. Do not use report counts to assess the safety of this specific drug-supplement pair.
Frequently asked questions
Related interactions
All St. John's Wort interactions → · All Amitriptyline interactions →
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Educational only — not medical advice.
Always confirm with your doctor or pharmacist.