DrugPair interaction guide

Sertraline and St. John's Wort

Sertraline (Zoloft) is an antidepressant (SSRI). St. John's Wort is a herbal supplement also used for depression. Combining them raises serotonin levels dangerously.

Written by DrugPair Editorial Team. Updated 16 July 2026.

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Major interaction

Do not combine without direct medical supervision.

What you need to know

Both sertraline and St. John's Wort increase serotonin activity in the brain. Taking them together can lead to serotonin syndrome — a potentially life-threatening condition with agitation, rapid heart rate, high blood pressure, and muscle twitching. St. John's Wort can also reduce sertraline blood levels over time, making the antidepressant less effective.

What to do

Do not start St. John's Wort while taking sertraline or another antidepressant without direct advice from the prescriber who manages it.

Tell your doctor and pharmacist about all herbal supplements you take.

If you want to use a herbal mood supplement, always check with your prescribing doctor first.

When to call your doctor

Agitation, confusion, rapid heartbeat, high temperature, or uncontrolled muscle movements.

Seek emergency care immediately if symptoms are severe.

Severe symptoms? Call 911 (US) or Poison Control 1-800-222-1222

Sources

Sertraline: Drug InformationNIH MedlinePlus. Accessed 2026-07-16.Drug Interactions: What You Should KnowU.S. Food and Drug Administration. Accessed 2026-07-16.

Source databases can disagree or omit an interaction. Report an error.

DrugPair provides educational safety information only and is not a substitute for professional medical advice. Always ask a doctor or pharmacist before changing medicines, supplements, food, drinks, or prescription timing.

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