NutriStack
St. John's Wort and Sumatriptan, a caution.
St. John's wort has serotonergic antidepressant activity and has been linked to clinically important interactions with antidepressant drugs. Sumatriptan also acts on serotonin receptors, so combining it with St. John's wort may increase the risk of serotonin toxicity, even though direct case evidence for this exact pair is limited. Watch for agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- St. John's Wort and Sumatriptan
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. St. John's wort has serotonergic antidepressant activity and has been linked to clinically important interactions with antidepressant drugs. Sumatriptan also acts on serotonin receptors, so combining it with St. John's wort may increase the risk of serotonin toxicity, even though direct case evidence for this exact pair is limited. Watch for agitation, tremor, sweating, diarrhea, clonus, fever, or confusion.
Mechanism. St. John's wort constituents can inhibit reuptake of serotonin and other monoamines, increasing serotonergic tone. Sumatriptan activates 5-HT1B/1D receptors; combining serotonergic mechanisms can increase receptor overstimulation risk in susceptible patients.
Recommendation. Avoid St. John's wort if you use sumatriptan for migraines. If you already take St. John's wort, stop it and discuss safer migraine and mood-support options with your prescriber. Seek urgent care if serotonin-toxicity symptoms appear after overlapping use.
Sources (3)
- Lantz MS, Buchalter E, Giambanco V. St. John's wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol. 1999;12(1):7-10. PMID 10447148
- Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798. PMID 19719333
- Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010;50(6):1089-1099. PMID 20618823
Stack Score
How this pair moves the number.
Effect on the composite score
If both St. John's Wort and Sumatriptan are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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