NutriStack
Duloxetine and St. John's Wort, contraindicated.
Combining duloxetine (an SNRI) with St. John's Wort creates a serious risk of serotonin syndrome. Both agents increase synaptic serotonin through different mechanisms. St. John's Wort may also induce CYP1A2, which is the primary enzyme metabolizing duloxetine, creating complex and dangerous pharmacokinetic-pharmacodynamic interactions.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- Duloxetine and St. John's Wort
- Pair type
- Contraindicated
- Evidence (highest tier)
- Strong
- Source citations
- 1 source
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Strong evidence
Contraindicated
What is happening. Combining duloxetine (an SNRI) with St. John's Wort creates a serious risk of serotonin syndrome. Both agents increase synaptic serotonin through different mechanisms. St. John's Wort may also induce CYP1A2, which is the primary enzyme metabolizing duloxetine, creating complex and dangerous pharmacokinetic-pharmacodynamic interactions.
Mechanism. Duloxetine blocks SERT and NET. St. John's Wort independently inhibits serotonin reuptake via hyperforin and may inhibit MAO. The combined serotonergic mechanisms create dangerous serotonin excess. Additionally, St. John's Wort may induce CYP1A2, altering duloxetine plasma levels unpredictably.
Recommendation. Do not take St. John's Wort with duloxetine under any circumstances. This combination poses dual risks: serotonin syndrome and unpredictable changes in duloxetine levels. Seek alternative mood support options.
Sources (1)
Stack Score
How this pair moves the number.
Effect on the composite score
If both Duloxetine and St. John's Wort are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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