NutriStack
Desvenlafaxine and St. John's Wort, contraindicated.
St. John's Wort has antidepressant-like serotonergic activity and is a major herb-drug interaction trigger. Combining it with desvenlafaxine can add serotonin reuptake effects and increase the risk of serotonin syndrome. St. John's Wort products vary widely in hyperforin content, making the interaction hard to predict.
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
- Desvenlafaxine and St. John's Wort
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 3 sources
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. St. John's Wort has antidepressant-like serotonergic activity and is a major herb-drug interaction trigger. Combining it with desvenlafaxine can add serotonin reuptake effects and increase the risk of serotonin syndrome. St. John's Wort products vary widely in hyperforin content, making the interaction hard to predict.
Mechanism. Hyperforin-containing St. John's Wort inhibits monoamine reuptake and activates pregnane X receptor pathways that induce CYP3A4 and P-glycoprotein. Desvenlafaxine inhibits SERT and NET, so the main concern is additive serotonergic pharmacodynamics.
Recommendation. Do not combine St. John's Wort with desvenlafaxine. Allow at least a 2-week washout after stopping St. John's Wort before starting or restarting desvenlafaxine unless your prescriber gives a different plan. Avoid other serotonergic substances during the transition.
Sources (3)
- Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13):1777-1798. PMID 19719333
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
- Fanelli D, Weller G, Liu H. New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations. Neurol Int. 2021;13(4):497-509. PMID 34698218
Stack Score
How this pair moves the number.
Effect on the composite score
If both Desvenlafaxine 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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