NutriStack
Quetiapine and St. John's Wort, contraindicated.
St. John's Wort is a potent CYP3A4 inducer that can reduce quetiapine plasma concentrations by up to 80%, essentially rendering the medication ineffective. The FDA-approved labeling for quetiapine states that doses may need to be increased up to 5-fold when co-administered with strong CYP3A4 inducers. Loss of quetiapine efficacy can lead to psychiatric decompensation, psychotic relapse, or manic episodes with potentially dangerous consequences.
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
- Quetiapine and St. John's Wort
- Pair type
- Contraindicated
- Evidence (highest tier)
- Strong
- Source citations
- 2 sources
- 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. St. John's Wort is a potent CYP3A4 inducer that can reduce quetiapine plasma concentrations by up to 80%, essentially rendering the medication ineffective. The FDA-approved labeling for quetiapine states that doses may need to be increased up to 5-fold when co-administered with strong CYP3A4 inducers. Loss of quetiapine efficacy can lead to psychiatric decompensation, psychotic relapse, or manic episodes with potentially dangerous consequences.
Mechanism. Hyperforin in St. John's Wort potently activates PXR, inducing CYP3A4 transcription and increasing quetiapine hepatic metabolism. Quetiapine is extensively metabolized by CYP3A4, and enzyme induction can reduce plasma levels below the minimum effective concentration. The FDA label acknowledges this by recommending up to 5-fold dose increases with strong CYP3A4 inducers.
Recommendation. Do NOT take St. John's Wort with quetiapine. This combination is contraindicated due to the risk of complete loss of antipsychotic efficacy. If you are currently taking both, contact your prescriber immediately. Do not abruptly stop St. John's Wort as quetiapine levels will rise over 7-14 days.
Sources (2)
- Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br J Clin Pharmacol. 2006;61(1):58-69. PMID 16390352
- Nicolussi S et al. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226. PMID 31742659
Stack Score
How this pair moves the number.
Effect on the composite score
If both Quetiapine 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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