- Design
- Retrospective therapeutic drug monitoring cohort
- Population
- Patients on quetiapine with or without valproate
- Primary outcome
- Dose-corrected plasma concentrations of quetiapine and N-desalkylquetiapine
- Effect
- C/D ratio -16.9% (quetiapine) and -23.7% (metabolite) with valproate
This retrospective therapeutic drug monitoring study compared dose-corrected plasma concentrations of quetiapine and its active metabolite N-desalkylquetiapine in patients with and without valproate co-medication. Published in Therapeutic Drug Monitoring on 16 October 2026.
With valproate, the concentration-to-dose ratio was 17% lower for quetiapine and 24% lower for N-desalkylquetiapine. The quetiapine effect was significant in women of all ages but not in men; the metabolite effect was seen in both sexes, and fell further with higher valproate doses.
Valproate is usually thought of as an enzyme inhibitor, so a fall in quetiapine levels is not intuitive. Quetiapine and valproate are a very common combination in bipolar disorder.
The effect is moderate and the study is observational, with the mechanism unclear. It is a reason to review response, not to change doses pre-emptively.
- Consider valproate as a possible cause when a woman's response to quetiapine falls after valproate is added
- Use quetiapine levels, where available, before increasing the dose
- Do not reduce quetiapine pre-emptively when adding valproate
- Recheck response after any change to valproate dose
Why it matters
A common psychiatric combination may lower the antipsychotic exposure in a way prescribers do not expect.
Don't overread it
The sex difference came from a subgroup analysis and needs confirmation.
The statistics, in plain English
A 17% fall in concentration-to-dose ratio means that, for the same dose, blood levels were about a sixth lower. The correlation with valproate dose (rs -0.15) was weak.
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