Valproate lowers quetiapine levels, mainly in women

Design

Retrospective therapeutic drug monitoring cohort

Population

Patients on quetiapine with or without valproate

Primary outcome

Concentration-to-dose ratio of quetiapine and norquetiapine

Effect

Quetiapine −16.9% (women only); norquetiapine −23.7% (all)

A retrospective therapeutic drug monitoring study in Therapeutic Drug Monitoring (16 October) compared dose-corrected quetiapine concentrations in patients with and without co-prescribed valproate.

Valproate was associated with a 17% lower concentration-to-dose ratio for quetiapine and a 24% lower ratio for its active metabolite, norquetiapine. The quetiapine effect was seen only in women, in both age groups studied; the metabolite effect was seen in everyone and grew with valproate dose.

Valproate is usually thought of as an enzyme inhibitor, so a fall in quetiapine is counter-intuitive. The clinical point is modest: in a woman whose response to quetiapine fades after valproate is added, a level may explain it.

• Valproate was associated with about 17% lower dose-corrected quetiapine levels
• The effect on quetiapine was seen in women, not men
• Norquetiapine levels fell by about 24% in all patients
• Consider a quetiapine level if response falls after valproate is added

Why it matters

It runs against the expectation that valproate raises the levels of co-prescribed drugs.

Don't overread it

Retrospective and concentration-based — it did not measure clinical response.

The statistics, in plain English

A concentration-to-dose ratio adjusts the measured level for the dose taken, so a lower ratio means the body handles each milligram differently. The sex difference rests on a subgroup interaction (P = 0.007).

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.