Effect of valproate on olanzapine plasma concentrations in patients with bipolar or schizoaffective disorder

The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 +/- 9.7 ng/mL at baseline to 27.4 +/- 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 +/- 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects.