Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects.

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% (0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng…