Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service.

Therapeutic drug monitoring data of the new atypical neuroleptic drug olanzapine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of concentration/daily dose (C/D; ng/mL per mg/d) of olanzapine was compared in three groups: patients treated with olanzapine (n = 134), patients treated with olanzapine plus fluvoxamine (n = 10) concomitantly, and patients treated with olanzapine plus sertraline (n = 21) concomitantly. No significant difference was seen between the olanzapine and the olanzapine plus sertraline groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the mean 2.3-fold higher than patients receiving olanzapine without additional fluvoxamine. This indicated that fluvoxamine inhibits the metabolism of olanzapine, probably because of inhibition of cytochrome P450 (CYP) 1A2, whereas sertraline is unlikely to interfere with the metabolism of olanzapine. Combination therapy of olanzapine and fluvoxamine should be used cautiously, and therapeutic drug monitoring should be instituted to avoid olanzapine-induced adverse effects or intoxications.