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 olanz apine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of co ncentration/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 treat ed with olanzapine plus sertraline (n = 21) concomitantly. No significant d ifference was seen between the olanzapine and the olanzapine plus sertralin e groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the mean 2.3-fold higher than patients receiving olanza pine, without additional fluvoxamine. This indicated that fluvoxamine inhib its the metabolism of olanzapine, probably because of inhibition of cytochr ome P450 (CYP) 1A2, whereas sertraline is unlikely to interfere with the me tabolism of olanzapine. Combination therapy of olanzapine and fluvoxamine s hould be used cautiously, and therapeutic drug monitoring should be institu ted to avoid olanzapine-induced adverse effects or intoxications.