Coadministration of Clozapine and Fluvoxamine in Psychotic Patients - Clinical Experience

Abstract

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clinical study to gather experience in necessary dosages, plasma levels, side effects and clinical efficiency of the coadministration of the two drugs. Eighteen psychotic patients were studied. 50 mg FLUVOX were given throughout the study period, while the CLOZ dosage was increased individually (week 5: 96.9 + 37.2 mg). After 5 weeks the plasma concentrations were as follows: CLOZ 252 ± 174 ng/ ml, N-desmethylclozapine (DM-CLOZ) 143 ± 74 ng/ml and clozapine N-oxide (CLOZ N-OX) 30 ± 14 ng/ml. There were no differences in side effects, especially sedation, after 5 weeks compared to the pretreatment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The BPRS scores dropped continuously until week 5 (pretreatment: 53.3 ± 13.4; week 5: 33.2 ± 12.9) and 5 patients were considered treatment responders (BPRS reduction > 50 %). Ten patients continued the combination treatment after the study period and 9 of these patients were in clinical remission when discharged. Given strict therapeutic drug monitoring, coadministration of FLUVOX and CLOZ seems to be a safe and efficient treatment strategy with a low occurrence of the side effects associated with CLOZ treatment. This might be due to additive effects of the two drugs and/or metabolic interaction.