Coadministration of clozapine and fluvoxamine in psychotic patients - Clinical experience

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clin ical study to gather experience in necessary dosages, plasma levels, side e ffects and clinical efficiency of the coadministration of the two drugs. Ei ghteen 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 a nd 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 pretre atment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The B PRS 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 a fter the study period and 9 of these patients were in clinical remission wh en discharged. Given strict therapeutic drug monitoring, coadministration o f 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 m ight be due to additive effects of the two drugs and/or metabolic interacti on.