FLUOXETINE AND NORFLUOXETINE PLASMA-CONCENTRATIONS IN MAJOR DEPRESSION - A MULTICENTER STUDY

Objective: Prior studies examining the relationship between fluoxetine plasma concentrations and response in major depression have either fo und no relationship between plasma concentration and response or sugge sted a curvilinear relationship with a therapeutic window. To elucidat e this relationship, plasma concentrations of fluoxetine, norfluoxetin e, fluxoetine plus norfluoxetine, and fluoxetine/norfluoxetine ratio w ere compared to therapeutic response. Method: A total of 839 patients (577 women, 262 men; mean age=40 years [SD=11]) with a DSM-III-R diagn osis of major affective disorder who were in the course of either majo r depression or bipolar disorder not otherwise specified and had a min imum baseline score of 16 on the 17-item Hamilton Depression Rating Sc ale were initially treated. Response was defined as follows: 1) nonres ponders had less than a 50% reduction from baseline Hamilton depressio n score, 2) nonremitting responders had a 50% or more seduction from b aseline Hamilton depression score but a final scole higher than 7, and 3) remitters had a final Hamilton depression score of 7 ol lower. Pla sma fluoxetine and norfluoxetine concentrations were measured after 8 weeks of fixed-dose treatment at 20 mg/day. Results: Plasma concentrat ion data were available from 615 patients. Plasma concentrations were similar In responders, both remitting and nonremitting (N=411), and no nresponders (N=204) for fluoxetine concentrations, for norfluoxetine c oncentrations, as well as for the sum of fluoxetine and norfluoxetine and for the ratio of fluoxetine to norfluoxetine. No apparent relation ship was observed between plasma drug concentrations and clinical resp onse. Conclusions: Plasma concentrations of fluoxetine and norfluoxeti ne do not appear to be related to clinical outcome and should not be u sed to make treatment decisions.