ARE FLUOXETINE PLASMA-LEVELS RELATED TO OUTCOME IN OBSESSIVE-COMPULSIVE DISORDER

Objective: In obsessive-compulsive disorder, the relationship between blood levels of serotonin reuptake inhibitors and clinical outcome is unclear. In a multicenter trial, the authors examined the relationship between steady state plasma levels of fluoxetine and norfluoxetine (d etermined after 7 weeks of treatment), and their sum, and clinical out come. Method: Ratings of symptom severity of obsessive-compulsive diso rder (Yale-Brown Obsessive Compulsive Scale scores) were obtained at b aseline and after 13 weeks for 200 adult outpatients with moderately s evere obsessive-compulsive disorder treated with fluoxetine doses of 2 0 mg/day (N=68), 40 mg/day (N=64), and 60 mg/day (N=68). Results: Mean plasma levels of fluoxetine and norfluoxetine were statistically sign ificantly higher with higher dose. Statistical analyses revealed no si gnificant relationship for plasma level of either molecule or their su m in predicting endpoint percent change in obsessive-compulsive scores . Plasma levels of patients with a marked response (decrease of 50% or more in obsessive-compulsive score) did not differ significantly from those of nonresponders (less than a 25% decrease in obsessive-compuls ive score). No hint was seen of a therapeutic window or a relationship limited to one gender or within the lowest dose group (20 mg/day). Ho wever, sins S-norfluoxetine is a much more potent serotonin reuptake i nhibitor than R-norfluoxetine, the absence of chiral (stereospecific) assays in this study limits the results. Conclusions: Steady state pla sma levels of fluoxetine and norfluoxetine are not related to clinical outcome in patients with obsessive-compulsive disorder. Individual pa tients can be told only that the optimum dose of fluoxetine for them w ill be the dose that produces the largest therapeutic effect with the smallest side effect burden. Future studies should examine the predict ive utility of measures of serotonergic neuronal function and, if plas ma levels of norfluoxetine are examined, the use of chiral assays.