EFFECT OF FLUOXETINE ON THE PLASMA-CONCENTRATIONS OF CLOZAPINE AND ITS MAJOR METABOLITES IN PATIENTS WITH SCHIZOPHRENIA

The effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites was studied in 10 schizophrenic patients with r esidual negative symptoms. Patients stabilized on clozapine therapy (2 00-450 mg/day) received additional fluoxetine (20 mg/day) for eight co nsecutive weeks. During fluoxetine administration, mean plasma concent rations of clozapine, norclozapine and clozapine N-oxide increased sig nificantly by 58%, 36% and 38%, respectively. There was no difference in negative symptomatology, as measured by the Scale for Assessment of Negative Symptoms, and the drug combination was generally well tolera ted. The concomitant elevation in plasma levels of clozapine and its m ajor metabolites suggests that fluoxetine inhibits the metabolism of c lozapine by affecting pathways other than N-demethylation and N-oxidat ion. Close monitoring of clinical response and, possibly, plasma cloza pine levels is recommended whenever fluoxetine is given to patients st abilized on clozapine therapy. Int Clin Psychopharmacol 13:141-145 (C) 1998 Lippincott-Raven Publishers.