No effect of reboxetine on plasma concentrations of clozapine, risperidone, and their active metabolites

The effect of reboxetine on steady-state plasma concentrations of the atypical antipsychotics clozapine and risperidone was studied in 14 patients with schizophrenia or schizoaffective disorder with associated depressive symptoms. Seven patients stabilized on clozapine therapy (250–500 mg/day) and seven receiving risperidone (4–6 mg/day) were given additional reboxetine (8 mg/day). After 4 weeks of reboxetine therapy, mean plasma concentrations of clozapine, norclozapine, and risperidone active moiety (sum of concentrations of risperidone and 9-hydroxyrisperidone) increased slightly but not significantly by 5%, 2%, and 10%, respectively. The mean plasma clozapine/norclozapine and risperidone/9-hydroxyrisperidone ratios were not modified during reboxetine treatment. Reboxetine coadministration with either clozapine or risperidone was well tolerated. These findings indicate that reboxetine has minimal effects on the metabolism of clozapine and risperidone and may be added safely to patients receiving maintenance treatment with these two antipsychotics.