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 atypi cal antipsychotics clozapine and risperidone was studied in 14 patients wit h schizophrenia or schizoaffective disorder with associated depressive symp toms. Seven patients stabilized on clozapine therapy (250-500 mg/day) and s even receiving risperidone (4-6 mg/day) were given additional reboxetine (R mg/day). After 4 weeks of reboxetine therapy, mean plasma concentrations o f clozapine, norclozapine, and risperidone active moiety (sum of concentrat ions of risperidone and 9-hydroxyrisperidone) increased slightly but not si gnificantly by 5%, 2%, and 10%, respectively. The mean plasma clozapine/nor clozapine and risperidone/9-hydroxyrisperidone ratios were not modified dur ing 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.