Inhibition of Risperidone Metabolism by Fluoxetine in Patients With Schizophrenia: A Clinically Relevant Pharmacokinetic Drug Interaction

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Abstract
The effect of fluoxetine on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was evaluated in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized on risperidone (4–6 mg/day) received additional fluoxetine (20 mg/day) to treat concomitant depression. One patient dropped out after 1 week due to the occurrence of akathisia associated with markedly increased plasma risperidone concentrations. In the other subjects, mean plasma concentrations of risperidone increased during fluoxetine administration from 12 ± 9 ng/mL at baseline to 56 ± 31 at week 4 (p p