ArticlesPlasma Concentrations of Risperidone and 9-Hydroxyrisperidone During Combined Treatment With ParoxetineSpina, Edoardo*† ; Avenoso, Angela* ; Facciolà, Gabriella* ; Scordo, Maria Gabriella* ; Ancione, Maria†; Madia, Aldo†Author Information *Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, †Centers of Mental Health, Azienda USL 5, Messina, Italy Received November 1, 2000; accepted January 30, 2001. Address correspondence and reprint requests to Prof. Edoardo Spina, Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Policlinico Universitario, Torre Biologica, 5° piano, Via Consolare Valeria, 98125 Messina, Italy; E-mail: [email protected]http://www.unime.it Therapeutic Drug Monitoring: June 2001 - Volume 23 - Issue 3 - p 223-227 Buy Abstract The effects of paroxetine on steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) were studied in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized using risperidone therapy (4–8 mg/d) also received paroxetine (20 mg/d) for 4 weeks. During paroxetine administration, mean plasma concentrations of risperidone increased significantly (P < 0.01), whereas levels of 9-OH-risperidone decreased slightly but not significantly. After 4 weeks of paroxetine treatment, the sum of the concentrations of risperidone and 9-OH-risperidone (active moiety) increased significantly by 45% (P < 0.05) over baseline. The mean plasma risperidone/9-OH-risperidone ratio was also significantly modified (P < 0.001) during paroxetine treatment. The drug combination was generally well tolerated with the exception of one patient who developed Parkinsonian symptoms in the second week of adjunctive therapy. In this patient total plasma levels of risperidone and its active metabolite increased by 62% during paroxetine co-administration. The authors' findings indicate that paroxetine, a potent inhibitor of CYP2D6, may impair the elimination of risperidone, primarily by inhibiting CYP2D6-mediated 9-hydroxylation and to a lesser extent by simultaneously affecting the further metabolism of 9-OH-risperidone or other pathways of risperidone biotransformation. Careful clinical observation and possibly monitoring of plasma risperidone levels may be useful whenever paroxetine is co-administered with risperidone. © 2001 Lippincott Williams & Wilkins, Inc.