title: Dose-dependent interaction of paroxetine with risperidone in schizophrenic patients.
abstract: Augmentation with paroxetine (10-40 mg/d) for antipsychotic treatment may improve the negative symptoms in schizophrenic patients but involves a risk of drug-drug interaction. We studied the effects of paroxetine on plasma concentrations of risperidone and 9-hydroxyrisperidone and their clinical symptoms in risperidone-treated patients. Twelve schizophrenic inpatients with prevailingly negative symptoms receiving risperidone 4 mg/d were, in addition, treated with incremental doses of paroxetine for 12 weeks (10, 20, and 40 mg/d for 4 weeks each). Plasma concentrations of risperidone and 9-hydroxyrisperidone were quantified with liquid chromatography-mass spectrometry mass-mass spectrometry together with clinical assessments before and after each phase of the 3 paroxetine doses. Risperidone concentrations during coadministration of paroxetine 10, 20, and 40 mg/d were 3.8-fold (95% confidence interval, 3.2-5.8, P < 0.01), 7.1-fold (95% confidence interval, 5.3-16.5, P < 0.01), and 9.7-fold (95% confidence interval, 7.8-22.5, P < 0.01) higher than that before paroxetine coadministration, respectively. Active moiety (risperidone plus 9-hydroxyrisperidone) concentration was not increased during the paroxetine 10 mg/d (1.3-fold, not significant) or 20 mg/d (1.6-fold, not significant), but were significantly increased by 1.8-fold (95% confidence interval, 1.4-2.7, P < 0.05) during the paroxetine 40 mg/d. Significant improvement in negative symptoms was observed from 10 to 40 mg/d of paroxetine, whereas scores in extrapyramidal side effects during 20 and 40 mg/d of paroxetine were significantly higher than baseline score. This study indicates that paroxetine increases plasma risperidone concentration and active moiety concentration in a dose-dependent manner. Low-dose coadministration of paroxetine with risperidone may be safe and effective in the treatment of schizophrenic patients with negative symptoms.
authors.affiliation: Department of Neuropsychiatry Hirosaki University School of Medicine, Hirosaki, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Saito
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagami
authors.forename: Hanako
authors.initials: H
authors.lastname: Furukori
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D017374:Paroxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood*; D018967:Risperidone / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy
chemical_list: D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D017374:Paroxetine; D018967:Risperidone; D000068882:Paliperidone Palmitate