title: Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia.
abstract: The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3-6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Policlinico Universitario di Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: D'Arrigo
authors.forename: Gaetana
authors.initials: G
authors.lastname: Migliardi
authors.forename: Vincenza
authors.initials: V
authors.lastname: Santoro
authors.forename: Letterio
authors.initials: L
authors.lastname: Morgante
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Maria
authors.initials: M
authors.lastname: Ancione
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018967:Risperidone / Q000097:blood*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D016666:Fluvoxamine; D018967:Risperidone; D017367:Selective Serotonin Reuptake Inhibitors