title: Plasma risperidone concentrations during combined treatment with sertraline.
abstract: The effect of sertraline on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was studied in 11 patients with schizophrenia or schizoaffective disorder. To treat concomitant depressive symptoms, additional sertraline, at the dose of 50 mg/d, was administered for 4 weeks to patients stabilized on risperidone (4-6 mg/d). Mean plasma concentrations of risperidone, 9-OH-risperidone, and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) did not change significantly during combined treatment with sertraline. At the end of week 4, sertraline dosage was adjusted in some patients on the basis of the individual response and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the 4 patients who were still receiving the initial sertraline dose, but concentrations were slightly but not significantly increased (by a mean 15% over pretreatment) in the subgroup of 5 subjects treated with a final dose of 100 mg/d. In the 2 patients receiving the highest dose of sertraline, 150 mg/d, at week 8 total plasma risperidone concentrations were increased by 36% and 52%, respectively, as compared with baseline values. Sertraline coadministration with risperidone was well tolerated, and no patient developed extrapyramidal symptoms. These findings indicate that sertraline at dosages up to 100 mg/d is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of sertraline may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of sertraline on CYP2D6-mediated 9-hydroxylation of risperidone.
authors.affiliation: Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy. espina@unime.it
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
authors.forename: Concetta
authors.initials: C
authors.lastname: D'Arrigo
authors.forename: Gaetana
authors.initials: G
authors.lastname: Migliardi
authors.forename: Letterio
authors.initials: L
authors.lastname: Morgante
authors.forename: Rocco
authors.initials: R
authors.lastname: Zoccali
authors.forename: Maria
authors.initials: M
authors.lastname: Ancione
authors.forename: Aldo
authors.initials: A
authors.lastname: Madia
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000097:blood; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011618:Psychotic Disorders / Q000188:drug therapy; D011743:Pyrimidines / Q000097:blood; D018967:Risperidone / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy; D012702:Serotonin Antagonists / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020280:Sertraline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D000068882:Paliperidone Palmitate; D011743:Pyrimidines; D018967:Risperidone; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline