title: Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia.
abstract: The effect of mirtazapine on steady-state plasma concentrations of the newer atypical antipsychotics clozapine, risperidone and olanzapine was investigated in 24 patients with chronic schizophrenia. In order to treat residual negative symptoms, additional mirtazapine (30 mg per day) was administered for six consecutive weeks to nine patients stabilized on clozapine therapy (200-650 mg per day), eight on risperidone (3-8 mg per day) and seven on olanzapine (10-20mg per day). There were only minimal and statistically insignificant changes in mean plasma concentrations of clozapine and its metabolite norclozapine, risperidone and its metabolite 9-hydroxyrisperidone, and olanzapine during the study period. Mirtazapine co-administration with either clozapine, risperidone or olanzapine was well tolerated. In the overall sample, a slight improvement in negative symptomatology, as assessed by the Scale for Assessment of Negative Symptoms, was observed at final evaluation (P<0.01) and six patients (two in each treatment group) were classified as responders. While double-blind, controlled studies are needed to evaluate the potential clinical benefits of mirtazapine in chronic schizophrenia, our findings indicate that mirtazapine has a negligible effect on the metabolism of clozapine, risperidone and olanzapine and can be added safely to an existing treatment with these antipsychotics.
authors.affiliation: Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Messina, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Zoccali
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Muscatello
authors.forename: Diletta La
authors.initials: DL
authors.lastname: Torre
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malara
authors.forename: Andrea
authors.initials: A
authors.lastname: Canale
authors.forename: Domenico
authors.initials: D
authors.lastname: Crucitti
authors.forename: Concetta
authors.initials: C
authors.lastname: D'Arrigo
authors.forename: Edoardo
authors.initials: E
authors.lastname: Spina
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D003024:Clozapine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D000078785:Mirtazapine; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D008803:Mianserin; D000078785:Mirtazapine; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine