title: Olanzapine and clozapine differently affect sleep in patients with schizophrenia: results from a double-blind, polysomnographic study and review of the literature.
abstract: Schizophrenia is associated with impaired sleep continuity. The second generation antipsychotics clozapine and olanzapine have been reported to improve sleep continuity but also to rarely induce restless legs syndrome (RLS). The aims of this randomized double-blind study were to compare the effects of clozapine and olanzapine on sleep and the occurrence of RLS. Therefore, polysomnographies were recorded and RLS symptoms were assessed in 30 patients with schizophrenia before and after 2, 4 and 6 weeks of treatment with either clozapine or olanzapine. Treatment with both antipsychotics increased total sleep time, sleep period time and sleep efficiency and decreased sleep onset latency. These changes were similar in both groups, occurred during the first 2 treatment weeks and were sustained. For example, sleep efficiency increased from 83% (olanzapine) and 82% (clozapine) at baseline to 95% at week 2 and 97% at week 6 in both treatment groups. Sleep architecture was differently affected: clozapine caused a significantly stronger increase of stage 2 sleep (44%) than olanzapine (11%) but olanzapine a significantly stronger increase of REM-sleep. Olanzapine caused an 80% increase of slow wave sleep whereas clozapine caused a 6% decrease. No patient reported any of 4 RLS defining symptoms at baseline. During treatment, 1 patient of each group reported at one visit all 4 symptoms, i.e. met the diagnosis of an RLS. In conclusion, sleep continuity similarly improved and sleep architecture changed more physiologically with olanzapine. Neither of the antipsychotics induced RLS symptoms that were clinically relevant.
authors: Department of Psychiatry, University of Leipzig, Leipzig, Germany; Max Planck Institute of Psychiatry, Munich, Germany. Electronic address: Michael.Kluge@medizin.uni-leipzig.de.
authors: Michael
authors: M
authors: Kluge
authors: Lilly Deutschland GmbH, Medical Department, Bad Homburg, Germany.
authors: Alexander
authors: A
authors: Schacht
authors: Department of Psychiatry, University of Leipzig, Leipzig, Germany.
authors: Hubertus
authors: H
authors: Himmerich
authors: Department of Psychiatry, University of Leipzig, Leipzig, Germany.
authors: Christine
authors: C
authors: Rummel-Kluge
authors: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Germany.
authors: Peter M
authors: PM
authors: Wehmeier
authors: Max Planck Institute of Psychiatry, Munich, Germany.
authors: Mira
authors: M
authors: Dalal
authors: Fachklinik St. Marienstift, Center for Psychiatric and Psychotherapeutic Treatment for Traumatized Males, Neuenkirchen, Germany.
authors: Dunja
authors: D
authors: Hinze-Selch
authors: Frankenalb-Klinik, District Hospital of Psychiatry, Psychotherapy, Psychosomatics and Addiction Rehabilitation, Engelthal, Germany.
authors: Thomas
authors: T
authors: Kraus
authors: Department of Child and Adolescent Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Germany.
authors: Ralf W
authors: RW
authors: Dittmann
authors: Max Planck Institute of Psychiatry, Munich, Germany; Klinikum Ingolstadt, Center of Mental Health, Ingolstadt, Germany.
authors: Thomas
authors: T
authors: Pollmächer
authors: Klinikum Ingolstadt, Center of Mental Health, Ingolstadt, Germany.
authors: Andreas
authors: A
authors: Schuld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D016208:Databases, Factual / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D017286:Polysomnography; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D000077152:Olanzapine
keywords: Clozapine; Olanzapine; REM; RLS; Restless legs syndrome; Sleep; Slow-wave-sleep