Download PDF
Pharmacopsychiatry 2004; 37(4): 157-162
DOI: 10.1055/s-2004-827170
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Subchronic Effects of Olanzapine on Sleep EEG in Schizophrenic Patients with Predominantly Negative Symptoms

M. J. Müller1 , W. Rossbach1 , K. Mann1 , J. Röschke1 , F. Müller-Siecheneder1 , M. Blümler1 , H. Wetzel1 , H. Ruß2 , R. W. Dittmann2 , O. Benkert1
  • 1Department of Psychiatry, University of Mainz, Mainz, Germany
  • 2Lilly Deutschland GmbH, Bad Homburg, Germany
Parts of the present study were sponsored by Lilly Deutschland GmbH
Further Information

Publication History

Received: 20.3.2002 Revised: 6.6.2002

Accepted: 30.4.2003

Publication Date:
01 July 2004 (online)

Also available at
    Permissions and Reprints

Background: It is well known that sleep disturbance is an integral symptom of schizophrenia. In recent studies, a deficit of delta sleep has been observed in schizophrenic patients. Antipsychotic drugs with serotonin (5-HT2) receptor-antagonistic properties are considered to have delta sleep promoting effects. We have investigated the effects of subchronic olanzapine treatment on sleep EEG in schizophrenic patients. Methods: The effects of administration of olanzapine (15 to 20 mg) on sleep were studied for four weeks in 10 male, drug-free patients suffering from schizophrenia with predominantly negative symptoms. Conventional sleep EEG parameters were investigated at baseline and after treatment with olanzapine for four weeks. Additionally, spectral power analysis of the EEG signal in distinct frequency bands was computed for different sleep stages. Psychopathology (PANSS, HAMD-17, HAMA) and side effects were assessed weekly. Results: All patients improved, as measured by PANSS global scores. Compared to baseline, there was a significant improvement of parameters of sleep efficiency and an increase of delta sleep as well as REM sleep. Regarding spectral power values, no significant differences between baseline and treatment conditions were found. Conclusions: Sleep improvement was due to parameters of sleep efficiency and delta sleep, which may be related to serotonin antagonistic properties of olanzapine.

References

  • 1 American Psychiatric A ssociation. Diagnostic and Statistical Manual of Mental Disorders. 4th ed Washington, DC; American Psychiatric Press 1994
    Search in Google Scholar
  • 2 Baptista T, Kin N M, Beaulieu S, de Baptista E A. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives.  Pharmacopsychiatry. 2002;  35 205-219
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Benca R M, Obermeyer W H, Thisted R A, Gillin J C. Sleep and psychiatric disorders. A meta-analysis.  Arch Gen Psychiat. 1992;  49 651-668
    CrossrefPubMedSearch in Google Scholar
  • 4 Borbély A, Trachsel L, Tobler I. Effects of ritanserine on sleep stages and sleep EEG in the rat.  Eur J Pharmacol. 1988;  156 275-278
    CrossrefPubMedSearch in Google Scholar
  • 5 Bymaster F P, Calligaro D O, Falcone J F, Marsh R D, Moore N A, Tye N C, Seeman P, Wong D T. Radioreceptor binding profile of the atypical antipsychotic olanzapine.  Neuropsychopharmacology. 1996;  14 87-96
    PubMedSearch in Google Scholar
  • 6 Driver H S, Flanigan M J, Bentley A J, Luus H G, Shapiro C M, Mitchel D. The influence of ipsapirone, a 5-HT1A agonist, on sleep patterns of healthy subjects.  Psychopharmacology. 1995;  117 186-192
    PubMedSearch in Google Scholar
  • 7 Dugovic C, Wauquier A, Janssen P A. Differential effects of the new antipsychotic risperidone on sleep and wakefulness in the rat.  Neuropharmacology. 1989;  28 1431-1433
    CrossrefPubMedSearch in Google Scholar
  • 8 Eschweiler G W, Bartels M, Langle G, Wild B, Gaertner I, Nickola M. Heart-rate variability (HRV) in the ECG trace of routine EEGs: fast monitoring for the anticholinergic effects of clozapine and olanzapine?.  Pharmacopsychiatry. 2002;  35 96-100
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Feinberg I, Braum N, Koresko R L, Gottlieb F. Stage 4 sleep in schizophrenia.  Arch Gen Psychiat. 1969;  21 262-266
    PubMedSearch in Google Scholar
  • 10 Frieboes R -M, Murck H, Antoijevic I, Kraus T, Hinze-Selch D, Pollmächer T, Steiger A. Characterization of the sigma ligand panamesine, a potential antipsychotic, by immune response in patients with schizophrenia and by sleep-EEG changes in normal controls.  Psychopharmacology. 1999;  141 107-110
    CrossrefPubMedSearch in Google Scholar
  • 11 Ganguli R, Reynolds C F, Kupfer D J. EEG sleep in young, never medicated, schizophrenic patients: a comparison with delusional and nondelusional depressives and with healthy controls.  Arch Gen Psychiat. 1987;  44 36-45
    PubMedSearch in Google Scholar
  • 12 Hiatt J F, Floyd T C, Katz P H, Feinberg I. Further evidence of abnormal NREM sleep in schizophrenia.  Arch Gen Psychiat. 1985;  42 797-802
    PubMedSearch in Google Scholar
  • 13 Hinze-Selch D, Mullington J, Orth A, Lauer C J, Pollmächer T. Effects of clozapine on sleep: a longitudinal study.  Biol Psychiat. 1997;  42 260-266
    CrossrefPubMedSearch in Google Scholar
  • 14 Idzikowski C, Mills F J, Glennard R. 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep.  Brain Res. 1986;  378 164-168
    CrossrefPubMedSearch in Google Scholar
  • 15 Keshavan M S, Reynolds C F, Kupfer D J. Electroencephalographic sleep in schizophrenia: a critical review.  Compr Psychiat. 1990;  31 34-37
    CrossrefPubMedSearch in Google Scholar
  • 16 Kupfer D J, Wyatt R J, Scott J, Snyder F. Sleep disturbance in acute schizophrenic patients.  Am J Psychiat. 1970;  126 1213-1223
    PubMedSearch in Google Scholar
  • 17 Lewis C F, Tandon R, Shipley J E, DeQuardo J R, Jibson M, Taylor S F, Goldman M. Biological predictors of suicidality in schizophrenia.  Acta Psychiat Scand. 1996;  94 416-420
    PubMedSearch in Google Scholar
  • 18 Mason S L, Reynolds G P. Clozapine has sub-micromolar affinity for 5-HT1A receptors in human brain tissue.  Eur J Pharmacol. 1992;  221 397-398
    CrossrefPubMedSearch in Google Scholar
  • 19 Rechtschaffen A, Kales A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Washington, DC: Superintendent of Documents, U.S. Government Printing Office 1968
    Search in Google Scholar
  • 20 Riemann D, Hohagen F, Fleckenstein P, Schredl M, Berger M. The cholinergic REM induction test with RS86 after scopolamine treatment in healthy subjects.  Psychiat Res. 1991;  38 247-260
    CrossrefPubMedSearch in Google Scholar
  • 21 Riemann D, Hohagen F, Krieger S, Gann H, Müller W E, Olbrich R, Wark H J, Bohus M, Low H, Berger M. Cholinergic REM induction test: muscarinic supersensitivity underlies polysomnographic findings in both depression and schizophrenia.  J Psychiat Res. 1994;  28 195-210
    PubMedSearch in Google Scholar
  • 22 Salin-Pascual R J, Herrera-Estrella M, Galicia-Polo L, Laurrabaquio M. Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency.  Biol Psychiat. 1999;  46 141-143.
    PubMedSearch in Google Scholar
  • 23 Sanger T M, Liebermann J A, Tohen M, Grundy S, Beasley C J r, Tollefson G D. Olanzapine versus haloperidol treatment in first-episode psychosis.  Am J Psychiat. 1999;  156 79-87
    PubMedSearch in Google Scholar
  • 24 Schuld A, Kühn M, Haack M, Kraus T, Hinze-Selch D, Lechner C, Pollmächer T. A comparison of the effects of clozapine and olanzapine on the EEG in patients with schizophrenia.  Pharmacopsychiatry. 2000;  33 109-111
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Sharpley A L, Vassallo C M, Cowen P J. Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo.  Biol Psychiat. 2000;  47 468-470
    CrossrefPubMedSearch in Google Scholar
  • 26 Stern M, Fram D, Wyatt R, Grinsponn L, Tursky B. All night sleep studies of acute schizophrenics.  Arch Gen Psychiat. 1969;  20 470-477
    PubMedSearch in Google Scholar
  • 27 Tandon R, Shipley J E, Taylor S, Greden J F, Eiser A, DeQuardo J, Goodson J. Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.  Arch Gen Psychiat. 1992;  49 185-194
    PubMedSearch in Google Scholar
  • 28 Tollefson G D, Beasley C M, Tran P V, Street J S, Krueger J A, Tamura R N, Graffeo K A, Thieme M E. Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective disorders: results of an international collaborative trial.  Am J Psychiat. 1997;  154 457-456
    PubMedSearch in Google Scholar
  • 29 Tollefson G D, Sanger T M. Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol controlled trial with olanzapine.  Am J Psychiat. 1997;  154 466-474
    PubMedSearch in Google Scholar
  • 30 Tollefson G D, Sanger T M, Lu Y, Thieme M E. Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol.  Arch Gen Psychiat. 1998;  55 250-258
    CrossrefPubMedSearch in Google Scholar
  • 31 Virkkunen M, Wahlbeck K, Rissanen A, Naukkarinen H, Franssila-Kallunki A. Decrease of energy expenditure causes weight increase in olanzapine treatment - a case study.  Pharmacopsychiatry. 2002;  35 124-126
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Wetter T C, Lauer C J, Gillich G, Pollmächer T. The electroencephalographic sleep pattern in schizophrenic patients treated with clozapine or classical antipsychotic drugs.  J Psychiat Res. 1996;  30 411-419
    PubMedSearch in Google Scholar

Priv.-Doz. Dr. med. Dipl.-Psych. Matthias J. Müller

Department of Psychiatry

University of Mainz

Untere Zahlbacher Straße 8

D-55131 Mainz

Germany

Phone: +49-6131-17-2920

Fax: +49-6131-17-6690

Email: mjm@mail.psychiatrie.klinik.uni-mainz.de