Elsevier

Sleep Medicine Reviews

Volume 8, Issue 2, April 2004, Pages 133-148
Sleep Medicine Reviews

Clinical Review
Sleep in schizophrenia patients and the effects of antipsychotic drugs

https://doi.org/10.1016/S1087-0792(02)00158-2Get rights and content

Abstract

Insomnia is a common feature in schizophrenia. However, it seldom is the predominant complaint. Nevertheless, severe insomnia is often seen during exacerbations of schizophrenia, and may actually precede the appearance of other symptoms of relapse. The sleep disturbances of either never-medicated or previously treated schizophrenia patients are characterized by a sleep-onset and maintenance insomnia. In addition, stage 4 sleep, slow wave sleep (stages 3 and 4), non-REM (NREM) sleep in minutes and REM latency are decreased. The atypical antipsychotics olanzapine, risperidone, and clozapine significantly increase total sleep time and stage 2 sleep. Moreover, olanzapine and risperidone enhance slow wave sleep. On the other hand, the typical antipsychotics haloperidol, thiothixene, and flupentixol significantly reduce stage 2 sleep latency and increase sleep efficiency.

Future research should address: (1) the sleep patterns in subtypes of schizophrenia patients; (2) the role of neurotransmitters other than dopamine in the disruption of sleep in schizophrenia; (3) the functional alterations in CNS areas related to the pathophysiology of schizophrenia during NREM sleep and REM sleep (brain imaging studies); (4) the short-term, intermediate-term, and long-term effects of atypical antisychotics on sleep variables.

Introduction

According to the DSM-IV1 the essential features of schizophrenia are “a mixture of characteristic positive and negative signs and symptoms that have been present during 1-month period with some signs of the disorder persisting for at least 6 months”. Insomnia is a common feature of schizophrenia. To be considered as a symptom related to schizophrenia, the sleep disturbance must last for at least 1 month and be associated with daytime fatigue or impaired daytime functioning.1

The onset of schizophrenia typically occurs in early adulthood between 15 and 35 years of age.2 The course of schizophrenia is variable, with some patients displaying exacerbations and remissions, whereas others remain chronically ill. The subtypes of schizophrenia are defined by the predominant symptomatology at the time of evaluation, and include the catatonic, paranoid, and undifferentiated type.

Structural abnormalities in the brain have consistently been found in schizophrenia patients. These include enlargement of the ventricular system and sulci in the cortex. In addition, structural imaging techniques have provided evidence of decreased temporal and hippocampal size, increased size of the basal ganglia and decreased cerebral size in a substantial number of patients.1

Section snippets

Sleep disturbances associated with schizophrenia

Although the sleep disturbances in schizophrenia could be sufficiently severe to warrant independent clinical attention, they seldom are the predominant complaint. Nevertheless, severe insomnia is often seen during exacerbations of schizophrenia, and may actually precede the appearance of other symptoms of relapse.3 Less frequently, severe sleep disruption may complicate schizophrenia to the degree that patients can become suicidal.4

Following the development of polysomnography, sleep

Never-medicated schizophrenia patients

A total of 75 patients and 61 normal controls were included in five studies. The patients included in the studies by Ganguli et al.,6 Tandon et al.,7 and Lauer et al.8 had mean ages of 21.5, 26.8, and 32.7 years, respectively. On the other hand, the patients studied by Jus et al.9 had a mean age of 70.8 years. The latter is of special concern because sleep quality and maintenance decline in elderly subjects irrespective of the concurrent psychiatric disorder. In four studies sleep was assessed

Schizophrenia patients previously treated with neuroleptics

(1) Studies that included a control group. A total of 200 young patients aged 18.0–35.0 (mean 29.9) years and 190 normal controls aged 20.0–31.3 (mean 28.3) years were included in 13 studies. Keshavan et al.13 included in their study 19 patients who had received no neuroleptic medications previously and 11 patients who had a mean medication-free period of 2 years. As a whole patients had not been taking neuroleptics prior to the study for periods ranging from 1–2 days to 1–2 years. In two

Delta sleep and negative symptoms of schizophrenia

Most polysomnographic studies have detected a reduction of visually scored stage 4 sleep and slow wave sleep (stages 3 and 4) in schizophrenia patients. In addition, the duration of visually scored stage 4 sleep or slow wave sleep has been shown to be inversely correlated with the severity of negative symptoms.6., 33. Automated delta sleep measures revealed that total and average delta wave counts were also inversely associated with negative symptoms.39 Kajimura et al.40 have investigated the

Consistency and shortcomings

It can be concluded that studies of sleep in schizophrenia have failed to generate consistent findings. This is more evident in the early studies in which the diagnostic criteria were not specified or non-standardized diagnostic procedures were used.9., 19., 20., 21., 22., 23., 29., 30., 31. In addition, some sleep studies employed scoring methods that are no longer used.19., 20., 21., 22., 23., 29.

Other methodological shortcomings include: small number of subjects,6., 14., 23., 24., 29., 30.,

What are the mechanisms involved in the disruption of sleep in schizophrenia patients?

The dopamine (DA) hypothesis of schizophrenia formulated in the 1960s states that the symptoms of schizophrenia depend upon the overactivity of the dopaminergic system.42 The latter would be related to an increased density of DA D2 receptors. Nevertheless, recent postmortem and in vivo imaging (PET) studies indicate that about 30% of patients show striatal D2 receptor densities that do not differ significantly from matched control subjects.43 Differences remain significant irrespective of

Effects of atypical and typical antipsychotics on polysomnographic measures of sleep

The difficulties inherent in sleep studies of schizophrenia patients are well known. Considering that the availability of EEG sleep data on the effects of antipsychotic drugs in schizophrenia is sparse, we also included studies in which these compounds were administered to normal subjects. Our analysis was limited to the effects on sleep variables of the atypical antipsychotics olanzapine, risperidone, and clozapine, and the typical antipsychotics haloperidol, thiothixene, and flupentixol.

With

What are the mechanisms involved in the effects of antipsychotic drugs on sleep?

Typical and atypical antipsychotic drugs bind to a wide variety of CNS receptors. They produce their effects by blocking dopamine (D1, D2, D3, D4), serotonin (5-HT2A, 5-HT2C, 5-HT6, 5-HT7), α-adrenergic (α1, α2), histamine (HA) (H1), and acetylcholine (muscarinic) receptors. Irrespective of their chemical structure antipsychotics show intermediate (clozapine) to high (haloperidol, flupentixol, thiothixene, olanzapine, risperidone) affinity for the D2 receptor. In addition, clozapine and

References (74)

  • G.K. Thaker et al.

    Sleep polygraphy in schizophrenia: methodological issues

    Biol Psychiatry

    (1990)
  • S.F. Taylor et al.

    Sleep onset REM periods in schizophrenic patients

    Biol Psychiatry

    (1991)
  • E.A. Nofzinger et al.

    Electroencephalographic sleep in clinically stable schizophrenic patients: two-weeks versus six-weeks neuroleptic free

    Biol Psychiatry

    (1993)
  • V.P. Zarcone et al.

    BPRS symptom factors and sleep variables in schizophrenia

    Psychiatry Res

    (1997)
  • M.S. Keshavan et al.

    Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders

    J Psychiat Res

    (1995)
  • N. Kajimura et al.

    Relationship between delta activity during all-night sleep and negative symptoms in schizophrenia: a preliminary study

    Biol Psychiatry

    (1996)
  • J.M. Monti et al.

    Effects of the dopamine D-2 receptor agonist, quinpirole on sleep and wakefulness in the rat

    Eur J Pharmacol

    (1989)
  • A.L. Sharpley et al.

    Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT2C receptors in vivo

    Biol Psychiatry

    (2000)
  • P.M.J. Haffmans et al.

    The effect of risperidone versus haloperidol on sleep patterns of schizophrenic patients: results of a double-blind, randomised pilot trial

    Eur Neuropsychopharm

    (2001)
  • S.F. Taylor et al.

    Effect of neuroleptic treatment on polysomnographic measures in schizophrenia

    Biol Psychiatry

    (1991)
  • T.C. Wetter et al.

    The electroencephalographic sleep pattern in schizophrenic patients treated with clozapine or classical antipsychotic drugs

    J psychiat Res

    (1996)
  • R.J. Salin-Pascual et al.

    Olanzapine acute administration in schizophrenic patients increases delta sleep and sleep efficiency

    Biol Psychiatry

    (1999)
  • H. Yamashita et al.

    Effect of risperidone on sleep in schizophrenia: a comparison with haloperidol

    Psychiatry Res

    (2002)
  • J.M. Monti

    Disturbances of sleep and wakefulness associated with the use of antihypertensive agents

    Life Sci

    (1987)
  • C. Idzikowski et al.

    5-Hydroxytryptamine-2-antagonist increases human slow wave sleep

    Brain Res

    (1986)
  • Y. Katsuda et al.

    meta-Chlorophenylpiperazine decreased slow wave sleep in humans

    Biol Psychiatry

    (1993)
  • A.L. Sharpley et al.

    Slow wave sleep in humans: role of 5-HT2A and 5-HT2C receptors

    Neuropharmacology

    (1994)
  • D. Hinze-Selch et al.

    Effects of clozapine on sleep: a longitudinal study

    Biol Psychiatry

    (1997)
  • Diagnostic and statistical manual of mental disorders

    (1994)
  • A. Jablensky et al.

    Schizophrenia: manifestations, incidence and course in different cultures. A World Health Organization ten-country study

    Psychol Med Monogr Suppl

    (1992)
  • D.P. Van Kammen et al.

    CSF MHPG sleep and psychosis in schizophrenia

    Clin Neuropharmacol

    (1986)
  • International classification of sleep disorders, revised: diagnostic and coding manual

    (1997)
  • M.A. Carskadon et al.

    Normal human sleep: an overview

  • R. Ganguli et al.

    Electroencephalographic sleep in young, never-medicated schizophrenics

    Arch Gen Psychiatry

    (1987)
  • R. Tandon et al.

    Electroencephalographic sleep abnormalities in schizophrenia

    Arch Gen Psychiatry

    (1992)
  • K. Jus et al.

    Sleep EEG studies in untreated, long-term schizophrenic patients

    Arch Gen Psychiatry

    (1973)
  • A. Rechtschaffen et al.

    A manual of standardized terminology, techniques and scoring system for sleep stages in human subjects

    (1968)
  • Cited by (193)

    View all citing articles on Scopus
    View full text