Sleep in Schizophrenia: Pathology and Treatment

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Key points

  • Insomnia is a hallmark of schizophrenia, and a marked increase in insomnia is a prodromal sign of impending psychosis or clinical relapse.

  • In general, antipsychotic agents (APs) ameliorate this insomnia.

  • However, APs may also induce or exacerbate comorbid sleep disorders such as restless legs syndrome or sleep-disordered breathing.

  • Sleep disorders in schizophrenia should be vigorously treated.

  • A positive clinical outcome may be associated with the normalization of sleep and its restorative

Schizophrenia: a brief overview

Our understanding of schizophrenia continues to advance in a range of diverse disciplines: psychiatry, genetics, neurology, physiology, biochemistry, pharmacology, pathology, and epidemiology. Although the etiology of the disease presents an ongoing challenge, the prevailing model to emerge views schizophrenia as a neurodevelopmental disorder with a lifetime prevalence of 0.7% and a male-to-female incidence ratio of 1.4 worldwide.1

Despite decades of research, there is no laboratory-based

Subjective Assessment

In their subjective assessment of sleep, schizophrenics almost uniformly claim poor sleep quality and significant sleep disruption. Poor sleep quality may include general restlessness and agitation in addition to disturbing hypnagogic hallucinations and nightmares. Schizophrenics may also experience sleep reversals whereby the major sleep period occurs during the day with wakefulness at night. More typically, schizophrenics describe severe insomnia, particularly during episodes of relapse or

Clinical correlates

The relationship between PSG-defined sleep variables and clinical presentation, neurocognitive impairment, and outcome has been reviewed.14 Significant findings are shown in Table 2. Global symptom severity is associated with greater wake time, less SWS or stage N3, and shorter RL. Positive symptoms such as hallucinations and delusions are associated with poor SE, longer SL, shorter RL, increased REM sleep eye movement activity, and increased HFA in the underlying electroencephalogram (EEG). By

Antipsychotic medication

Most patients diagnosed with schizophrenia are treated with one or more of the AP agents shown in Table 3. These APs have differential effects on many neurotransmitter systems including dopamine (DA), serotonin (5-HT), α-adrenergic, cholinergic, and histamine receptors.15 Clinical outcome and the associated side effects on these APs reflect their differential receptor-binding profiles.

The first-generation APs (FGAs) were introduced in the 1950s with the release of chlorpromazine. This agent and

Effects of antipsychotics on sleep

Broadly speaking, AP agents ameliorate the dyssomnias associated with schizophrenia. Table 4 summarizes the results of PSG studies that evaluated AP effects on sleep.9, 15 In most instances, these studies had certain limitations. Double-blind placebo-controlled studies were rare, and many were cross-sectional comparisons that failed to use subjects as their own controls. Quetiapine and ziprasidone have been evaluated only in nonpsychiatric controls and, as yet, PSG studies of the newer SGAs

Insomnia

Despite treatment with AP agents, it is not uncommon for schizophrenics to complain of unresolved insomnia. In fact, rates of residual insomnia in AP-treated schizophrenics range from 16% to 30%.16 Often this insomnia can be attributed to inadequate or undertreated hyperarousal or to sleep-related movement disorders.

As reviewed earlier, insomnia is the most consistently reported dyssomnia associated with schizophrenia. Long SL and poor SE are emblematic of the hyperarousal and psychotic turmoil

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    Disclosure: This was not an industry-supported study. There is no financial conflict of interest.

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