Sleep Disturbances in Patients with Schizophrenia Impact and Effect of Antipsychotics

Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Disturbed sleep can be found in 30-80% of schizophrenic patients, depending on the degree of psychotic symptomatology. Measured by polysomnography, reduced sleep efficiency and total sleep time, as well as increased sleep latency, are found in most patients with schizophrenia and appear to be an important part of the pathophysiology of this disorder. Some studies also reported alterations of stage 2 sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep variables, i.e. reduced REM latency and REM density. A number of sleep parameters, such as the amount of SWS and the REM latency, are significantly correlated to clinical variables, including severity of illness, positive symptoms, negative symptoms, outcome, neurocognitive impairment and brain structure. Concerning specific sleep disorders, there is some evidence that schizophrenic patients carry a higher risk of experiencing a sleep-related breathing disorder, especially those demonstrating the known risk factors, including being overweight but also long-term use of antipsychotics. However, it is still unclear whether periodic leg movements in sleep or restless legs syndrome (RLS) are found with a higher or lower prevalence in schizophrenic patients than in healthy controls. There are no consistent effects of first-generation antipsychotics on measures of sleep continuity and sleep structure, including the percentage of sleep stages or sleep and REM latency in healthy controls. In contrast to first-generation antipsychotics, the studied atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone, ziprasidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity, with an increase in either total sleep time (TST) or sleep efficiency, and individually varying effects on other sleep parameters, such as an increase in REM latency observed for olanzapine, quetiapine and ziprasidone, and an increase in SWS documented for olanzapine and ziprasidone in healthy subjects. The treatment of schizophrenic patients with first-generation antipsychotics is consistently associated with an increase in TST and sleep efficiency, and mostly an increase in REM latency, whereas the influence on specific sleep stages is more variable. On the other hand, withdrawal of such treatment is followed by a change in sleep structure mainly in the opposite direction, indicating a deterioration of sleep quality. On the background of the rather inconsistent effects of first-generation antipsychotics observed in healthy subjects, it appears possible that the high-potency drugs exert their effects on sleep in schizophrenic patients, for the most part, in an indirect way by suppressing stressful psychotic symptomatology. In contrast, the available data concerning second-generation antipsychotics (clozapine, olanzapine, risperidone and paliperidone) demonstrate a relatively consistent effect on measures of sleep continuity in patients and healthy subjects, with an increase in TST and sleep efficiency or a decrease in wakefulness. Additionally, clozapine and olanzapine demonstrate comparable influences on other sleep variables, such as SWS or REM density, in controls and schizophrenic patients. Possibly, the effects of second-generation antipsychotics observed on sleep in healthy subjects and schizophrenic patients might involve the action of these drugs on symptomatology, such as depression, cognitive impairment, and negative and positive symptoms. Specific sleep disorders, such as RLS, sleep-related breathing disorders, night-eating syndrome, somnambulism and rhythm disorders have been described as possible adverse effects of antipsychotics and should be considered in the differential diagnosis of disturbed or unrestful sleep in this population. Difficulties initiating or maintaining sleep are frequently encountered in patients with schizophrenia. Sleep disturbance is often part of the prodromal phase before the development of manifest psychotic symptomatology, it may persist during the course of the disorder and appears to be involved in the pathophysiology of a variety of clinical aspects of this illness. Therefore, the influence of antipsychotic medication on sleep in general and specifically on sleep in patients. with schizophrenia is of special interest. This article describes the basic characteristics of sleep regulation, subjective and polysomnographic measures of sleep disturbance in schizophrenic patients, and the available information on the relationship between sleep and different areas of patients' impairment, including severity of illness, positive and negative symptoms, outcome, and cognitive deficits. Based on this information, we present the available knowledge about the effects of first- and second-generation antipsychotics on sleep in healthy subjects and in patients with schizophrenia. Additionally, specific sleep disorders and their relevance to the care of schizophrenic patients are described. A computer-based MEDLINE search was conducted of available articles published between January 1966 and October 2007 using the following key terms: schizophren* and sleep, antipsychot* or neurolept* and sleep, and (amisulprid*, or benperidol*, or bromperidol*, or chlorpromazine*, or chlorprothix*, or clopenthixol*, or clozapine, or flupentixol, or fluphenazin*, or fluspirilen*, or haloperidol* or levomepromazin*, or melperon*, or olanzapin*, or perazin*, or perphenazin*, or pimozid*, or pipamperon*, or promazin*, or prothipendyl, or quetiapin*, or risperidon*, or sertindol*, or sulpirid*, or thioridazin*, or trifluperazin*, or trifluperidol*, or trifluperazin*, or zotepin, or ziprasidone, or zuclopenthixol) and (sleep EEG or polysomnogra* or [sleep and EEG]). The references of published articles identified from the search strategy were also examined for any additional references. The articles were limited to studies conducted with human participants.