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 measuresof 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.

Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics.

The Leeds Sleep Evaluation Questionnaire comprises ten self-rating 100-mm-line analogue questions concerned with aspects of sleep and early morning behaviour. The questionnaire has been used to monitor subjectively perceived changes in sleep during psychopharmacological investigations involving a variety of psychoactive agents, including sedative-hypnotics, antidepressants, anxiolytics, CNS stimulants, and antihistamines. Dose-related improvements in the self-reported ratings of getting to sleep and perceived quality of sleep were generally associated with reductions in the self-reported levels of alertness and behavioural integrity the morning following the nocturnal administration of sedative hypnotic and anti-anxiety agents. Psychostimulants on the other hand, impaired subjective ratings of sleep and produced increases in early morning assessments of alertness. Certain antidepressant and antihistaminic agents produced effects similar to the sedative-hypnotics, while others did not affect self-reported aspects of sleep and early morning behaviour.

/pdf/the-leeds-sleep-evaluation-questionnaire-in-kqx2wpcsjy.pdf

The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review.

Polysomnographic abnormalities in schizophrenia are not well characterized and their associations with schizophrenic symptomatology have not been adequately assessed. To address these issues, we recorded electroencephalographic sleep in 20 drug-naive schizophrenics, 20 drug-free but previously medicated schizophrenics, and 15 normal controls. Drug-naive and previously medicated patients had significantly greater impairment of sleep continuity and shorter rapid eye movement latency when compared with controls. In the previously medicated group, findings were significantly influenced by duration of drug-free status. Rapid eye movement latency was inversely correlated with the severity of negative symptoms (r = -.52) but was unrelated to depressive symptoms. Slow-wave sleep did not differ between schizophrenic patients and normal controls and was unrelated to any clinical parameter. Mechanisms underlying the observed associations between rapid eye movement sleep abnormalities and negative symptoms in the acute phase of schizophrenic illness need to be explored.

Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.

The dopamine D1 receptor is involved in the regulation of REM sleep in the rat.

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/29068/0000102.pdf;sequence=1

Effect of neuroleptic treatment on polysomnographic measures in schizophrenia.

1 Mesoridazine, a phenothiazine of short half-life, and potentially useful as an hypnotic, has here been investigated using volunteers of late middle age. 2 The electrophsiological recording of all-night sleep was studied in seven subjects for a 7-week period during which ther received mesoridazine (10 mg nightly) for 3 weeks. The drug reduced the frequency of transitions into wakefulness and stage 1 (drowsiness) and reduced the time spent in stage 1; there was a withdrawal rebound. Mesoridazine increased REM sleep above baseline levels and a rebound fall below baseline occurred on withdrawal. The drug did not alter the amount of stage 3 + 4 slow wave sleep. 3 Subjective self-ratings were assessed in a 6-week study of sixteen subjects. Sleep quality improved on mesoridazine (10 mg nightly) but there was diminution of zest and freshness 20 min after rising. Daytime concentration and anxiety were rated as not affected either by administration or withdrawal.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.1976.tb00583.x

I Carruthers-Jones

Papers

Mesoridazine and human sleep.