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.

Drug effects on REM sleep and on endogenous depression

The relationship of alpha and delta EEG frequencies to pain and mood in ‘fibrositis’ patients treated with chlorpromazine and l-tryptophan ☆

In two separate experiments, sleep patterns of 17 young male adults were examined following single and repeated doses (0.9 g/kg body weight) of alcohol. A third study of 10 additional Ss measured the rate of elimination of alcohol from blood during sleep and waking. With a single dose of alcohol, onset of sleep was brisk, the latency of SW sleep (stages 3+4) was reduced and the first episode of stage REM was shortened. These transient alterations were accompanied by loss of high-frequency beta rhythms in the EEG and a gain in abundance and synchrony of activity in the alpha-rhythm range.

Alcohol and sleep in young adults.

https://www.neurologic.theclinics.com/article/S0733-8619(05)70287-5/pdf

Effects of drugs on sleep

Sleep patterns of 14 male Ss were examined following a single oral dose (200 mg) of the barbiturate secobarbital. Compared to baseline, medication caused definite changes in the amount and distribution of the EEG stages of sleep. With the drug, a decrease in percent stage REM and an increase in percent stage 2 were accompanied by fewer body movements and a trend toward less waking. A more striking effect was the drug-induced redistribution of EEG stages with slow-wave sleep potentiated during the first half of the night but virtually eliminated during the last half. Stage REM, on the other hand, was inhibited in the first half but returned to baseline levels in the last half of the night. Recent evidence suggests that such effects could result from modulation of brain levels of the monoamines. Within the stages of sleep the amount of fast EEG activity was increased by the drug, with a tendency toward desynchrony. Pre-central beta activity became especially prominent in stages REM and 2 (low-voltage phases), and this change was associated with inhibition of such phasic events as eye movements during REM sleep, sigma spindles during stage 2 and spontaneous electrodermal responses in slow-wave sleep. Thus, it appears that secobarbital potentiates tonic and suppresses phasic phenomena during sleep. A possible interpretation of these results is that secobarbital enhances electrical activity in forebrain structures (Routtenberg's arousal system II) while inhibiting the reticular activating system (arousal system I) causing a reduction of phasic variability in all stages of sleep.

Secobarbital and nocturnal physiological patterns.

The aim of this study was to examine human physiological sleep profiles, including the amount and distribution of electroenoephalographic (EEG) stages of sleep, variations in specific frequency bands in the EEG spectrum and certain phasic phenomena such as movement arousals, sigma spindles and rapid eye movements, following oral administration of a moderate dose (150 mg) of chlorpromazine (CPZ) to 12 young male volunteers. At this dose level the drug had few systematic effects on sleep, although it did reduce the latency of onset of stage REM and the number of movement arousals, while increasing the amount of slow-wave (SW) sleep. These effects persisted during the post-medication recovery night, but at no time was there any systematic change in the total amount or percent of REM sleep, the duration of the REM-to-REM cycle, the average length of REM episodes or the density of rapid eye movements during stage REM. Frequency analysis of EEG revealed that CPZ produced a trend toward increased fast (beta) activity recorded from pre-central placements during stage REM, and reduced density of sigma spindles in stage 2 sleep. Thus, for the most part, a single moderate dose of CPZ left the tonic, phasic and sequential properties of the sleep cycle unaltered. These results confirm previous investigations showing that for small to moderate clinical doses, CPZ invariably enhances SW sleep and reduces the frequency of movement arousals. On the other hand, the effect of the drug on stage REM apparently depends on dose. Small doses potentiate REM sleep or accelerate its onset, whereas larger doses either reduce stage REM or leave it unaffected. Several authors have pointed out that most hypnotic agents cause substantial alterations of the sleep profile, and that their withdrawal can cause profound disruption of sleep and marked clinical disturbance. It also has been suggested that there exists a relation between drug dependency and the degree of initial REM suppression caused by a drug. The finding confirmed by the present study that clinical doses of CPZ cause mild sedation, and enhanced SW sleep without any significant modification of REM, sleep, indicates that CPZ has features which may recommend it as a standard hypnotic.

Lawrence C. Cowden

Papers

Secobarbital and nocturnal physiological patterns.

Chlorpromazine and human sleep