Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics.
TL;DR: 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.
Abstract: 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.
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University of Freiburg1, University of Bergen2, Northumbria University3, University of Oxford4, Stavanger University Hospital5, Karolinska Institutet6, University of Copenhagen7, Paris Descartes University8, University of Parma9, National Institutes of Health10, University of Antwerp11, University of Bucharest12, Frederiksberg Hospital13
TL;DR: In this article, a European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia.
Abstract: This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).
1,076 citations
TL;DR: It is proposed that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms.
Abstract: Sleep and circadian rhythm disruption are frequently observed in patients with psychiatric disorders and neurodegenerative disease. The abnormal sleep that is experienced by these patients is largely assumed to be the product of medication or some other influence that is not well defined. However, normal brain function and the generation of sleep are linked by common neurotransmitter systems and regulatory pathways. Disruption of sleep alters sleep-wake timing, destabilizes physiology and promotes a range of pathologies (from cognitive to metabolic defects) that are rarely considered to be associated with abnormal sleep. We propose that brain disorders and abnormal sleep have a common mechanistic origin and that many co-morbid pathologies that are found in brain disease arise from a destabilization of sleep mechanisms. The stabilization of sleep may be a means by which to reduce the symptoms of--and permit early intervention of--psychiatric and neurodegenerative disease.
864 citations
13 Dec 2017
TL;DR: This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia.
810 citations
Cites background from "Sleep disturbances in patients with..."
...Monti and Monti (2004; Monti et al., 2017) and Cohrs (2008) concluded that sedating antipsychotics increase total sleep time and the amount of slow-wave sleep in patients with schizophrenia....
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TL;DR: An overview of existing literature on the relation between poor sleep and aggression, irritability, and hostility is given and individual variation within these neurobiological systems may be responsible for amplified aggressive responses induced by sleep loss in certain individuals.
323 citations
TL;DR: The question is: can the early and adequate treatment of insomnia prevent depression, and current understanding about sleep regulatory mechanisms with knowledge about changes in physiology due to depression are linked.
294 citations
Cites background from "Sleep disturbances in patients with..."
...With respect to AP even less evidence is available—studies are available investigating the effects of AP on sleep in schizophrenia [154] and in insomnia [155, 156]....
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References
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TL;DR: A quite consistent level of depressive symptomatology is therefore present in subpopulations of delusional and schizophrenic subjects other than in affective subjects, and some symptoms that are common across all major psychoses and symptoms that is more specific to each group are identified.
Abstract: The aim of this study was to investigate depressive symptomatology across distinct major psychiatric disorders. A total of 1351 subjects affected by major depressive disorder (MDD = 389), bipolar disorder (BP = 511), delusional disorder (DD = 93) and schizophrenia (SKZ = 358) were included in our study. Subjects were assessed using the Operational Criteria for Psychotic Illness checklist (OPCRIT). The most frequently represented depressive symptoms in MDD were Loss of energy/tiredness, Loss of pleasure, Poor concentration, and Sleep disorders. Compared with MDD, BP had higher occurrences of Agitated activity, Excessive sleep, and Increased appetite and/or Weight gain, as well as lower Loss of pleasure. In our sample, 32.3% and 26.8% of DD and SKZ, respectively, had quite consistent depressive symptomatology, with at least four or more depressive symptoms. The most common depressive symptoms were Sleep disorders, Poor concentration and Loss of energy/Tiredness, followed by Psychomotor symptoms in SKZ only. Excessive self-reproach, Suicidal ideation, and Appetite and/or Weight changes were more specific to mood disorders. Finally, compared with SKZ, DD suffered from more depressive symptoms and had more severe depressive symptomatology. A quite consistent level of depressive symptomatology is therefore present in subpopulations of delusional and schizophrenic subjects other than in affective subjects. We identified some symptoms that are common across all major psychoses and symptoms that are more specific to each group.
58 citations
TL;DR: Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy and were maintained through at least 7 weeks of therapy, however, clozAPine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients.
Abstract: There have been limited reports on the effect of the atypical anti-psychotic agent clozapine on sleep measures and hormone secretion. The goal of this study was to determine the type, rate, and extent of changes in sleep measures and nighttime secretion of growth hormone (GH) and cortisol during clozapine treatment. Five schizophrenic patients (age: 32.4+/-7.4) and five age- and sex-matched normal subjects (age: 33.0+/-5.1) underwent nocturnal polysomnography (NPSG) before clozapine therapy (S1), and during early and late clozapine therapy (S2 and S3). Serum GH and cortisol levels were monitored during each NPSG. NPSG findings showed that the mean total sleep time, sleep efficiency, and duration of awakening were increased at S2, and maintained until S3. The mean amounts of stage 2 sleep at S2 and S3 increased significantly compared with that of S1. In unmedicated schizophrenic patients, the mean plasma GH level in rapid eye movement sleep was lower than during the waking stage, and the mean level of plasma cortisol was higher during the waking stage. Plasma cortisol levels did not differ between control subjects and patients at any time, but clozapine treatment decreased plasma cortisol levels at S2 compared with S1 and S3. Plasma GH levels were unchanged by clozapine treatment. Clozapine improved sleep continuity and increased stage 2 sleep time from the beginning of therapy. These effects were maintained through at least 7 weeks of therapy. However, clozapine did not affect the relationship of plasma GH and cortisol levels with sleep stages in schizophrenic patients.
56 citations
TL;DR: The effects of chlorpromazine and imipramine on the human nocturnal sleep EEG were investigated and the difference in the mode of action of drugs was observed.
Abstract: Summary
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The effects of chlorpromazine and imipramine on the human nocturnal sleep EEG were investigated and the difference in the mode of action of drugs was observed.
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Administration of chlorpromazine did not markedly modify the EEG activity, but made the frequency of spindle waves somewhat lower.
Imipramine caused the accentuation of fast waves in the drowsy state ana increased the frequency of spindle waves.
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Administration of chlorpromazinc increased the amount of the phase of low voltage θ-waves with the occurrene of rapid eye ball movements, in the form of either prolonging the duration of one phase or increasing the incidence of this phase throughout the night. This tendency was observed in 5 of the 7 cases using the dosages of 50 mg.
Administration of chlorpromazine also stabilized the phase of spindle and δ waves lessening the incidence of body movement throughout the night.
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Imipramine, contrary to chlorpromazine, decreased the amount of the phase of low voltage θ-waves accompanied by rapid eye ball movements and replaced this phase with spindle and δ-wave stage accompanied by abundant body movements. This effect was observed in all 6 of the cases with a dosage of 50 mg.
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Concerning the phenothiazine derivatives other than chlorpromazine, per-phenazine produced changes similar to chlorpromazine, but levomepromazine proved opposite to chlorpromazine, that is, it produced changes resembling to those of imipramine.
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As for the durgs similar to imipramine in clinical action, amitriptylin and desmethlimipramine elicited similar changes on the sleep EEG pattern to imipramine. One of the MAO-inhibitors, nialamide also showed the same tendency.
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Discussions were made on the clinical action of these drugs. The effects of other drugs, LSD-25, alcohol, and trihexyphenidyl were referred for comparison.
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These findings were also discussed in the light of the data obtained from animal experiments.
56 citations
TL;DR: Findings suggest an association between REM sleep abnormalities and suicidal behavior, perhaps related to alteration in serotonergic function.
Abstract: The purpose of the study was to determine whether polysomnographic rapid eye movement (REM) sleep parameters distinguish between psychotic patients with and without a history of suicidal behavior. We examined both hand-scored and automated measures of rapid eye movement (REM) sleep in psychotic patients with and without a history of suicidal ideation or attempts. Patients with suicidal behavior had significantly increased REM activity and time both in the whole night data and in the first REM period. These findings suggest an association between REM sleep abnormalities and suicidal behavior, perhaps related to alteration in serotonergic function.
56 citations
TL;DR: Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep).
Abstract: Objective Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. Method The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. Results Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. Conclusion Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.
55 citations