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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41 citations
TL;DR: Sleep latency and awake time were significantly decreased on chlorpromazine while stage II, delta sleep, delta%, nonrapid eye movement (NREM) sleep, REM activity, REM latency, and REM density were significantly increased.
Abstract: The sleep of 13 chronic male schizophrenics was studied during a one-month trial of chlorpromazine and compared with one-month placebo periods. Electroencephalographic recordings were made only after the patients had been on chlorpromazine hydrochloride or a placebo for at least three weeks. Sleep latency and awake time were significantly decreased on chlorpromazine while stage II, delta sleep, delta%, nonrapid eye movement (NREM) sleep, REM activity, REM latency, and REM density were significantly increased. There were no significant changes in REM time, REM%, stage II%, and NREM%.
41 citations
TL;DR: Efficacy of valproate in treating RLS has been shown, and it is therefore less likely to be an etiological factor in this patient’s presentation, while clozapine use did not result in reemergence of symptoms with clozAPine rechallenge.
Abstract: To the Editors: Restless legs syndrome (RLS) is a neurological disorder characterized by irresistible movements and dysesthetic sensations in the legs. Its prevalence in general population epidemiological studies is 5% to 10%. Drug-induced RLS, although now a recognized entity, remains an underdiagnosed etiology of secondary RLS. Selective serotonin reuptake inhibitors have long been known to exacerbate RLS, and it has anecdotally been described with atypical antipsychotics. However, there are no reports of clozapine-induced RLS in literature. A case of RLS associated with clozapine is described. The underlying pathophysiological mechanism of this presentation is discussed. Mr A, a 26-year-old man, was diagnosed with bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) with a 6-year duration. During one of the manic episodes, he developed severe extrapyramidal symptoms characterized by tremors, bradykinesia, and sialorrhea while on haloperidol 20 mg/d and valproate 1400 mg/d. Subsequently, haloperidol was replaced by clozapine 25 mg/d, which was increased to 50 mg/d over the next 2 days, whereas valproate was continued at the same dose. On the third day of treatment with clozapine (at 50 mg/d), he started experiencing unpleasant sensations in his calves and burning sensation over his feet. These occurred only when he lay in bed at night and would be relieved by moving the legs or walking but would recur on lying in bed. He had initial and middle insomnia. Mr A denied having these symptoms during the daytime. Considering that this may be akathisia, lorazepam (2 mg) was added at bedtime. However, he continued to exhibit the same symptoms, but only at night. Two days later, clozapine was stopped; and that night, Mr A did not experience any uncomfortable sensations or movements of his legs. A week later, the patient agreed to a retrial of clozapine manufactured by a different pharmaceutical company. However, he again developed the same symptoms at night. Subsequently, clozapine was replaced by olanzapine titrated up to 20 mg/d without reemergence of the above symptoms. The dose of valproate remained unchanged throughout the course of treatment. Family history revealed that the patient’s father had evidence to suggest idiopathic RLS. The patient’s neurological examination was unremarkable. Laboratory investigations including serum iron, ferritin, glucose, thyroid-stimulating hormone, and renal function tests were within normal limits. Because of the transient nature and drug-related origin of the abnormal movement, the patient did not consent to polysomnography. This patient met the diagnostic criteria for RLS. Unfortunately, polysomnography data were not available to diagnose or exclude comorbid periodic leg movements in sleep. Akathisia was ruled out on the basis of the presence of dysesthesias in the legs rather than internal restlessness, worsening of symptoms at night, accompanying sleep disturbance, and positive family history. A PubMed search done on June 8, 2006, did not reveal any case of RLS associated with clozapine. Other atypical antipsychotics implicated in RLS include olanzapine, risperidone, and quetiapine. Idiopathic RLS is unlikely because of the lack of history of RLS, the close temporal relationship between clozapine use and RLS, and the reemergence of symptoms with clozapine rechallenge. Efficacy of valproate in treating RLS has been shown, and it is therefore less likely to be an etiological factor in this patient’s presentation. In contrast to our report, clozapine use did not result in reemergence of symptoms in a patient who had developed RLS because of olanzapine. This raises some interesting questions regarding our current understanding of the pathophysiology of RLS. One of the pathophysiological mechanisms of RLS is dopaminergic dysfunction as evidenced by dopamine agonists being the first line of treatment of RLS and dopamine antagonists such as antipsychotics inducing it. If dopaminergic hypofunction is the promulgated mechanism underlying RLS, then clozapine and quetiapine, with lower D2 receptor occupancy compared with other atypical antipsychotics such as risperidone and olanzapine, are less likely to induce RLS as suggested by some investigators. However, this report and the previous report of quetiapineinduced RLS do not support the hypodopaminergic hypothesis for RLS, especially when our patient did not develop RLS with haloperidol and olanzapine, which are more potent D2 antagonists. Thus, more research is needed to elucidate the underlying mechanism of druginduced RLS. In addition, greater awareness among clinicians of the potential association of atypical antipsychotics with RLS and its differentiation from akathisia is encouraged.
40 citations
TL;DR: The association between decreases brain anabolic processes (reflected by decreased PME) and decreased SWS may be related either to processes of accelerated aging or to developmentally mediated alterations in cortical synaptic pruning, postulated to underlie the pathophysiology of functional psychoses.
Abstract: Deficits in slow wave sleep (SWS) are consistently seen in schizophrenia and related psychotic disorders. However, the pathophysiological significance of this finding is uncertain. In 19 patients with psychotic illness, sleep and 31 P-magnetic resonance spectroscopy (MRS) studies were carried out before the patients began medication treatment. Polysomnographic studies were carried out on 2–3 consecutive nights. MRS studies were performed with a surface coil and a depth-resolved pulse sequence focusing on the dorsal prefrontal cortex. Phosphomonoesters were correlated with visually scored delta and Stage 4 sleep, as well as with automated delta wave counts. An inverse relation was also seen between negative symptom scores and SWS. The association between decreased brain anabolic processes (reflected by decreased PME) and decreased SWS may be related either to processes of accelerated aging or to developmentally mediated alterations in cortical synaptic pruning, postulated to underlie the pathophysiology of functional psychoses.
40 citations
TL;DR: It is demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotics, suggesting that the marked potency of serotonin-2 receptor blockade in atypicals antippsychotic drugs may be involved in the mechanism of this improvement.
Abstract: Objective: To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. Method: Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive I of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). Results: Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. Conclusion: These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.
40 citations