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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TL;DR: It is argued that an understanding of the mechanistic overlap between SCRD and schizophrenia will ultimately lead to novel treatment approaches, which will not only ameliorate SCRD in schizophrenia patients, but also will improve their broader health problems and overall quality of life.
Abstract: Sleep and circadian rhythm disruption (SCRD) and schizophrenia are often co-morbid. Here, we propose that the co-morbidity of these disorders stems from the involvement of common brain mechanisms. We summarise recent clinical evidence that supports this hypothesis, including the observation that the treatment of SCRD leads to improvements in both the sleep quality and psychiatric symptoms of schizophrenia patients. Moreover, many SCRD-associated pathologies, such as impaired cognitive performance, are routinely observed in schizophrenia. We suggest that these associations can be explored at a mechanistic level by using animal models. Specifically, we predict that SCRD should be observed in schizophrenia-relevant mouse models. There is a rapidly accumulating body of evidence which supports this prediction, as summarised in this review. In light of these emerging data, we highlight other models which warrant investigation, and address the potential challenges associated with modelling schizophrenia and SCRD in rodents. Our view is that an understanding of the mechanistic overlap between SCRD and schizophrenia will ultimately lead to novel treatment approaches, which will not only ameliorate SCRD in schizophrenia patients, but also will improve their broader health problems and overall quality of life.
99 citations
Cites background from "Sleep disturbances in patients with..."
...Crucially, patients with SCRD score badly on many quality-of-life clinical sub- scales, highlighting the human cost of SCRD in schizo- phrenia (Cohrs 2008; Goldman et al. 1996; Hofstetter et al. 2005)....
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...More specifically, schizophrenia patients treated with typical antipsychotics show an increase in their sleep efficiency and total sleep time (Cohrs 2008)....
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...Recent data would suggest that, if anything, antipsychotic drug treatment can actually improve sleep quality in schizophrenia (Cohrs 2008; Krystal et al. 2008)....
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...More specifically, schizophrenia patients treated with typical antipsychotics show an increase in their sleep efficiency and total sleep time (Cohrs 2008)....
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...Today, sleep and circadian rhythm dis- ruption (SCRD) is reported in 30–80 % of patients with schizophrenia, and is increasingly recognised as one of the most common features of the disorder (Cohrs 2008)....
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TL;DR: Reduced sleep spindles seem to play an important role as a possible mechanism or biomarker for impaired sleep-related memory consolidation in patients with schizophrenia, and are a new target for treatment to improve memory functions and clinical outcomes in these patients.
99 citations
TL;DR: Orexin is involved in a number of other functions including reward and feeding, where OX1R (possibly OX2R) antagonists display anti-addictive properties in rodent models of alcohol, smoking, and drug self-administration, nor have they shown marked effects on weight in the existing clinical trials.
95 citations
Cites background from "Sleep disturbances in patients with..."
...…REM sleep abnormalities are listed as one of the prominent endophenotypes of depression and other diseases (see Hasler et al., 2004; Fleming, 1994; Cohrs, 2008; Germain and Nielsen, 2003) manifesting as short REM latency, elevated REM density (increased eye movements during REM sleep), and…...
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...For instance, REM sleep abnormalities are listed as one of the prominent endophenotypes of depression and other diseases (see Hasler et al., 2004; Fleming, 1994; Cohrs, 2008; Germain and Nielsen, 2003) manifesting as short REM latency, elevated REM density (increased eye movements during REM sleep), and prolongation of the first REM period, as well as reduced total sleep time, sleep efficiency especially....
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TL;DR: It is suggested that SZ patients are frequently affected with sleep and circadian rhythm disruptions; these may have a negative impact on rehabilitation strategies and poor sleep may play a role in sustaining poor quality of life in Sz patients.
Abstract: Sleep disturbances are widespread in schizophrenia, and one important concern is to determine the impact of this disruption on self-reported sleep quality and quality of life (QoL). Our aim was to evaluate the sleep-wake cycle in a sample of patients with schizophrenia (SZ), and whether sleep patterns differ between patients with predominantly negative versus predominantly positive symptoms, as well as its impact on sleep quality and QoL. Twenty-three SZ outpatients were studied with 24 h continuous wrist-actigraphy during 7 days. The quality of sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI), and the self-reported QoL was evaluated with the World Health Organization Quality of Life - Abbreviated version (WHOQOL-Bref). About half of the studied population presented an irregular sleep-wake cycle. We found a trend for more disrupted sleep-wake patterns in patients with predominantly positive symptoms, who also had a trend self-reported worse quality of sleep and worse QoL in all domains. Overall, patients with worse self-reported QoL demonstrated worse sleep quality. Our findings suggest that SZ patients are frequently affected with sleep and circadian rhythm disruptions; these may have a negative impact on rehabilitation strategies. Moreover, poor sleep may play a role in sustaining poor quality of life in SZ patients.
94 citations
Cites background from "Sleep disturbances in patients with..."
...Atypical antipsychotics tend to improve sleep induction and/or sleep maintenance in SZ patients (Monti and Monti, 2004), and most atypical antipsychotics demonstrate an increase in total sleep time and/or sleep efficiency in SZ patients,with the exception of risperidone (Cohrs, 2008)....
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...Patients with schizophrenia (SZ) frequently experience sleep problems (Keshavan et al., 1990; Taylor et al., 1991; Tandon et al., 1992;Monti andMonti, 2004; Cohrs, 2008), like advanced sleep phase syndrome and hypersomnia with short naps (Wirz-Justice et al., 2001)....
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...However, because of the limited number of methodologically rigorous studies, no clear statement can be made about the influence of these variables on sleep structure (Cohrs, 2008)....
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...This suggests that sleep physiology might share a common substrate with SZ symptoms (Boivin, 2000; Poulin et al., 2003; Cohrs, 2008)....
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...To disentangle the effects of schizophrenia itself from the influence of medication on sleep is difficult (Cohrs, 2008), but it seems unlikely that treatment only could explain the differences between the groups....
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TL;DR: Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
Abstract: The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
18,358 citations
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01 Jan 1968
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TL;DR: The Brief Psychiatric Rating Scale (BRS) as mentioned in this paper was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change, and it is recommended for use where efficiency, speed, and economy are important considerations.
Abstract: The Brief Psychiatric Rating Scale was developed to provide a rapid assessment technique particularly suited to the evaluation of patient change. Sixteen symptom constructs which have resulted from factor analyses of several larger sets of items, principally Lorr's Multidimensional Scale for Rating Psychiatric Patients (MSRPP) (1953) and Inpatient Multidimensional Psychiatric Scale (IMPS) (1960), have been included for rating on 7-point ordered category rating scales. The attempt has been to include a single scale to record degree of symptomacology in each of the relatively independent symptom areas which have been identified. Some of the preliminary work which has led to the identification of primary symptom constructs has been published (Gorham & Overall, 1960, 1961, Overall, Gorharn, & Shawver, 1961). While other reports are in preparation, applications of the Brief Scale in both pure and applied research suggest the importance of presenting the basic instrument to the wider scientific audience at this time, together with recommendations for its standard use. The primary purpose in developing the Brief Scale has been the development of a highly efficient, rapid evaluation procedure for use in assessing treatment change in psychiatric patients while at the same time yielding a rather comprehensive description of major symptom characteristics. It is recommended for use where efficiency, speed, and economy are important considerations, while more detailed evaluation procedures, such as those developed by Lorr (1953, 1961) should perhaps be wed in other cases. In order to achieve the maximum effectiveness in use of the Brief Scale, a standard interview procedure and more detailed description of rating concepts are included in this report. In addition, each symptom concept is defined briefly in the rating scale statements themselves. Raters using the scale should become thoroughly familiar with the scale definitions presented herein, after which the rating scale statements should be sufficient to provide recall of the nature and delineation of each symptom area. , To increase the reliability of ratings, it is recommended that patients be interviewed jointly by a team of two clinicians, with the two raters making independent ratings at the completion of the interview. An alternative procedure which has been recommended by some is to have raters discuss and arrive at a
10,457 citations
TL;DR: Among the newer antipsychotic agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least, and the differences among newer agents may affect compliance with medication and health risk.
Abstract: OBJECTIVE: The purpose of this study was to estimate and compare the effects of antipsychotics—both the newer ones and the conventional ones—on body weight. METHOD: A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. RESULTS: Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg....
2,271 citations
TL;DR: A method of gravimetric planimetry by standard photographs offers a means to study the course of surface wounds more accurately than by clinical observation or by the pictorial record alone.
Abstract: obtain their surface in square centimeters. This simple method provides a means by objective measurements to make evident changes in the surface of wounds that are not apparent to the naked eye. Figure 1 shows the observations recorded with this method in a man of 42 years of age with hemiplegia and a decubital ulcer over the right buttock. The clinicians who had observed this wound daily had not noticed any remarkable change; however, it is quite obvious that the wound grew larger each time the treatment was changed, and that the use of an antibiotic was followed by a particularly striking enlargement of the lesion. In this instance the procedure of projection and gravimetric planimetry was repeated by different operators and a variation of ±5% was found (indicated by a cross-hatched area on Fig. 1). Figure 2 shows the same type of observation in a woman with hemiplegia and a decubital ulcer. This patient died from septicemia, and the decubital ulcer worsened with the general condition of the patient. A method of gravimetric planimetry by standard photographs offers a means to study the course of surface wounds more accurately than by clinical observation or by the pictorial record alone. References
2,201 citations