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 was found that depression mediated the cross-sectional association between sleep problems and paranoid symptoms only, adding to a growing body of evidence suggesting the mediation role of depression is more pronounced for paranoid-type psychotic symptoms as compared to other psychotic symptoms.
Abstract: There has been growing interest on the effect of sleep problems on psychotic and prodromal symptoms. The current study investigated cross-sectional relations between sleep problems and attenuated psychotic symptoms in a large sample of 740 youth at Clinical High Risk (CHR) for psychosis in an attempt to replicate previous findings and assess whether findings from general population samples and psychotic samples extend to this CHR sample. Sleep problems were found to be significantly positively associated with attenuated psychotic symptom severity. Sleep problems were also found to be more closely associated with certain specific prodromal symptoms (e.g., suspiciousness and perceptual abnormalities) than other attenuated psychotic symptoms. Further, we found that depression mediated the cross-sectional association between sleep problems and paranoid symptoms only. This adds to a growing body of evidence suggesting the mediation role of depression is more pronounced for paranoid-type psychotic symptoms as compared to other psychotic symptoms (e.g., hallucinations).
24 citations
TL;DR: A broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume is outlined, including findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition.
Abstract: Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.
24 citations
TL;DR: Results for various movement disorders all favoured olanzapine and people receiving paliperidone were more likely to experience extrapyramidal disorders and a consistent, significant elevation in serum prolactin was found for both men and women.
Abstract: Background Paliperidone, risperidone's active metabolite, is now available in an oral formulation for daily use, and an intramuscular formulation for monthly administration may follow shortly. Objectives To compare effects of oral paliperidone with any other treatment for people with schizophrenia and schizophrenia-like illnesses. Search strategy We searched the Cochrane Schizophrenia Group's Register (December 2006), and inspected references of identified studies for further trials. We contacted the manufacturers of paliperidone, the Food and Drug Administration, and authors of relevant trials for additional material. Selection criteria We included all relevant randomised trials. Data collection and analysis We independently selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate, we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). We calculated Weighted Mean Differences (WMD) for continuous data. Main results Five studies compared paliperidone with placebo. Fewer people left the studies early if they were randomized to paliperidone (n=1647, 5 RCTs, RR 0.68 CI 0.61 to 0.76, NNT 7 CI 6 to 9) and those receiving any dose of paliperidone were significantly more likely to have an improvement in global state (n=1420, 4RCTs, RR 0.69 CI 0.63 to 0.75, NNT 5 CI 4 to 6). People randomised to paliperidone were less likely to experience a recurrence of psychosis (n=1638, 5 RCTs, RR 0.45 CI 0.31 to 0.66, NNT 16 CI 13 to 26) than those allocated to placebo. Adverse effect data were not well reported but paliperidone does seem to produce a greater incidence of tachycardia than placebo (n=1638, 5 RCTs, RR1.88 CI 1.28 to 2.76, NNH 21 CI 11 to 90) and a consistent, significant elevation in serum prolactin was found for both men (n=413, 3 RCTs, WMD 27.68 CI 23.66 to 31.69) and women (n=252, 3 RCTs, WMD 87.39 CI 74.27 to 100.51). People receiving paliperidone were more likely to experience extrapyramidal disorders (n=1638, 5 RCTs, RR 2.21 CI 1.26 to 3.88, NNH 28 CI 12 to 129) and weight gain (n=769, 4 RCTs, WMD 1.07 CI 0.65 to 1.49, I-squared 78%) compared with those allocated to placebo. When compared with 10 mg/day olanzapine we found no differences between paliperidone and olanzapine for leaving in the short term (n=1332, 3 RCTs, RR 1.04 CI 0.89 to 1.21; 40% in both groups left by six weeks). Those receiving any dose of paliperidone were no more likely to have a recurrence of psychotic symptoms than those receiving 10 mg/day olanzapine (n=1327, 3 RCTs, RR 0.1.07 CI 0.64 to 1.76). Data from all three studies found paliperidone was less likely to produce a weight change than olanzapine (n=660, 3 RCTs, WMD -0.88 CI -1.38 to -0.37). Results for various movement disorders all favoured olanzapine. There are no clear data relating to social functioning, services use, quality of life, satisfaction and cost. Authors' conclusions In short-term studies, oral paliperidone is an antipsychotic that is more efficacious than placebo. We found its adverse effects to be similar to those of its parent compound, risperidone, with movement disorders, weight gain, and tachycardia all more common with paliperidone than placebo. In addition, paliperidone is associated with substantial increases in serum prolactin that may be associated with sexual dysfunction, although sexual functioning outcomes were not reported. At doses greater than 3 mg per day, oral paliperidone appears comparable in efficacy to oral olanzapine 10 mg per day. Regarding the critical comparison of oral paliperidone to risperidone, we have no information and are thus unable to determine if paliperidone has any advantages or disadvantages compared to its well-known parent compound.
24 citations
Additional excerpts
...…Aravagiri 2000, Aravagiri 2002, Aravagiri 2003, Awouters 2007, Canuso 2008, Canuso 2009a, Canuso 2009b, Citrome 2007, Cleton 2006, Cleton 2007b, Cohrs 2008, Danel 2008, Dirks 2006, Dlugosz 2007, Dolder 2008, Dopheide 2008, Emsley 2008, Feng 2008, Fowler 2008, Freudenmann 2009, Friberg 2009,…...
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TL;DR: Evidence that sleep and circadian rhythm disturbances constitute a fundamental component of schizophrenia is reviewed, as supported by both human studies and animal models with genetic mutations related to schizophrenia.
Abstract: Schizophrenia is a multifactorial disorder caused by a combination of genetic variations and exposure to environmental insults. Sleep and circadian rhythm disturbances are a prominent and ubiquitous feature of many psychiatric disorders, including schizophrenia. There is growing interest in uncovering the mechanistic link between schizophrenia and circadian rhythms, which may directly affect disorder outcomes. In this review, we explore the interaction between schizophrenia and circadian rhythms from 2 complementary angles. First, we review evidence that sleep and circadian rhythm disturbances constitute a fundamental component of schizophrenia, as supported by both human studies and animal models with genetic mutations related to schizophrenia. Second, we discuss the idea that circadian rhythm disruption interacts with existing risk factors for schizophrenia to promote schizophrenia-relevant behavioral and neurobiological abnormalities. Understanding the mechanistic link between schizophrenia and circadian rhythms will have implications for mitigating risk to the disorder and informing the development of circadian-based therapies.
23 citations
Cites background from "Sleep disturbances in patients with..."
...Indeed, up to 80% of individuals with schizophrenia exhibited difficulties with sleep (Cohrs, 2008), and sleep disturbances preceded prodromal psychotic symptoms in more than 77% of patients (Tan and Ang, 2001)....
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TL;DR: The results point towards a possible maladaptive interplay between unstable thalamocortical networks, resulting in sleep-cycle-specific instability patterns associated with schizophrenia pathophysiology.
23 citations
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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