Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population

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 1 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.     

Effects of typical antipsychotic drugs and risperidone on the quality of sleep in patients with schizophrenia: a pilot study.

OBJECTIVE: To investigate the effects of a newer antipsychotic drug, risperidone (a potent serotonin 5-HT2A/2C and dopamine D2-receptor blocker), on the quantity and quality of sleep in patients with schizophrenia. DESIGN: Prospective pilot study. SETTING: Outpatient treatment at a mental health hospital. PATIENTS: Two groups of age- and sex-matched patients with schizophrenia receiving either risperidone (n = 8) or a typical antipsychotic drug (n = 8), and a group of age- and sex-matched controls (n = 8). OUTCOME MEASURES: Sleep quality, measured by a visual analogue scale, and sleep continuity, measured using a movement index calculated from actigraph data. RESULTS: Patients with schizophrenia had more disturbed sleep than controls. Compared with patients treated with typical antipsychotic drugs, patients treated with risperidone reported significantly better sleep quantity and quality as well as general functioning. CONCLUSION: Improvement by risperidone may be related to 5-HT2A/2C receptor blockade; however, further controlled studies are required to confirm these results.     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

Predictors of improvement in subjective sleep quality reported by older adults following group-based cognitive behavior therapy for sleep maintenance and early morning awakening insomnia

ObjectiveCognitive behavior therapy is an effective nonpharmacologic treatment for insomnia. However, individualized administration is costly and often results in substantial variability in treatment response across individual patients, particularly so for older adults. Group-based administration has demonstrated impressive potential for a brief and inexpensive answer to the effective treatment of insomnia in the older population. It is important to identify potential predictors of response to such a treatment format to guide clinicians when selecting the most suitable treatment for their patients. The aim of our study was to identify factors that predict subjective sleep quality of older adults following group-based administration of cognitive behavior therapy for insomnia (CBT-I).MethodsEighty-six adults (41 men; mean age, 64.10 y; standard deviation [SD], 6.80) with sleep maintenance or early morning awakening insomnia were selected from a community-based sample to participate in a 4-week group-based treatment program of CBT-I. Participants were required to complete 7-day sleep diaries and a comprehensive battery of questionnaires related to sleep quality and daytime functioning. Hierarchical multiple regression analyses were used to identify factors predicting subjective sleep quality immediately following treatment and at 3-month follow-up. Sleep diaries reported average nightly sleep efficiency (SE), which was used as the outcome measure of sleep quality.Results and conclusionsParticipants with the greatest SE following treatment while controlling for pretreatment SE were relatively younger and had more confidence in their ability to sleep at pretreatment. These characteristics may be useful to guide clinicians when considering the use of a group-based CBT-I for sleep maintenance or early morning awakening insomnia in older adults.     

Weight change and atypical antipsychotic treatment in patients with schizophrenia

Schizophrenic patients who have been prescribed atypical antipsychotics have a potential risk of gaining weight. The implications of weight gain for clinical care may differ depending on whether a patient is underweight or overweight at baseline. The exact mechanism for weight gain is not known, but several factors have been identified that can help predict which patients are at risk for gaining weight. These factors include better clinical outcome, increased appetite, and low baseline body mass index. In patients treated with olanzapine for up to 3 years, weight gain trended toward a plateau at approximately 36 weeks. Weight gain interventions, including behavioral modifications, show promise in controlling or reducing weight in patients treated with antipsychotics.     

Assessment of physical activity in middle-aged and older adults with schizophrenia

BACKGROUND: Regular physical activity (PA) decreases morbidity in the general population; yet, information about the amount and effects of PA in persons with schizophrenia is scant. To develop interventions to increase PA and to assess its potential benefits in this group, accurate measurement of PA is needed. The purpose of this study was to characterize PA and determine the test-retest reliability and concurrent validity of the Yale Physical Activity Scale (YPAS), a self-report measure, in persons with schizophrenia. METHODS: PA was assessed with the YPAS, a scale of motivational readiness for PA, and accelerometry in middle-aged and older persons with a diagnosis of schizophrenia (n=54) and in a comparison group with no known psychiatric diagnosis (n=27). RESULTS: On the YPAS measures, persons with schizophrenia reported on average 11 h per week of PA, whereas the non-psychiatric comparison group reported about 32 h per week. Only about 30% of schizophrenia subjects were classified as being regularly active relative to 62% of the comparison group on PA motivational stages of readiness. On the accelerometry measures, the schizophrenia group had lower levels of light activity than the comparison group, but there were no differences in moderate and vigorous activity or sedentary behavior. Only in the comparison group were there significant associations between YPAS and accelerometer variables. Several YPAS scores demonstrated high test-retest reliability in both groups, and concurrent validity was supported between the YPAS and PA motivational stages of readiness. CONCLUSIONS: We found that the YPAS is a reliable measure of PA in schizophrenia for some indices. Although the YPAS demonstrated concurrent validity with other self-report measures, it did not demonstrate concurrent validity when compared to PA measured by accelerometry in persons with schizophrenia. Use of multiple measures, both subjective and objective, is recommended when assessing PA in schizophrenia.     

Insight, quality of life, and functional capacity in middle-aged and older adults with schizophrenia

OBJECTIVE: The quality of life (QOL) for individuals with schizophrenia is determined by a number of factors, not limited to symptomatology. The current study examined lack of insight as one such factor that may influence subjective QOL or functional capacity. It was hypothesized that insight would significantly interact with symptom severity to influence subjective QOL. Insight was not expected to influence the relation between symptom severity and functional capacity. METHODS: Participants were middle-aged and older outpatients who met diagnostic criteria for schizophrenia or schizoaffective disorder, and subsyndromal depression. Insight, psychopathology, and subjective QOL were assessed via semi-structured interviews and functional capacity was assessed via performance-based measures. RESULTS: Insight interacts with negative symptom severity to predict subjective QOL. Severity of negative symptoms and insight contribute directly to functional capacity. CONCLUSIONS: Individuals with intact insight may be better able to manage their symptoms, resulting in improved QOL. Treatment implications for improving the QOL of middle age and older adults with schizophrenia are discussed.     

The impact of prolactin elevation with antipsychotic medications on subjective quality of life in patients with schizophrenia

In this cross-sectional study, the author tested the hypothesis that prolactin elevation with antipsychotic medications was associated with low subjective quality-of-life scores in patients with schizophrenia. The subjects were 42 male inpatients meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia on typical antipsychotics. No correlations were found between prolactin or testosterone and the 3 subscales in the Japanese version of the Schizophrenia Quality of Life Scale. Multiple regression analyses showed total variance in the ratings of 3 subscales in the Japanese version of the Schizophrenia Quality of Life Scale as follows: Brief Psychiatric Rating Scale (BPRS) anxiety/depression factor, dosage of antipsychotics and BPRS hostile/suspiciousness factor in the psychosocial subscale (adjusted R2 = 0.394), BPRS anxiety/depression factor and dose of antipsychotics in the motivation/energy subscale (adjusted R2 = 0.475), and dose of antipsychotics and BPRS anergia factor in the symptoms/side effects subscale (adjusted R2 = 0.206). The results did not support the hypothesis.     

四种非典型抗精神病药对血清催乳素和血脂的影响

目的探讨四种非典型抗精神病药对精神分裂症患者血脂和血清催乳素（PRL）的影响,以及血清PRL水平与药物疗效的关系。方法118例精神分裂症患者分为4组,分别予以喹硫平（29例）、氯氮平（30例）、奥氮平（30例）和利培酮（29例）治疗12周。于治疗前及治疗4、8及12周末予以阳性与阴性症状量表（PANSS）评定,测定血总胆固醇（TC）、甘油三脂（TG）高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、阿朴脂蛋白A—I（ApoA-1）、阿朴脂蛋白-B（Apo—B）及血清PRL浓度。结果（1）喹硫平组TG、HDL在12周末有显著升高（P〈0．05）,氯氮平组Apo—B在4、12周末有显著升高（P〈0．05）、LDL在8、12周末有显著升高（P〈0．05）,利培酮组除TG外其余血脂指标在8、12周末有显著升高（P〈0．05）,奥氮平组TG、HDL、LDL、ApoA-1、Apo—B在12周末有显著升高（P〈0．05）,TC在8与12周有显著升高（P〈0．05）。（2）利培酮组治疗8、12周后血清PRL明显升高（P〈0．01）。（3）氯氮平组和利培酮组PANSS一般病理分的减分率分别与PRL、LDL有显著相关;氯氮平组PRL与LDL有显著相关。结论利培酮、奥氮平、喹硫平和氯氮平均影响血脂代谢;氯氮平疗效与血清催乳素及LDL有关,利培酮疗效与LDL有关。     

Depression in schizophrenia: comparison of first- and second-generation antipsychotic drugs

The aim of this study was to compare the effects of different antipsychotics on depressive symptoms in schizophrenic patients. The data were drawn from a retrospective, naturalistic, observational study in which 222 subjects diagnosed as being affected by schizophrenia during a re-exacerbation phase received 6 weeks of monotherapy with fluphenazine decanoate, haloperidol decanoate, haloperidol, clozapine, olanzapine, quetiapine, risperidone or l-sulpiride. The Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Side Effects Rating Scale (EPSE) and Anticholinergic Rating Scale (ACS) were administered at baseline and six weeks after the beginning of the study; depressive symptoms were evaluated using the BPRS items "depressive mood" and "guilt feelings". All of the antipsychotic drugs led to improvements in the depressive dimension, but this was statistically significant only in the case of fluphenazine decanoate, haloperidol, olanzapine, risperidone and l-sulpiride. A clinical improvement in the depressive dimension significantly correlated with the severity of the psychotic picture and its amelioration. Female patients were significantly more likely to show an improvement in depressive symptoms. In conclusion, our findings suggest that atypical antipsychotics as a class do not seem to be more effective on the depressive dimension during the course of schizophrenia than typical ones, at least as far as the collected BPRS data are concerned. The only factor that seemed to influence the improvement in depressive symptoms during our study was gender, as females were significantly more likely to improve although there were no between-gender differences in the baseline severity of the clinical picture.     

The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis.

Cognitive deficits are a fundamental feature of the psychopathology of schizophrenia. Yet the effect of treatment on this dimension of the illness has been unclear. Atypical antipsychotic medications have been reported to reduce the neurocognitive impairment associated with schizophrenia. However, studies of the pattern and degree of cognitive improvement with these compounds have been methodologically limited and have produced variable results, and few findings have been replicated. To clarify our understanding of the effects of atypical antipsychotic drugs on neurocognitive deficits in patients with schizophrenia, we have (1) reported on newly established standards for research design in studies of treatment effects on cognitive function in schizophrenia, (2) reviewed the literature on this topic and determined the extent to which 15 studies on the effect of atypical antipsychotics met these standards, (3) performed a meta-analysis of the 15 studies, which suggested general cognitive enhancement with atypical antipsychotics, and (4) described the pharmacological profile of these agents and considered the pharmacological basis for their effects on neurocognition. Finally, we suggest directions for the development of new therapeutic strategies.     

Citalopram augmentation of antipsychotic treatment in older schizophrenia patients.

BACKGROUND: Depressive symptoms are common in older patients with schizophrenia; yet, few studies have examined the usefulness of antidepressants in this population. OBJECTIVE: We conducted a 10-week single-blind trial of citalopram (20-40 mg/day) vs no citalopram augmentation in 19 middle-aged and elderly patients with schizophrenia hospitalized for more than six of the last 12 months. At study-entry, the patients had been on stable doses of antipsychotics for at least two weeks, and had a 17-item Hamilton Depression Rating (HAM-D) scale score of 12 or greater. Nine patients were randomly assigned to citalopram augmentation, and 10 to no augmentation of antipsychotics. RESULTS: Patients in both groups improved on positive and negative symptoms, but the citalopram group had significantly greater improvement in HAM-D and Clinical Global Impression Scale scores than the control group. There were no major side effects. CONCLUSION: Larger double-blind studies are needed to follow up on these preliminary findings.     

Social networks and alcohol use among older adults: a comparison with middle-aged adults

Objectives: This study compared the association between social networks and alcohol consumption among middle-aged (MA) and older adults (OA) to better understand the nature of the relationship between those two factors among OA and MA.

Method: We examined Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Current drinkers aged over 50 were subdivided into two age groups: MA (50–64, n = 5214) and OA (65 and older, n = 3070). Each age group was stratified into drinking levels (low-risk vs. at-risk) based on alcohol consumption. The size and diversity of social networks were measured. Logistic regression models were used to examine age differences in the association between the social networks (size and diversity) and the probability of at-risk drinking among two age groups.

Results: A significant association between the social networks diversity and lower odds of at-risk drinking was found among MA and OA. However, the relationship between the diversity of social networks and the likelihood of at-risk drinking was weaker for OA than for MA. The association between social networks size and at-risk drinking was not significant among MA and OA.

Conclusion: The current study suggests that the association between social networks diversity and alcohol use among OA differs from the association among MA, and few social networks were associated with alcohol use among OA. In the future, research should consider an in-depth exploration of the nature of social networks and alcohol consumption by using longitudinal designs and advanced methods of exploring drinking networks.     

Estimating the costs and benefits of new drug therapies: atypical antipsychotic drugs for schizophrenia

This article presents an analytic tool populated with data from published studies to illustrate the likely impacts of a switch from typical to atypical antipsychotic drugs over a 3-year period on individual, family, and societal outcomes for a U.S. schizophrenia population. Data taken from clinical trials and observational data studies are used. Changes in annual health care costs, schizophrenia symptom days, extrapyramidal symptom (EPS) days, suicide rates, and employment days are estimated. For each 1,000 people treated with typical drugs, the base case scenario gives estimates of annual medical care costs of dollar 28.9 million with 80,253 moderate/severe schizophrenia symptom days and 92,006 EPS days. In the base case scenario, after switching to atypical drugs, schizophrenia symptom days are estimated to decrease up to 33 percent, EPS days up to 50 percent, and total medical care costs up to 19 percent over the 3-year period. Suicide rates fall and employment rates increase. The direction of the impacts remain the same for a wide range of input parameter values used in sensitivity analyses. Thus, switching to atypical drugs will likely reduce total medical care costs and decrease other disease burdens for people with schizophrenia, their families, and society.     

Sleep in schizophrenia patients and the effects of antipsychotic drugs

Insomnia is a common feature in schizophrenia. However, it seldom is the predominant complaint. Nevertheless, severe insomnia is often seen during exacerbations of schizophrenia, and may actually precede the appearance of other symptoms of relapse. The sleep disturbances of either never-medicated or previously treated schizophrenia patients are characterized by a sleep-onset and maintenance insomnia. In addition, stage 4 sleep, slow wave sleep (stages 3 and 4), non-REM (NREM) sleep in minutes and REM latency are decreased. The atypical antipsychotics olanzapine, risperidone, and clozapine significantly increase total sleep time and stage 2 sleep. Moreover, olanzapine and risperidone enhance slow wave sleep. On the other hand, the typical antipsychotics haloperidol, thiothixene, and flupentixol significantly reduce stage 2 sleep latency and increase sleep efficiency. Future research should address: (1) the sleep patterns in subtypes of schizophrenia patients; (2) the role of neurotransmitters other than dopamine in the disruption of sleep in schizophrenia; (3) the functional alterations in CNS areas related to the pathophysiology of schizophrenia during NREM sleep and REM sleep (brain imaging studies); (4) the short-term, intermediate-term, and long-term effects of atypical antisychotics on sleep variables.     

Serum lipid profiles and schizophrenia: effects of conventional or atypical antipsychotic drugs in Taiwan

This study investigated the relationships between serum lipid profiles and schizophrenia and the effects of conventional or atypical antipsychotic drugs on serum lipid profiles. During a 1-year period, fasting blood samples for serum lipid profiles were collected from 126 schizophrenic patients and 59 healthy control subjects. The serum lipid profiles were detected by enzymatic determination. Patients were assessed for disease severity at baseline and endpoint at 3 weeks using the Positive and Negative Syndrome Scale. At baseline, patients with acute-phase schizophrenia had lower high-density lipoprotein (HDL) levels, higher low-density lipoprotein (LDL) levels, and higher ratios of total cholesterol/high-density lipoprotein (TC/HDL) and LDL/HDL than healthy control subjects. At endpoint, after a 3-week treatment with antipsychotics, the blood samples of the 97 schizophrenic patients were assessed again. Responders to antipsychotic treatment (n = 68) but not nonresponders (n = 29) had significantly increased TC, triglyceride (TG), and very low-density lipoprotein (VLDL) levels and decreased ratio of LDL/HDL. Experimental findings also showed significantly increased TC, TG, HDL, and VLDL levels and decreased ratio of LDL/HDL in responders taking atypical antipsychotic drugs (n = 32), but not in patients treated with conventional antipsychotic drugs (n = 36). In conclusion, this study identified strong associations between dyslipidemia and acute-phase schizophrenia and dyslipidemia and responders taking atypical antipsychotics; both associations would increase the risk of developing diabetes and coronary heart disease.     

Waking EEG functional connectivity in middle-aged and older adults with obstructive sleep apnea

ObjectivesThe present study aimed at investigating changes in waking electroencephalography (EEG), most specifically regarding spectral power and functional connectivity, in middle-aged and older adults with obstructive sleep apnea (OSA). We also explored whether changes in spectral power or functional connectivity are associated with polysomnographic characteristics and/or neuropsychological performance.MethodsIn sum, 19 OSA subjects (apnea-hypopnea index ≥ 20, age: 63.6 ± 6.4) and 22 controls (apnea-hypopnea index ≤ 10, age: 63.6 ± 6.7) underwent a full night of in-laboratory polysomnography (PSG) followed by a waking EEG and a neuropsychological assessment. Waking EEG spectral power and imaginary coherence were compared between groups for all EEG frequency bands and scalp regions. Correlation analyses were performed between selected waking EEG variables, polysomnographic parameters and neuropsychological performance.ResultsNo group difference was observed for EEG spectral power for any frequency band. Regarding the imaginary coherence, when compared to controls, OSA subjects showed decreased EEG connectivity between frontal and temporal regions in theta and alpha bands as well as increased connectivity between frontal and parietal regions in delta and beta 1 bands. In the OSA group, these changes in connectivity correlated with lower sleep efficiency, lower total sleep time and higher apnea-hypopnea index. No relationship was found with neuropsychological performance.ConclusionsContrary to spectral power, imaginary coherence was sensitive enough to detect changes in brain function in middle-aged and older subjects with OSA when compared to controls. Whether these changes in cerebral connectivity predict cognitive decline needs to be investigated longitudinally.     

The effect of treatment with antipsychotic drugs on brain N-acetylaspartate measures in patients with schizophrenia.

BACKGROUND: The specific intracellular effects of antipsychotic drugs are largely unknown. Studies in animals have suggested that antipsychotics modify the expression of various intraneuronal proteins, but no analogous in vivo data in humans are available. The objective of the present study was to assess whether antipsychotics modify N-acetylaspartate (an intraneuronal marker of neuronal functional integrity) measures in brains of patients with schizophrenia. METHODS: We used proton magnetic resonance spectroscopic imaging to study 23 patients with schizophrenia (DSM-IV diagnosis) using a within-subject design. Patients were studied twice: once while on a stable regimen of antipsychotic drug treatment (for at least 4 weeks) and once while off medication for at least 2 weeks. Several cortical and subcortical regions were assessed, including the dorsolateral prefrontal cortex and the hippocampal area. RESULTS: Analysis of variance showed that, while on antipsychotics, patients had significantly higher N-acetylaspartate measures in the dorsolateral prefrontal cortex (p =.002). No other region showed any significant effect of treatment. CONCLUSIONS: These results indicate that antipsychotic drugs increase N-acetylaspartate measures selectively in the dorsolateral prefrontal cortices of patients with schizophrenia, suggesting that these drugs modify in a regionally specific manner the function of a population of cortical neurons. N-Acetylaspartate measures may provide a useful tool to further investigate the effects of antipsychotics at the intracellular level.