Cytokines in schizophrenia and the effects of antipsychotic drugs

Growing evidence suggests that the immune, endocrine, and nervous systems interact with each other through cytokines, hormones, and neurotransmitters. The activation of the cytokine systems may be involved in the neuropathological changes occurring in the central nervous system (CNS) of schizophrenic patients. Numerous studies report that treatment with antipsychotic drugs affects the cytokine network. Hence, it is plausible that the influence of antipsychotics on the cytokine systems may be responsible for their clinical efficacy in schizophrenia. This article reviews current data on the cytokine-modulating potential of antipsychotic drugs. First, basic information on the cytokine networks with special reference to their role in the CNS as well as an up-to-date knowledge of the cytokine alterations in schizophrenia is outlined. Second, the hitherto published studies on the influence of antipsychotics on the cytokine system are reviewed. Third, the possible mechanisms underlying antipsychotics' potential to influence the cytokine networks and the most relevant aspects of this activity are discussed. Finally, limitations of the presented studies and prospects of future research are delineated.     

Combination of "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder

BACKGROUND: This article reviews the published clinical data on treatment-resistant schizophrenic and schizoaffective patients managed with combinations of "atypical" antipsychotic medication. METHOD: A computerized MEDLINE literature search covering an 18-year period (1985-2003) was conducted. All pertinent papers on the subject of the use of combination "atypical" antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder were obtained with subsequent analysis and discussion of the retrieved data. RESULTS: The search identified 29 case reports and case series reports (172 patients) and one double-blind placebo-controlled trial (28 patients) describing the use of combination "atypical" antipsychotic medication (clozapine-risperidone; clozapine-sulpiride; clozapine-olanzapine; clozapine-quetiapine; olanzapine-sulpiride; olanzapine-quetiapine; risperidone-olanzapine; risperidone-quetiapine) in the treatment of resistant schizophrenic and schizoaffective patients. An overview of results suggests that the combinations were beneficial in the described patients with reduction of positive symptoms and occasionally negative symptoms. Significant adverse effects, while rare, were reported in a few cases and did not appear to different in nature from those managed on monotherapeutic regimens. CONCLUSION: Combinations of "atypical" antipsychotic medications are well tolerated and may be effective in the management of treatment refractory schizophrenia and schizoaffective disorder. However, further double-blind placebo-controlled trials are required in order to test and confirm these observations.     

Prodromal schizophrenia and atypical antipsychotic treatment

Early recognition and intervention in psychosis is the focus of more intensive research. In this paper, we critically review the ideas that have emerged in this field. We also propose a model or hypothesis for testing in the prodromal phase of schizophrenia. Attention to practical and ethical issues, particularly with the use of atypical antipsychotics in one arm of the protocol, is addressed. Studies by Yung and Falloon describe prodromal intervention with psychosocial strategies and time-limited low potency neuroleptics, respectively, that suggest benefits of such a model. Although we have respect for the DSM system, this paper is written more from a Bleulerian than Kraepelinian perspective in that we emphasize affective, cognitive, and negative symptoms in addition to positive symptoms. The paper recognizes the strong conceptual disagreements implicit in this area stemming not only from Kraepelin and Bleuler but work from the 1930s by Cameron. The clinical research advocated is timely in that the atypicals are more congruent to the Bleulerian conception with a neurodevelopmental hypothesis of schizophrenia. We also have exciting new imaging and genetic technologies to refine our concepts of schizophrenia and its prodromal and premorbid phases.     

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.     

Early prediction of antipsychotic response in schizophrenia

OBJECTIVE: The authors' goal was to examine the predictive value of early symptom changes indicating response to antipsychotic medication in schizophrenia. METHOD: One hundred thirty-one acutely ill patients with schizophrenia received 4 weeks of fluphenazine treatment. Brief Psychiatric Rating Scale (BPRS) ratings were obtained at baseline and weekly. The authors examined the relationship between changes in BPRS total score and each factor score following 1 week of treatment and ultimate response status, defined as a reduction of 20% or more in total BPRS score. RESULTS: None of the patients who [corrected] displayed an improvement of less than 20% in total [corrected] BPRS score and only 5% [corrected] of the [corrected] patients who displayed a reduction of less than 20% in BPRS thought disturbance [corrected] score after 4 weeks of treatment had been classified as responders at 1 week (i.e., 100% and 95% specificity) [corrected] CONCLUSIONS: These data suggest that patients with minimal improvement in positive symptoms during the first week of treatment with a typical antipsychotic are unlikely to respond to a 4-week trial. These data require confirmation and extension to studies with second-generation antipsychotics.     

Choices in antipsychotic therapy in schizophrenia.

Pharmacotherapy for the treatment of schizophrenia now consists, for the most part, of two groups of agents. The conventional antipsychotic agents are exemplified by chlorpromazine and haloperidol, and the atypical agents by clozapine, risperidone, olanzapine, and quetiapine. In this article, the history of the development of these two groups, and their advantages and disadvantages, are reviewed. Effectiveness, side-effect burden, mode of delivery, and cost are discussed. The new practice of "stalled or reversed taper" is described. The clinician now has a wider range of options from which to choose, but many clinical questions remain unanswered.     

精神分裂症患者用药依从性及复发情况的调查

目的 研究在自然非干预状态下影响精神分裂症患者服药依从性和复发率的因素,探讨精神分裂症患者出院后1年的服药依从性和复发情况.方法 在全国4家精神卫生中心随机抽取规定时间跨度内(2009年1-8月)任意2个月各中心出院的精神分裂患者的整体作为研究对象,采用病历调查和电话采访的方式,对精神分裂症患者出院后1年的治疗情况进行回顾性问卷调查.主要观察指标为依从率和出院后1年复发率.结果 共完成有效调查问卷537份,患者出院后1年服药依从率为57.9％,复发率为40.8％.服药依从者与不依从者复发率的差异有统计学意义,依从性与复发情况有关联(x2=34.62,P＜0.01;OR =0.31,OR值95％可信区间为0.21～0.46);经济水平与依从性有关联(x2 =12.43,P＜0.05;OR =2.59,OR值95％可信区间为1.51 ～4.42);共同居住人情况与复发率有关联(x2=12.37,P＜0.05;OR =0.31,OR值95％可信区间为0.11 ～ 0.91).结论 接受调查的精神分裂症患者出院1年后的用药依从性较高,复发率与国外研究相当;依从性、共同居住人情况可能影响复发率,经济水平可能影响依从性.     

住院精神分裂症患者抗精神病药物联合治疗的处方调查

目的了解住院精神分裂症患者抗精神病药物联合治疗(APP)的情况,为精神分裂症的临床用药提供参考。方法连续入组2014年1月1日-12月31日在广州医科大学附属脑科医院住院的精神分裂症患者,收集患者的社会人口学资料,使用临床总体印象量表-病情严重程度量表(CGI-SI)评估患者疾病严重程度,在患者出院日记录抗精神病药物的使用情况,比较接受单一抗精神病药物治疗患者(单药组)与接受APP患者(APP组)的临床特点,描述APP中具体抗精神病药物的使用情况。结果共入组801例住院精神分裂症患者,其中364例(45.4%)使用APP。与单药组相比,APP组发病年龄更小、本次住院时间和总病程更长、住院次数更多,差异均有统计学意义(P均0.05)。APP组中78.0%的患者为同时使用两种第二代抗精神病药物(SGA),常见的联用方式为利培酮(47.3%)、氯氮平(44.5%)和奥氮平(40.1%)联合另一种抗精神病药物。结论住院精神分裂症患者中,接受APP方案的患者发病较早且病程迁延;两种SGA联用是APP中最常见的疗法,APP方案中使用频率最高的药物依次为利培酮、氯氮平和奥氮平。     

Metabolomic mapping of atypical antipsychotic effects in schizophrenia

Schizophrenia is associated with impairments in neurotransmitter systems and changes in neuronal membrane phospholipids. Several atypical antipsychotic drugs induce weight gain and hypertriglyceridemia. To date, there has not been a comprehensive evaluation and mapping of global lipid changes in schizophrenia, and upon treatment with antipsychotics. Such mapping could provide novel insights about disease mechanisms and metabolic side effects of therapies used for its treatment. We used a specialized metabolomics platform 'lipidomics' that quantifies over 300 polar and nonpolar lipid metabolites (across seven lipid classes) to evaluate global lipid changes in schizophrenia and upon treatment with three commonly used atypical antipsychotics. Lipid profiles were derived for 50 patients with schizophrenia before and after treatment for 2-3 weeks with olanzapine (n=20), risperidone (n=14) or aripiprazole (n=16). Patients were recruited in two cohorts (study I, n=27 and study II, n=23) to permit an internal replication analyses. The change from baseline to post-treatment was then compared among the three drugs. Olanzapine and risperidone affected a much broader range of lipid classes than aripiprazole. Approximately 50 lipids tended to be increased with both risperidone and olanzapine and concentrations of triacylglycerols increased and free fatty acids decreased with both drugs but not with aripiprazole. Phosphatidylethanolamine concentrations that were suppressed in patients with schizophrenia were raised by all three drugs. Drug specific differences were also detected. A principal component analysis (PCA) identified baseline lipid alterations, which correlated with acute treatment response. A more definitive long-term randomized study of these drugs correlating global lipid changes with clinical outcomes could yield biomarkers that define drug-response phenotypes.     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较非经典抗精神病药奎硫平、奥氮平、氯氮平与经典抗精神病药氯丙嗪对精神分裂症患者认知功能的影响。方法：对160例住院精神分裂症患者随机开放分配接受奎硫平、奥氮平、氯氮平和氯丙嗪药物治疗。12周的急性期治疗后,获得临床稳定期的患者[阳性与阴性量表（PANSS）总分≤60或减分率／〉50％]进入固定剂量的24周治疗。分别在基线、治疗12周和24周进行威斯康星卡片分类测验（WCST）、言语流畅性测验、霍普金斯词语学习测验（HVLT-R）、持续操作功能测验（CPT）、韦克斯勒记忆测定（WMS）、韦克斯勒智能测定（WAIS）、连线试验测定、手指叩击试验测定。结果：奎硫平组、奥氮平组、氯氮平组治疗12周和24周后认知功能均有不同程度的改善（P均〈0．05）,明显优于氯丙嗪,而氯丙嗪组无显著改善。治疗12周后奎硫平组在改善执行功能、言语流畅性和警觉性显著优于奥氮平组和氯氮平组（P〈0．05）。奥氮平组在数字特征和连线测定上明显优于氯氮平组（P〈0．05）。3种非经典抗精神病药在认知功能总分的改善与PANSS总分、阴性症状分的改善有显著相关性（r=-0．32,P〈0．05）。结论：3种非经典抗精神病药奎硫平、奥氮平、氯氮平可不同程度改善精神分裂症患者的认知功能。