非典型抗精神病药物的研究进展

简述近年来国外新上市的及正处于临床研究的一些非典型抗精神病药物喹硫平、齐拉西酮、哌罗匹隆、阿立哌唑、Iloperidone、JL13等，并讨论了它们的作用机制、临床应用、不良反应等方面的问题。     

新型非典型抗精神病药临床应用评价

目前非典型抗精神病药应用越来越广泛,有逐渐取代典型抗精神病药的趋势,不但用于精神分裂症的治疗,而且作为心境稳定剂治疗情感障碍。本文对非典型抗精神病药的概念、治疗阴性症状和较少锥体外系不良反应的机制、在精神分裂症和情感障碍治疗中的临床应用评价等文献进行综述,重点讨论奥氮平、利司哌酮、喹硫平、阿立哌唑、齐哌西酮、氨磺必利和哌罗匹隆。     

非典型抗精神病药物的研究进展

［摘要］查阅近年来有关非典型抗精神病药物的国内外文献。从药物作用机制和构效关系方面综述非典型抗精神病药物的最新研究进展。目前非典型抗精神病药物主要分为三大系列：①具有代表性的非典型抗精神病药物;②已经进入临床研究的非典型抗精神病药物;③潜在的非典型抗精神病药物。多巴胺受体基因的多态性在精神病治疗中起到重要的作用,是新的非典型抗精神病药物设计的研究方向。随着分子药理学和组合化学的发展、药物设计理论的进一步完善以及计算机辅助药物设计技术的广泛应用,越来越多的新型非典型抗精神病药物将会在更短的时间内应用于临床,更好地服务患者。     

新型抗精神病药物临床研究进展

新型抗精神病药主要包括氯氮平、奥氮平、利培酮、奎的平、齐拉西酮、阿立哌唑、舍吲哚。我们依据国内外相关文献资料，以临床案例为基础，经分析归纳整理，就其药理学特点、临床应用和不良反应作一综述，为临床用药提供参考。     

非典型抗精神病新药阿立哌唑的合成

目的：研究非典型抗精神病药阿立哌唑的合成路线及工艺。方法：通过优化反应溶剂、反应温度、反应时间及加料方式，以1-(2，3-二氯苯基)哌嗪盐酸盐为起始原料，经N-溴丁基化和O-烃基化合成了阿立哌唑。结果：合成了目标化合物，总收率85％，其化学结构经元素分析、红外光谱、核磁共振氢谱及质谱确证。结论：该方法适合工业化生产。     

抗精神病药物阿立哌唑临床应用评价

大量临床研究证实,阿立哌唑作为一种具有全新作用机制的非典型抗精神病药物,治疗精神分裂症疗效肯定,不易复发,不良反应小,是临床上较有价值的治疗药物.笔者就近几年国外对该药的临床研究和评价进行了综述.     

新型非典型抗精神病药:鲁拉西酮

鲁拉西酮为一新型非典型抗精神病药,属于苯并异噻唑衍生物,为多巴胺D_2和5-羟色胺2A(5-HT_(2A))受体拮抗剂。2010年10月28日美国食品和药物管理局批准鲁拉西酮上市,其商品名为Latuda,用于治疗成人精神分裂症。鲁拉西酮的有效剂量范围为40～120mg·d~(-1),推荐起始剂量为40mg·d~(-1),一般最大推荐剂量为80mg·d~(-1),应与食物同时服用。鲁拉西酮常见不良反应有嗜睡、静坐不能、恶心、帕金森病以及焦虑。本文对鲁拉西酮的药理作用、药动学、药物相互作用、临床评价和安全性等进行综述。     

新型非典型抗精神病药——鲁拉西酮

目的:全面介绍非典型抗精神病新药鲁拉西酮.方法:通过文献分析,对该药物及其药理学、药动学、临床评价、安全性药物相互作用等予以阐述.结果:该药有效性、安全性和耐受性均良好.结论:鲁拉西酮是临床上有效的抗精神病治疗药物,其临床应用空间有望得到进一步拓展.     

非典型抗精神病药物的副作用

抗精神病药物代谢副作用从上世纪开始已引起人们的关注，但主要是研究其对神经系统的作用。随着副作用案例的增多，人们发现其导致糖尿病的副作用更严重。本文检索Medline 1996年至2003年6月有关氨磺必利、阿立哌唑、氯氮平、奥氮平、喹硫平、利培酮、齐拉西酮及佐替平致糖尿病的文献报道，总结了这些药物的副作用及可能的作用机制，并为如何选用这些药物及用药期间注意事项提出了建议。     

新型抗精神病药物——帕利哌酮缓释片

帕利哌酮缓释片是一种非典型抗精神病药物,临床疗效肯定,锥体外系等不良反应相对较小,该文综述其药理作用,药动学,临床疗效及不良反应,为临床合理应用该药提供参考.     

非典型抗精神病药物临床应用进展

依据近年来国内外相关文献,对非典型抗精神病药物的作用机制、临床应用及药物不良反应进行综述.非典型抗精神病药物除了治疗精神分裂症外,还用于治疗心境障碍、边缘性人格障碍、强迫症、抽动-秽语综合征等精神障碍.研究较多的不良反应包括体重增加及血脂、血糖、催乳素水平升高等.     

新型非典型抗精神病药齐拉西酮

通过文献检索综述了齐拉西酮的作用机制、药代动力学及临床评价。齐拉西酮是一种安全、有效的非典型性抗精神病药，用于治疗精神分裂症和分裂情感性障碍。     

The new atypical antipsychotics: a review of pharmacoeconomic studies

The pharmacoeconomic evaluation of atypical antipsychotics for the treatment of schizophrenia involves documentation of clinical effectiveness, quality of life and medical cost outcomes. The findings of pharmacoeconomic studies assist psychiatrists and mental healthcare decision-makers in identifying therapies that provide the greatest benefit to patients at the most acceptable cost. The cost-effectiveness of the newer atypical antipsychotics has been examined using non-controlled cohort studies (either retrospective or prospective), modelling studies or randomised clinical trials. The evidence, from a variety of studies, indicates that clozapine is a cost-effective treatment for neuroleptic refractory schizophrenia. Risperidone and olanzapine may be cost neutral, or at best slightly cost saving, compared with conventional antipsychotics, although they do improve patient clinical effectiveness and quality of life outcomes. There is too little data on pharmacoeconomic outcomes for sertindole and quetiapine to make any conclusions about their cost-effectiveness in treating schizophrenia.     

Refractory schizophrenia and atypical antipsychotics

Treatment resistant or refractory schizophrenia is a difficult to define condition of largely unknown prevalence. For 10 years, clozapine has been the standard treatment in this condition and is recognized unequivocally as being effective. However, clozapine is sometimes poorly tolerated and has the potential for severe toxicity. Partly as a result of this, other atypicals have recently been evaluated as treatments for refractory schizophrenia. In order to evaluate the evidence base relating to the drug treatment of refractory schizophrenia, we developed a refractoriness rating based on previous work. Using this rating, we assessed all trials of atypicals in schizophrenia unresponsive to at least one drug. Overall, clozapine was consistently shown to be effective in refractory schizophrenia, even when stringently defined. Data relating to olanzapine and risperidone are equivocal at best, and there is some evidence to suggest that they are less effective than clozapine. There is essentially no cogent evidence to support the use of any other atypical in refractory schizophrenia. Clozapine remains the drug of choice in this condition.     

Paediatric uses of atypical antipsychotics

Antipsychotics are commonly prescribed to children and adolescents. With the relatively recent availability of the atypical antipsychotics, physicians have begun prescribing these agents to young people in the hope of finding safe, effective alternatives to the typical antipsychotics. This report reviews what is currently known about the use of the atypical antipsychotics in young people. Most of the currently available data are based on case reports and case series. The results of only a handful of prospective trials pertaining to the use of the atypical antipsychotics in youths have been reported. Based on the available information, it appears that clozapine has a role in juvenile treatment resistant schizophrenia. When considered as a group, the 'first-line' atypical antipsychotics risperidone, olanzapine and quetiapine appear to have promise as treatments for several neuropsychiatric disorders in young people. These conditions include psychotic, mood, disruptive, movement and pervasive developmental disorders. Unfortunately, as has historically been the case, the demand to address the clinical needs of young patients with neuropsychiatric disorders has outpaced empirically based information. This is particularly important because significant side effects can occur when children or adolescents are treated with atypical antipsychotics. Since there is a paucity of short-term and almost no long-term safety data pertaining to these agents in young people, careful consideration must be made prior to initiating atypical antipsychotic treatment for a child or teenager. Based upon what is known about these agents, a rational approach to the use of these drugs in juveniles is offered.     

Paediatric uses of atypical antipsychotics

Antipsychotics are commonly prescribed to children and adolescents. With the relatively recent availability of the atypical antipsychotics, physicians have begun prescribing these agents to young people in the hope of finding safe, effective alternatives to the typical antipsychotics. This report reviews what is currently known about the use of the atypical antipsychotics in young people. Most of the currently available data are based on case reports and case series. The results of only a handful of prospective trials pertaining to the use of the atypical antipsychotics in youths have been reported. Based on the available information, it appears that clozapine has a role in juvenile treatment resistant schizophrenia. When considered as a group, the ‘first-line’ atypical antipsychotics risperidone, olanzapine and quetiapine appear to have promise as treatments for several neuropsychiatric disorders in young people. These conditions include psychotic, mood, disruptive, movement and pervasive developmental disorders. Unfortunately, as has historically been the case, the demand to address the clinical needs of young patients with neuropsychiatric disorders has outpaced empirically based information. This is particularly important because significant side effects can occur when children or adolescents are treated with atypical antipsychotics. Since there is a paucity of short-term and almost no long-term safety data pertaining to these agents in young people, careful consideration must be made prior to initiating atypical antipsychotic treatment for a child or teenager. Based upon what is known about these agents, a rational approach to the use of these drugs in juveniles is offered.     

Tolerability of atypical antipsychotics.

Atypical antipsychotics are expected to be better tolerated than older antipsychotics because of their lower propensity to cause certain adverse effects. All atypical drugs have been shown to cause fewer acute extrapyramidal symptoms (EPS) than a standard typical agent (usually haloperidol) and some (clozapine, sertindole and quetiapine) appear to cause these effects no more often than placebo. In the longer term, clozapine, olanzapine and (less robustly) other atypical antipsychotics are thought to cause less tardive dyskinesia than typical antipsychotics. Problems caused by hyperprolactinaemia occur less often with some atypical antipsychotics than with typical drugs although risperidone and amisulpride appear to have no advantages in this respect. Other adverse effects may occur as frequently with some atypical antipsychotics as with some typical drugs. Clozapine, risperidone and quetiapine are known to cause postural hypotension; clozapine, olanzapine and quetiapine are clearly sedative; and anticholinergic effects are commonly seen with clozapine, and, much less frequently, with olanzapine. Some adverse effects are more frequent with atypical drugs. Idiosyncratic effects seem particularly troublesome with clozapine and, to a lesser extent, sertindole, olanzapine and zotepine. Bodyweight gain is probably more problematic with atypical antipsychotics than with typical drugs. Overall tolerability, as judged by withdrawals from therapy, is not clearly proven to be better with atypical drugs, although some individual trials do indicate an advantage with atypical agents. Differences in tolerability between individual atypical antipsychotics have not been clearly shown. The tolerability profile of atypical drugs certainly benefits from a lower incidence of acute EPS effects, along with less certain or less uniform benefits in symptomatic hyperprolactinaemia or tardive dyskinesia. Other, perhaps more trivial, adverse effects militate against their good tolerability, and effects such as bodyweight gain may severely reduce tolerability. Without clear advantages in tolerability in patient groups used in trials, drug choice in regard to adverse effects should continue to be on a patient to patient basis.     

非典型抗精神病药物的不良反应

非典型抗精神药物在临床疗效、安全性、耐受性等方面明显优于典型抗精神病药,但是仍存在一些不良反应。本文对非典型抗精神病药物氯氮平、利培酮、喹硫平、齐拉西酮、舍吲哚的不良反应进行综述。     

Selective prescribing of atypical antipsychotics

PURPOSE: The aim of the study was to investigate whether the most recent introduced atypical antipsychotics olanzapine and risperidone were preferentially prescribed to patients susceptible to develop extrapyramidal side effects (EPS) and those not responding adequately to typical antipsychotics. METHODS: Data were obtained from the Dutch PHARMO system that includes complete medication and hospital admission records of 675 000 residents of 14 Dutch cities. A total number of 129 new users of olanzapine and 142 new users of risperidone as well as 507 new users of typical antipsychotic drugs were identified from our database in the period of 1996-1998. The prevalence of markers of EPS, therapy resistance and therapy non-compliance were assessed in the period of 1 year prior to a new start of an antipsychotic. RESULTS: New use of olanzapine and risperidone was significantly associated with previous use of other antipsychotics (odds ratio 4.0, 95%CI: 2.5-6.7 and odds ratio 3.0, 95%CI: 2.0-4.7, respectively). New use of olanzapine and risperidone was also associated with previous use of anticholinergic drugs compared to users of typical antipsychotics (over three and two times more, respectively). This effect diminished when adjusted for previous use of antipsychotics. CONCLUSIONS: In particular olanzapine and also risperidone were selectively prescribed to patients formerly treated with other antipsychotics and to those susceptible for EPS. If not recognised or controlled for, observational studies comparing different antipsychotic drugs may produce biased results on efficacy or frequency of side effects for the different types of antipsychotics.