新一代非典型抗精神病药

对近几年出现的一些非典型抗精神病药物利培酮、奥氮平、喹硫平、齐拉西酮、舒吲哚进行了分析,并讨论了这些新药的作用机制、不良反应、临床应用、过量时危险及处理等几个方面的问题。     

非典型抗精神病药物的代谢途径

非典型抗精神病药的代谢主要由细胞色素P450催化，氮平主要由CYP1A2和CYP3A4催化代谢成去甲氯氮平和N－氧化氯氮平；利培酮由CYP2D6和CYP3A4催化代谢生成9－羟利培酮；奥氮平由CYP1A2、CYP2D6催化代谢成2－羟基甲基奥氮平、4′－N－氧化物等；硅硫平主要通过CYP3A4催化代谢生成7－羟基代谢产物；齐哌西酮由CYP3A4催化代谢生成硫氧化物等代谢产物；思庭多由CYP2D6催化代谢成脱氢思庭多和由CYP3A4代谢为去甲基－思庭多。正常人使用非典型抗精神病药可以导致强烈的镇静作用，因此研究药物的代谢时，其剂量远低于临床治疗剂量。临床治疗剂量的药物代谢值得进一步研究。     

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物的应用及研究进展

典型抗精神病药能减少精神分裂症的阳性症状,却伴发锥体外系不良反应。新型非典型抗精神病药物相比已有的典型抗精神病药物,具有疗效好、不良反应小等优点,有望为精神分裂症的治疗开创新的局面。本文从药物应用方面综述了自2000年上市的一些非典型抗精神病药物的最新研究进展,期待越来越多的新型非典型抗精神病药物能应用于临床,更好地服务患者。     

新型抗精神病药：哌罗匹隆

哌罗匹隆是一种新型非典型抗精神病药,主要药理机制是5-羟色胺(5-HT)和多巴胺D_2受体拮抗作用。与传统抗精神病药相比,哌罗匹隆对阳性症状、阴性症状和情感症状均有较好疗效,锥体外系不良反应和致催乳素升高作用轻微。哌罗匹隆是一种安全有效的非典型抗精神病药。     

新型抗精神病药氨磺必利

近 1 5a来 ,以阴性症状为主的精神分裂症越来越引起人们的关注。现已认识到 ,这一类患者部分的阴性症状是单纯、原发的 ,并可能与多巴胺能功能减弱有关 ,故对经典抗精神病药物疗效欠佳。因此 ,有必要寻找新型治疗药物。氨磺必利 (amisulpride,ASP) ,商品名 Solian,是由 Sanofi- Synthelabo公司开发的一种针对阴性症状具有显著优点的新型非经典抗精神病药物 ,系苯甲酰胺类衍生物 ,化学名称 4-氨基 -氮 - 1 - [(1 -乙基 - 2吡咯烷 )甲基 ]- 5-乙基磺酰 - 2 -甲氧基苯甲酰胺[4- amino- N- 1 [(1 - ethyl- 2 - pyrrolidinyl) methyl]- 5-(eth…     

齐哌西酮--一种新型非典型抗精神病药物

2001年2月被美国FDA批准用于精神科临床治疗精神分裂症的一种新型、非典型抗精神病药物--齐哌西酮(ziprasidone,或被译为齐拉西酮、力复君安)[1]即将在我国上市.该药除有片剂外,尚有针剂可供使用.鉴于目前在精神科控制精神分裂症患者急性激越症状的药物选择多为氟哌啶醇和氯丙嗪,因此作为临床上首个以非典型抗精神病药物针剂来控制精神疾病的药物出现,当会引人注目.齐哌西酮由美国辉瑞公司(Pfize)研制,已在美国和日本分别进行Ⅲ期和Ⅱ期临床试验[2].国产齐哌西酮(商品名:力复君安),由重庆圣华曦药业有限公司生产,初步定于上市时间为2005年12月.为便于临床医生了解该药情况,现略作介绍.     

齐哌西酮--一种新型非典型抗精神病药物

2001年2月被美国FDA批准用于精神科临床治疗精神分裂症的一种新型、非典型抗精神病药物--齐哌西酮(ziprasidone,或被译为齐拉西酮、力复君安)[1]即将在我国上市.该药除有片剂外,尚有针剂可供使用.鉴于目前在精神科控制精神分裂症患者急性激越症状的药物选择多为氟哌啶醇和氯丙嗪,因此作为临床上首个以非典型抗精神病药物针剂来控制精神疾病的药物出现,当会引人注目.齐哌西酮由美国辉瑞公司(Pfize)研制,已在美国和日本分别进行Ⅲ期和Ⅱ期临床试验[2].国产齐哌西酮(商品名:力复君安),由重庆圣华曦药业有限公司生产,初步定于上市时间为2005年12月.为便于临床医生了解该药情况,现略作介绍.     

非典型抗精神病药物在儿童多发性抽动障碍治疗中的研究进展

多发性抽动障碍（TS）是儿童期常见的神经精神疾病,临床特征表现为运动性抽动和发声性抽动,抽动症状在青春期后有所改善,但部分患者可能出现抽动相关的共患病。在传统治疗措施失败,且某些精神合并症使临床表现复杂化时,非典型抗精神病药物成为治疗TS的新选择。然而,非典型精神病药物治疗TS的研究证据比较有限。研究证据显示,非典型性抗精神病药物广泛应用于TS的治疗,其中利培酮是研究证据相对充足的有效药物,阿立哌唑是治疗TS具有较好前景的药物,齐拉西酮、奥氮平与喹硫平能改善抽动症状,但随机对照试验缺乏,有待进一步研究证实。甲氧氯普胺和氯氮平研究证据缺乏,且副作用明显,不推荐用于治疗TS。     

新剂型非典型抗精神病药富马酸喹硫平缓释片的研究进展

富马酸喹硫平缓释片作为非典型抗精神病药物喹硫平的缓释剂型,在国际上被广泛用于精神分裂症、双相躁狂、双相抑郁、双相维持期和广泛性焦虑障碍治疗以及抑郁症的联合治疗,每天只需用药1次,2 d内迅速达到目标剂量范围,在不降低疗效的前提下提高了患者的依从性,睡前3~4 h服用,可明显减少日间的镇静不良反应。多项临床试验证实了该剂型临床应用的安全性与有效性。     

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.     

Atypical antipsychotics in the treatment of bipolar disorder

Atypical antipsychotic medications are widely used for the treatment of bipolar disorder. Most empirical support suggests that these medications are efficacious in the treatment of acute mania, but there is considerably less support for the utility of these drugs in other phases of bipolar disorder. However, it is likely that several of these drugs will demonstrate efficacy in relapse prevention, and perhaps antidepressant efficacy in bipolar disorder as more studies are conducted. Atypical antipsychotics offer different side effect profiles than older antipsychotics, which may be of benefit for some patients. Consequently, atypical antipsychotics provide an important treatment option for bipolar patients.     

The use of antipsychotics in children and adolescents with bipolar disorders

The use of antipsychotics, particularly the atypical antipsychotics, has increased dramatically in child and adolescent populations over the last decade. This class of psychotropics has been used to treat a variety of psychiatric disorders in pediatric populations, including bipolar disorder (BPD). The present clinical guidelines for treating BPD in younger populations closely follow those for managing adult BPD, as reasoning for using the atypicals is many times initially based on the outcomes of adult studies and indications. As in adult populations, metabolic parameters such as body mass index, blood glucose levels and fasting lipid profiles should be routinely monitored throughout the course of treatment. Of the several studies undertaken thus far, it appears that atypical antipsychotics are efficacious in the treatment of pediatric BPD. However, the number of controlled studies demonstrating their efficacy in younger subjects is limited and further investigation is required to evaluate if effectiveness and potential for side effects differ significantly than that for adult populations.     

Neuroleptic malignant syndrome induced by atypical antipsychotics

A review of the English literature confirms that neuroleptic malignant syndrome (NMS) occurs with both traditional and atypical antipsychotic medications. Published reports of NMS induced by the traditional antipsychotics have given the practitioner valuable information on the prevention and treatment of this adverse effect. Case reports have also been published concerning NMS and clozapine, risperidone, olanzapine and quetiapine. By evaluating the case reports of atypical antipsychotic-induced NMS, valuable information may be obtained concerning similarities or differences from that induced by the traditional antipsychotics. The case reports of NMS with atypical antipsychotics were evaluated for diagnosis, age/sex of patient, risk factors, antipsychotic doses and duration of use, symptoms of NMS, and clinical course.     

非典型抗精神病药物血液系统不良事件信号挖掘和数据分析

目的 基于美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）挖掘6种非典型抗精神病药物氯氮平、奥氮平、阿立哌唑、喹硫平、利培酮、齐拉西酮血液系统不良事件（ADE）信号,为临床安全使用非典型抗精神病药物提供参考。方法 下载2017年第1季度—2021年第3季度共19个季度的FAERS数据,采用比值失衡法中的报告比值比（ROR）法和综合标准法（MHRA）检测数据库中非典型抗精神病药物的ADE信号,统计并分析血液系统ADE信号的相关信息。结果 从FAERS数据库得到以氯氮平、奥氮平、阿立哌唑、利培酮、喹硫平、齐拉西酮6种非典型抗精神病药物为首要怀疑药物的ADE共389431例次,涉及报告病例116706例。血液系统ADE报告共计47144例次,涉及报告病例9658例。氯氮平产生血液系统信号22个,涉及报告病例6808例;奥氮平产生血液系统信号19个,涉及报告病例736例;喹硫平产生血液系统信号18个,涉及报告病例560例;阿立哌唑产生血液系统信号8个,涉及报告病例60例;利培酮产生血液系统信号3个,涉及报告病例16例;齐拉西酮产生血液系统信号1个,涉及报告病例5例。结论 基于真实世界的非典型抗精神病药物血液系统ADE信号挖掘有助于开展安全性评价,为临床安全应用提供参考。     

A review of atypical antipsychotic drugs versus conventional medication in schizophrenia

Atypical antipsychotics are replacing conventional antipsychotics for the treatment of schizophrenia. They are considered to be at least as effective as conventional agents, with most producing fewer extrapyramidal symptoms. This review presents the evidence from published meta-analyses and describes differences in clinical effectiveness and tolerability between conventional and atypical antipsychotic agents. In addition, it discusses some of the more significant adverse effects including tardive dyskinesia, weight gain, diabetes and sudden death. Results from meta-analyses are conflicting, with some finding no significant advantages on measures of efficacy or tolerability for atypical antipsychotics over moderate daily doses of conventional drugs. Other results have shown that some atypical drugs have at least minor efficacy advantages over conventional comparators. Atypical antipsychotics exhibit a much reduced risk for tardive dyskinesia compared with conventional drugs. However, weight gain is more common with some atypical drugs (especially clozapine and olanzapine). Both conventional and atypical antipsychotics have been associated with diabetes, with most reports implicating both clozapine and olanzapine. Finally, atypical antipsychotics (unlike conventional drugs) have little or no effect on QT and are not associated with sudden death.     

Higher than Physician’s Desk Reference (US) doses on atypical antipsychotics

The Physician’s Desk Reference (PDR) was established to provide for the practicing of a complete listing of all medications with the FDA-approved labelling, including dosage recommendations. Perhaps in order to maximise individual usage of medications, pharmaceutical companies have frequently targeted lowest possible doses for FDA approval. However, many patients with a variety of illnesses due to resistance and/or multiple illnesses, may need higher than these dose ranges to maximise therapeutic response. In terms of regularly prescribed atypical antipsychotics released over the past 10 years, only risperidone initially obtained approval for a dose for psychosis (16 mg) higher than that suggested currently (maximum of 8 mg). The dose that was approved for mania was lower: a maximum of 6 mg. The others: respectfully, olanzapine (schizophrenia:15 mg, mania:20 mg), quetiapine (schizophrenia: 750 mg; mania: 800 mg), ziprasidone (schizophrenia and mania: 160 mg) and aripiprazole (schizophrenia and mania: 30 mg) obtained approvals for psychosis that may limit adverse events but, at the same time, limit benefits. Other data from various sources (double-blind trials, open-label trials, reviews and case reports) have found safety and/or efficacy for the following maximum doses: olanzapine (40 mg), quetiapine (1600 mg), ziprasidone (320 mg) and aripiprazole (75 mg). Reports above those doses are included, but either are insufficient in numbers or bring up questions on safety. In many situations, feared increase in adverse events were not magnified by use of higher doses.     

Weight gain and antipsychotics: a drug safety review

Introduction: Second-generation antipsychotics (SGAs) are widely used in several psychiatric disease entities and exert to a different extent a risk for antipsychotic-induced weight gain (AIWG). As AIWG is associated with an increase in metabolic syndrome or cardiovascular events, knowledge of these risks is crucial for further monitoring and the initiation of counteractive measures.

Areas covered: We searched PubMed and Web of Sciences for randomized-controlled trials and naturalistic observational studies published between 2010 and 2014 with sample sizes exceeding 100, including all marketed SGAs apart from zotepine, and providing data on weight increase. We also summarized relevant systematic reviews and meta-analyses of head-to-head comparisons.

Expert opinion: Recently published data still support the hierarchical ranking of SGAs already proposed in previous reviews ranking clozapine and olanzapine as having the highest risk, followed by amisulpride, asenapine, iloperidone, paliperidone, quetiapine, risperidone and sertindole in the middle, and aripiprazole, lurasidone and ziprasidone with the lowest risk. Number needed to harm varied considerably in our meta-analysis. Younger patients and patients with a lower baseline body mass index are most vulnerable. The greatest amount of weight gain occurs within the first weeks of treatment. AIWG occurs in all diagnostic groups and is also common in treatment with first-generation antipsychotics; therefore, awareness of this adverse event is essential for anyone prescribing antipsychotics.     

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。