不同非典型抗精神病药严重不良反应监测及对策分析

目的 探讨不同非典型抗精神病药的严重不良反应监测结果及防范对策。方法 回顾分析十堰市中西医结合医院精神科2017年1月至2019年12月接收的行非典型抗精神病药治疗且发生严重不良反应1277例患者的临床资料,统计患者性别、年龄、各药物不良反应占比。结果 奥氮平不良反应占比30.15%最高,依次为喹硫平、利培酮、氯氮平、阿立哌唑、帕利哌酮、氨磺必利、齐拉西酮。新的严重不良反应氯氮平19.61%占比最高;21～40岁不良反应占比58.73%最高;非典型抗精神病药不良反应累及系统及器官以肝胆系统损害29.13%占比最高。1277例患者不良反应好转1275例,后遗症肥胖1例,死亡1例。结论 非典型抗精神病药治疗中易出现严重不良反应,对各个系统器官均造成损害,需加强对患者的用药监测及指导。     

2019—2022年漯河市中心医院西城分院抗精神病药的使用情况分析

目的 分析漯河市中心医院西城分院2019—2022年抗精神病药物的用药情况,为临床合理用药提供参考。方法 采用回顾性研究方法,对漯河市中心医院西城分院2019—2022年抗精神病药物的销售金额、用药频度（DDDs）、排序比（B/A）和日均费用（DDC）进行统计分析。结果 抗精神病药物的销售金额先增长后下降,非典型抗精神病药物销售金额占比始终较高;DDDs呈逐年上涨趋势,阿立哌唑和奥氮平一直占据销售金额和DDDs的前2位;DDC值变化较大,奥氮平、氨磺必利等高价品种的DDC值下降明显,而一些低价品种DDC则略有上涨;氨磺必利、奥氮平和阿立哌唑的B/A值变动较大,2022年所有抗精神病药物B/A值均接近1。结论 该院抗精神病药的使用情况较为合理,临床治疗以疗效好、不良反应少的非典型抗精神病药为主,特别是阿立哌唑和奥氮平,使用频度最高。氨磺必利和喹硫平用药频度增幅明显。     

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。     

新型抗精神病药帕利哌酮缓释片的临床研究进展

帕利哌酮缓释(paliperidone ER)片是于2009年在国内上市的一种新型抗精神病药物。本文比较了帕利哌酮与利培酮在药理学特性和作用机制方面的区别,对帕利哌酮与其他非典型抗精神病类药物如利培酮、喹硫平、奥氮平、阿立哌唑在临床应用以及不良反应等方面的对照研究进展进行了综述。     

2020—2022年青岛市精神卫生中心抗精神病药使用情况分析

目的 统计青岛市精神卫生中心2020—2022年抗精神病药使用情况并分析变化趋势,为临床合理用药提供参考。方法 采用回顾性分析方法统计青岛市精神卫生中心信息系统中2020年1月—2022年12月抗精神病药的销售金额,并计算用药频度（DDDs）、限定日费用（DDC）以及药品排序比（B/A）。结果 2020—2022年,青岛市精神卫生中心抗精神病药年销售金额基本稳定,奥氮平、喹硫平的销售金额及排序始终居于前2位;抗精神病药的DDDs呈现逐年增长的趋势,奥氮平DDDs基本稳定,始终居于第1位,喹硫平DDDs逐年增长,居于第2位;抗精神病药的DDC及排序基本稳定,帕利哌酮、氨磺必利、齐拉西酮、喹硫平的DDC排序始终居于前4位;阿立哌唑、氨磺必利、奥氮平、奋乃静、氟哌啶醇、喹硫平、硫必利、氯丙嗪、齐拉西酮、五氟利多的B/A值接近于1.00。结论 青岛市精神卫生中心抗精神病药的使用基本合理,后期仍需加强监督管理,以保证患者合理用药。     

探讨分析阿立哌唑、氨磺必利与奥氮平对精神分裂症患者阴性症状及糖脂代谢的影响

目的：观察并分析阿立哌唑、氨磺必利与奥氮平对精神分裂症患者阴性症状及糖脂代谢的影响。方法：将我院(2020年01月—2022年12月)收治的精神分裂症患者69例采用随机数字表法分成三组,各23例,以阿立哌唑治疗设为阿立哌唑组,以氨磺必利治疗设为氨磺必利组,以奥氮平治疗者设为奥氮平组。比较三组患者在治疗前、后的疾病严重程度综合征量表评分及糖脂代谢指标,评价治疗效果及用药后不良反应发生情况。结果：在治疗后三组患者均较治疗前疾病严重程度综合征量表评分降低(P<0.05),治疗后三组间疾病严重程度综合征量表评分相比,无统计学差异(P>0.05)。治疗4周后,阿立哌唑组与氨磺必利组患者HDL-C及LDL-C水平比较,无统计学差异(P>0.05)。阿立哌唑组患者FBG、TG、TC水平低于氨磺必利组、奥氮平组(P<0.05);阿立哌唑组患者HDL-C水平高于奥氮平组,LDL-C低于奥氮平组(P<0.05)。结论：阿立哌唑、氨磺必利与奥氮平治疗精神分裂症,均可以获得改善患者阴性症状严重程度,达到理想的治疗效果且用药安全性尚可。而阿立哌唑相较于氨磺必利与奥氮平,对于患者的糖...     

非典型抗精神病药的体内代谢与药物相互作用

典型抗精神病药物,又称第1代抗精神病药,代表药物有氯丙嗪、奋乃静、氟奋乃静、三氟拉嗪、氟哌啶醇、硫利达嗪等,由于它们不良反应多[1],如代谢综合征、高泌乳素血症、QTc延长、锥体外系不良反应大及体重增加等,现已逐渐被非典型抗精神病药物(即第2代抗精神病药物)取代.Leucht S等[2]对第1代抗精神病药和第2代抗精神病药进行了meta分析,认为从整体作用上讲,氯氮平、利培酮、奥氮平、氨磺必利4种药物要优于第1代抗精神病药和其他第2代抗精神病药物.本文在回顾大样本文献的基础上,从药物代谢酶和P-gp两方面对氯氮平、利培酮、奥氮平、氨磺必利的药物相互作用进行综述.     

非典型抗精神病药不良反应的回顾性调查

目的：通过对2005年至2008年我中心收集到与非典型抗精神病药有关的药品不良反应／事件报告表进行统计分析,包括氯氮平、利培酮、奥氮平、阿立哌唑四个品种,了解非典型抗精神病药不良反应发生情况,为临床合理用药提供参考。方法：采用回顾性分析方法对我中心2005年至2008年收到来自江西省医疗机构、药品生产经营企业及个人上报的因使用氯氮平、利培酮、奥氮平、阿立哌唑有关的药品不良反应／事件报告表,经分析评价后,向国家药品不良反应监测中心上报的523份ADR病例报告。结果：在523份不良反应病例报告中氯氮平272例,利培酮214例,阿立哌唑31例,奥氮平6例,新的一般病例28份,占5．35％;严重病例3份,占0．57％。不良反应主要表现为锥体外系病、心动过速、便秘、肝功能异常、白细胞减少、流涎、嗜睡等。不良反应结果大多好转或治愈,有后遗症病例,无死亡病例。结论：检索到的不良反应表现多为已知的不良反应,因此更要警惕及预防非典型抗精神病药物不良反应的发生。     

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。     

非典型抗精神病药致比萨综合征文献分析

目的： 了解非典型抗精神病药致比萨综合征临床特点、治疗及转归,为安全用药提供参考。方法： 检索国内外数据库中非典型抗精神病药致比萨综合征的报道,对其临床特点进行汇总与分析。结果： 共纳入文献病例36例,涉及利培酮、氯氮平、奥氮平、喹硫平、阿立哌唑、齐拉西酮、氨磺必利、帕利哌酮8个药物品种。其中,利培酮、氯氮平、奥氮平致比萨综合征较多,分别为8,8,5例次。病例中男16例,女20例;平均年龄（38.72±18.21）岁;15例（41.66%）患者比萨综合征发生在服药后30 d内,6例（16.67%）发生在服药数年后;躯干倾斜方向19例发生在右侧,15例发生在左侧,2例未明确倾斜方向;发生比萨综合征后27例停药、6例减量、3例对症治疗,症状在2 d~2个月内均缓解或消失;药物性比萨综合征关联性评价结果显示,肯定有关的3例,很可能有关的27例,可能有关的6例。结论： 非典型抗精神病药治疗过程均可能发生比萨综合征,且与多种因素相关,临床应用时需加强监测,以减少不良反应。     

274例氯氮平片致不良反应病例分析

目的分析274例氯氮平片致不良反应病例报告,探讨氯氮平片致不良反应的特点和规律,为临床安全合理用药提供参考。方法结合文献资料回顾分析274例氯氮平片致不良反应,尤其是严重不良反应进行综合分析。结果氯氮平片致不良反应涉及13个器官-系统损害,主要严重不良反应为以肝功能异常为主要表现的肝胆系统损害、以白细胞减少、粒细胞减少为主要表现的白细胞和网状内皮系统异常等。结论应关注氯氮平所致的严重不良反应,加强用药过程监护,减少药品带来的伤害。     

Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions

The involvement of cytochrome P450 (CYP) enzymes in the metabolism of the atypical (second-generation) antipsychotics clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and amisulpride is reviewed, and the possible relevance of this metabolism to drug-drug interactions is discussed. Clozapine is metabolized primarily by CYP1A2, with additional contributions by CYP2C19, CYP2D6 and CYP3A4. Risperidone is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4; the 9-hydroxy metabolite of risperidone (paliperidone) is now marketed as an antipsychotic in its own right. Olanzapine is metabolized primarily by direct glucuronidation and CYP1A2 and to a lesser extent by CYP2D6 and CYP3A4. Quetiapine is metabolized by CYP3A4, as is ziprasidone, although in the latter case aldehyde oxidase is the enzyme responsible for most of the metabolism. CYP2D6 and CYP3A4 are important in the metabolism of aripiprazole, and CYP-catalyzed metabolism of paliperidone and amisulpride appears to be minor. At the usual clinical doses, these drugs appear to not generally affect markedly the metabolism of other coadministered medications. However, as indicated above, several of atypical antipsychotics are metabolized by CYP enzymes, and physicians should be aware of coadministered drugs that may inhibit or induce these CYP enzymes; examples of such possible interactions are presented in this review.     

Atypical antipsychotic drugs: current issues of safety and efficacy in the management of schizophrenia

This review focuses on the comparative safety and efficacy profile of nine atypical antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine), which may ultimately affect the therapeutic options available for patients with schizophrenia. These antipsychotic compounds differ markedly in their potential to impact a number of quality-of-life measures. Furthermore, their differential effects on anxiety disorders, treatment-resistant depressive illness, cognitive functions and manic disorders may influence the selection of atypical antipsychotics for conditions associated with schizophrenia. The possible relevance of these parameters in evaluating the risk/benefit equation and probable involvement of varying receptor mechanisms is also discussed.     

Effect of antipsychotics on succinate dehydrogenase and cytochrome oxidase activities in rat brain

Typical and atypical antipsychotic drugs have been shown to have different clinical, biochemical, and behavioral profiles. It is well described that impairment of metabolism, especially in the mitochondria, leads to oxidative stress and neuronal death and has been implicated in the pathogenesis of a number of diseases in the brain. Considering that some effects of chronic use of antipsychotic drugs are still not well known and that succinate dehydrogenase (SDH) and cytochrome oxidase (COX) are crucial enzymes of mitochondria, in this work, we evaluated the activities of these enzymes in rat brain after haloperidol, clozapine, olanzapine, or aripiprazole chronic administration. Adult male Wistar rats received daily injections of haloperidol (1.5 mg/kg), clozapine (25 mg/kg), olanzapine (2.5, 5, or 10 mg/kg), or aripiprazole (2, 10 or 20 mg/kg) for 28 days. We verified that COX was not altered by any drug tested. Moreover, our results demonstrated that the atypical antipsychotic olanzapine inhibited SDH in the cerebellum and aripiprazole increased the enzyme in the prefrontal cortex. We also observed that haloperidol inhibited SDH in the striatum and hippocampus, whereas clozapine inhibited the enzyme only in the striatum. These results showed that antipsychotic drugs altered SDH activity but not COX. In this context, haloperidol, olanzapine, and clozapine may impair energy metabolism in some brain areas.     

Side effects of atypical antipsychotic drugs

Recently there has been increased concern over the side effects of the atypical antipsychotic drugs, including diabetes, hyperlipidemia and obesity. The relationship between diabetes and antipsychotic drugs requires a careful analysis. Patients with schizophrenia are known to suffer from diabetes more often than the general population. In addition, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs produce diabetes. Clozapine and olanzapine, in particular, have been implicated producing diabetes as well as diabetic ketoacidosis. Epidemiological surveys have supplemented the case reports, finding increased incidence of diabetes in patients treated with atypical antipsychotic agents, but these surveys have not yielded consistent results regarding the differential effects of the various atypical antipsychotic drugs. The mechanism by which antipsychotic agents produce diabetes is not elucidated. Weight gain and consequent alteration in triglycerides and cholesterol have been known to occur frequently with olanzapine and clozapine. The ensuing metabolic syndrome itself may cause insulin resistance and diabetes. In the absence of definitive scientific data on the differential effects of antipsychotic drugs in inducing diabetes, clinical prudence and careful monitoring of all patients on atypical antipsychotic drugs is necessary. Aripiprazole and ziprasidone have not been shown to increase weight or produce diabetes, but more information on the diabetogenic effects of ziprasidone and aripiprazole is needed. In order to assess the differential effects of atypical antipsychotic drugs in producing diabetes and the mechanisms by which they produce this reaction, further research is necessary.     

Novel antipsychotic agents: recent advances in the drug treatment of schizophrenia

Several new potential antipsychotic agents have been disclosed in the patent literature over the last 3 years and a sizeable number of drugs are actually in advanced stages of investigation. The majority of these cases involve compounds characterised by a high affinity for dopamine or 5-HT_2A receptors, associated or not to low dopamine receptor affinity or by affinity for other serotonin receptors such as 5-HT₆ and 5-HT₇, which may indirectly modulate mesolimbic dopaminergic neurons, producing efficacy against positive and negative symptoms of schizophrenia. Other patents have focused on chemical entities capable of relieving schizophrenic symptoms by interaction with less obvious receptors, such as glutamate or sigma receptors. A few patents claim the development of atypical antipsychotic drugs, structurally related to olanzapine and aripiprazole, characterised by high efficacy and low propensity to induce motor disturbances and blood disorders. Starting from the typical antipsychotics, taking into account the challenging pharmacological profile of clozapine, olanzapine and aripiprazole, this update will focus on the recent and ongoing activity in the development of novel antipsychotic drugs.     

Discriminative stimulus properties of N-desmethylclozapine, the major active metabolite of the atypical antipsychotic clozapine, in C57BL/6 mice

N-desmethylclozapine (NDMC) is the major active metabolite of the atypical antipsychotic drug clozapine and may contribute to the therapeutic efficacy of clozapine. Although they share many pharmacological features, it is noteworthy that NDMC is a partial dopamine D2 and cholinergic muscarinic M1/M4 agonist, whereas clozapine is a weak dopamine D2 receptor inverse agonist/antagonist and a nonselective muscarinic antagonist. To better understand the in-vivo pharmacological mechanisms of these drugs, male C57BL/6NHsd-wild-type mice were trained to discriminate 10.0 mg/kg NDMC from vehicle in a two-lever drug discrimination procedure for food reward. It was found that the parent drug clozapine fully substituted for NDMC, whereas the typical antipsychotic drug haloperidol (dopamine D2 antagonist) and the atypical antipsychotic drug aripiprazole (D2 partial agonist) did not substitute for NDMC. These results demonstrated that clozapine and its major metabolite NDMC share in-vivo behavioral properties (i.e. discriminative stimulus properties) that are likely due to shared pharmacological mechanisms that differ from other antipsychotic drugs. The discriminative stimulus properties of NDMC probably reflect a compound cue similar to that of its parent drug clozapine due to its diverse binding profile.     

我院2010年至2012年抗精神病药应用分析

目的评价医院抗精神病药应用情况,为临床合理、经济用药提供参考。方法采用世界卫生组织（WHO）推荐的限定日剂量分析法,对医院2010年至2012年抗精神病药使用金额、用药频度（DDDs）及日均费用（DDC）进行统计和分析。结果医院抗精神病药销售金额和DDDs逐年增加,其中非典型抗精神病药销售金额和DDDs增长迅速,阿立哌唑和齐拉西酮新型非典型抗精神病药增长尤其快,典型抗精神病药销售金额增长乏力,DDDs呈下降趋势。结论疗效好、不良反应小的非典型抗精神病药有逐渐取代典型抗精神病药的趋势,阿立哌唑、齐拉西酮等新型非典型抗精神病药应用前景广阔。     

我院442例药品不良反应报告分析

目的:探讨我院药品不良反应(ADR)发生的特点及规律,为临床合理用药及药品安全性评价提供参考。方法:对我院2009-2010年收集到的442例有效ADR报告进行统计、分析。结果:442例ADR报告中,涉及药品159种,60岁以上患者发生ADR的比例最高(138例,占31.22%);静脉注射给药引发的ADR最多(349例,占78.96%);最易引起ADR的药物为抗感染药(209例,占47.29%),其次为中药制剂(64例,14.48%);ADR损害类型主要以皮肤及其附件损害为主(223例,占50.45%),其次为消化系统和心血管系统损害;新的ADR11例,以中药制剂引发的为主;严重ADR32例,以过敏性休克较多(7例,占严重ADR病例的21.88%),其次为肝功能异常和高热。结论:临床应重视和加强ADR监测,合理用药,减少或避免ADR的发生。