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。     

非典型抗精神病药治疗700例精神分裂症住院患者的应用分析

目的：了解我院精神分裂症住院患者非典型抗精神病药的应用现状,探讨临床使用非典型抗精神病药的特点。方法：随机抽查本院2008年住院的700例诊断为精神分裂症患者应用非典型抗精神病药,采用WHO药物统计合作中心设定的限定日剂量（DDD）计算我院非典型抗精神病药的用药频度（DDDs）、药物利用指数（DUI）及联合用药情况。结果：非典型抗精神病药的DDDs排序为：喹硫平、利培酮、氯氮平、阿立哌唑、齐拉西酮、奥氮平。单一药物治疗496例,占70.86%;二联或三联用药204例,占29.14%。DUI≤1。结论：我院非典型抗精神病药用药结构倾向合理。对于精神分裂症的临床治疗应以单一药物治疗为主。     

我院2013年707例住院患者抗精神病药应用现状分析

目的了解我院抗精神病药的使用现状,为临床合理用药提供依据。方法对我院2013年7月22日住院和新入院的精神病患者的用药情况进行分析。结果在707例患者中,使用1种抗精神病药治疗的患者有421例(59.97%),奥氮平位居首位(91例,12.87%),其余依次为喹硫平(64例,9.05%)、利培酮(58例,8.20%)、氯氮平(45例,6.37%);联合2种药物治疗的有207例(29.28%),以氯氮平+阿立哌唑、氯氮平+利培酮、奥氮平+利培酮多见。结论非典型抗精神病药占临床用药主导地位,两种抗精神病药物联合用药比例较2008年有所增加。     

8种不同非典型抗精神病药严重不良反应对比研究

目的研究8种不同非典型抗精神病药不良反应规律和特点,为临床安全合理用药提供参考。方法收集2015年1月至2019年4月浙江省上报的氯氮平、利培酮、奥氮平、喹硫平、氨磺必利、齐拉西酮、阿立哌唑和帕利哌酮导致的严重不良反应报告1497例,利用Excel软件进行统计并分析。结果非典型抗精神病药不良反应累及系统以肝胆系统损害和神经系统损害为主;不同药物呈现特有的不良反应,如帕利哌酮导致生殖系统损害、氯氮平导致胃肠系统损害、奥氮平导致血液系统损害、氨磺必利导致内分泌系统损害、阿立哌唑导致泌尿系统损害。结论各种非典型抗精神病药不良反应发生广泛,要加强不良反应监测,如定期随访肝功能和B超等。另外,应关注不同药物特有的不良反应,结合患者的基础疾病进行临床合理用药。     

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。     

非典型抗精神病药物不良反应的性别差异

常用的非典型抗精神病药物有:阿立哌唑、氯氮平、奥氮平、奎硫平、利培酮及齐拉西酮.非典型抗精神病药物的药代动力学和不良反应均有性别差异.女性的CYP1A2酶的活性较男性低,致氯氮平和奥氮平的血药浓度高于男性.利培酮引起女性高催乳素水平,导致女性骨质疏松和性功能障碍的发生率高于男性.研究表明,非典型抗精神病药物使女性代谢综合征的发生率明显高于男性.其中女性和男性肥胖症、高血压、三酰甘油血症及高密度脂蛋白降低的发生率分别为76.3%和35 5%,46.9%和47.2%,42.2%和50.7%,48.9%和63.3%;女性和男性高血糖[≥100 mg/dl(5.55 mmol/L)和≥110 mg/dl(6.10 mmol/L)]的发生率分别为30.0%和21.7%,24.2%和14.1%.非典型抗精神病药物引起心电图QTc间期延长及锥体外系症状女性较男性多见;其中某些药物对胎儿有不良影响.     

非典型抗精神病药物与体重增加

查阅国内外有关非典型抗精神病药物与体重增加的临床试验资料和文献,并进行整理、分析。结果发现,非典型抗精神病药物氯氮平、奥氮平、奎硫平、左替平、利培酮均不同程度地引起体重增加,而齐哌西酮对体重的影响较小;体重增加一般发生于用药6～12周。本文对非典型抗精神病药物致体重增加的药理学机制及药物的顺应性等问题进行介绍。     

精神分裂症患者住院期间精神药物使用情况分析

目的了解精神分裂症患者住院期间精神药物使用情况。方法采用自编量表通过我院病案室出院登记系统,对我院2010年1月至2010年12月出院的精神分裂症患者住院期间使用精神药物的品种、剂量及合并用药情况进行调查。结果全院精神科总住院人数1940人,调查登记精神分裂症1350人,占总住院人数的69.6%。单一服用抗精神病药物者980例(72.6%),按使用率顺序为氯氮平(25.9%)、利培酮(17.8%)、氯丙嗪(15.6%)、氟哌啶醇(4.4%)、奥氮平(4.4%)、奋乃静(2.96%)、舒必利(1.5%)。两种精神药物合并者为360例(26.6%)。其中以氯氮平、利培酮、奥氮平再合并其他一种抗精神病药为多见。按使用率顺序主要为氯氮平+舒必利、利培酮+氯氮平、利培酮+舒必利、氯氮平+氟哌啶醇、氯氮平+哌泊噻嗪、氯氮平合并癸氟奋乃静、奥氮平合并氟哌啶醇等。三种抗精神病药合用者10例。另外,合并安坦220例(16.3%);异丙嗪60例(4.4%);苯二氮卓类药150例(11.1%);心得安260例(19.3%)。60例(4.4%)合用抗抑郁剂。合并ECT者210例(15.6%)。结论住院精神分裂症的治疗以单一应用抗精神病药为主,非典型抗精神病药的应用逐年增加,且居首位。新型非典型抗精神病药如利培酮等药物的应用增多,已经被广大医生及患者所接受。     

2007—2011年盐城市第四人民医院抗精神病药应用分析

目的：了解2007—2011年我院抗精神病药使用情况,以促进临床合理用药。方法：采用回顾性分析法,对2007—2011年我院抗精神病药销售金额、用药频度（DDDs）和限定日费用（DDC）等进行统计、分析。结果：新型非典型抗精神病药的用量逐年上升,5年销售金额增长了2.84倍,DDDs上升了2.53倍;而典型抗精神病药及非典型抗精神病药氯氮平的用量则逐年下降,5年DDDs下降了33.00%。利培酮、阿立哌唑、喹硫平、奥氮平的销售金额及DDDs排序均居前列。2011年抗精神病药的平均DDC比2007年增长了2.26倍,DDC呈现快速增长趋势。结论：我院抗精神病药应用合理,新型非典型抗精神病药的用量呈现增长态势,典型抗精神病药及非典型抗精神病药氯氮平仍是部分患者特别是经济承受能力较低患者的首选药,选用国产和普通剂型的药物有利于降低药物治疗成本。     

非典型抗精神病药治疗精神分裂症的临床应用评价

目的:系统论述非典型抗精神病药治疗精神分裂症临床研究和应用的进展,评价其临床疗效和安全性.方法:通过互联网查阅Medline、Pubmed、Ovid、Science Direct、Proquest及国内外相关专业杂志所公开发表的研究报道进行综合评价和分析.结果与结论:非典型抗精神病药近10年来的临床应用研究进展迅速,除氯氮平外,大多数新型非典型抗精神病药如利培酮、奥氮平、喹硫平、齐拉西酮及阿立哌唑等已成为精神分裂症各种症状维度、不同病期和复发预防的一线临床选择,特别是在不良反应方面克服了经典抗精神病药和氯氮平的诸多严重缺点,同时,各种临床研究结果已被多项应用循证医学方法的系统研究所证实.     

Therapeutic drug monitoring of antipsychotics

Therapeutic drug monitoring of conventional and atypical antipsychotics offers numerous clinical advantages to the clinician. These include cost savings, decreased risk of toxicity, and improved compliance. Among these drugs, studies of haloperidol, olanzapine, and clozapine have provided the most compelling data to justify therapeutic drug monitoring. Among atypical antipsychotics, although data document the utility of routine monitoring of clozapine and olanzapine blood levels, there are no similar data available for either risperidone or quetiapine. Additionally, the utility of therapeutic drug monitoring is enhanced by the availability of prospective dosing schemes for haloperidol, olanzapine, and clozapine.     

Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder

The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.     

Glucose intolerance with atypical antipsychotics.

BACKGROUND: Previous studies have suggested that the atypical antipsychotics clozapine and olanzapine may be associated with an increased risk of glucose intolerance and diabetes mellitus. Early studies have also suggested an association between use of conventional antipsychotics and the development of glucose intolerance. OBJECTIVE: To examine quantitatively the association between glucose intolerance including diabetes mellitus and the use of the atypical antipsychotics clozapine, olanzapine or risperidone, and to identify possible risk factors for the development of glucose intolerance during treatment with these drugs. METHODS: All reports suggestive of glucose intolerance for clozapine, olanzapine and risperidone were identified in the WHO database for adverse drug reactions. In the analyses of possible risk factors for glucose intolerance all other reports of adverse drug reactions for clozapine, olanzapine and risperidone were used as reference. Using the Bayesian Confidence Propagation Neural Network method, the strengths of the associations over time between glucose intolerance and the use of these drugs were analysed. For comparison, the strengths of the associations between glucose intolerance and the use of the conventional antipsychotics haloperidol and chlorpromazine were also analysed. RESULTS: Clozapine, olanzapine and risperidone were significantly associated with glucose intolerance. In contrast, chlorpromazine and haloperidol were not associated with glucose intolerance. For clozapine, olanzapine and risperidone grouped together, the following potential risk factors for glucose intolerance were identified: an underlying diabetic condition (odds ratio [OR] 10.22, 95% CI 8.20-12.73), an increase in weight (OR 2.36, 95% CI 1.76-3.17), male gender (OR 1.27, 95% CI 1.11-1.47), and concomitant use of valproic acid (OR 1.97, 95% CI 1.61-2.40), selective serotonin reuptake inhibitors (OR 1.63, 95% CI 1.33-1.99) or buspirone (OR 2.24, 95% CI 1.33-3.77). CONCLUSION: Treatment with clozapine, olanzapine or risperidone appears to be associated with an increased risk of glucose intolerance.     

Clozapine discrimination with a low training dose distinguishes atypical from typical antipsychotic drugs in rats

Rationale: Previous drug discrimination studies with clozapine have not reliably distinguished between atypical and typical antipsychotics. Objectives: The present study was conducted to determine whether low-dose clozapine drug discrimination could distinguish atypical from typical antipsychotics. Methods: Rats were trained to discriminate 1.25 mg/kg clozapine from vehicle in a two-lever drug discrimination procedure. Results: Generalization testing revealed full substitution with the atypical antipsychotics olanzapine (90.3% maximum generalization), sertindole (99.8%), and risperidone (87.1%) and partial substitution for quetiapine (seroquel, 66.4%) and the typical antipsychotics haloperidol (56.8%) and thioridazine (74.3%). Remoxipride (23.1%) and the typical antipsychotics chlorpromazine (27.9%) and fluphenazine (29.5%) did not reliably substitute for clozapine. Conclusions: In contrast to previous clozapine drug discrimination studies with higher training doses, the atypical antipsychotics olanzapine, sertindole, and risperidone reliably substituted for clozapine while typical antipsychotics did not. These results suggest that low-dose clozapine drug discrimination may be a more sensitive assay for distinguishing atypical from typical antipsychotic drugs. Received: 3 August 1999 / Final version: 9 December 1999     

Lack of a pharmacokinetic interaction between mirtazapine and the newer antipsychotics clozapine, risperidone and olanzapine in patients with chronic schizophrenia.

The effect of mirtazapine on steady-state plasma concentrations of the newer atypical antipsychotics clozapine, risperidone and olanzapine was investigated in 24 patients with chronic schizophrenia. In order to treat residual negative symptoms, additional mirtazapine (30 mg per day) was administered for six consecutive weeks to nine patients stabilized on clozapine therapy (200-650 mg per day), eight on risperidone (3-8 mg per day) and seven on olanzapine (10-20mg per day). There were only minimal and statistically insignificant changes in mean plasma concentrations of clozapine and its metabolite norclozapine, risperidone and its metabolite 9-hydroxyrisperidone, and olanzapine during the study period. Mirtazapine co-administration with either clozapine, risperidone or olanzapine was well tolerated. In the overall sample, a slight improvement in negative symptomatology, as assessed by the Scale for Assessment of Negative Symptoms, was observed at final evaluation (P<0.01) and six patients (two in each treatment group) were classified as responders. While double-blind, controlled studies are needed to evaluate the potential clinical benefits of mirtazapine in chronic schizophrenia, our findings indicate that mirtazapine has a negligible effect on the metabolism of clozapine, risperidone and olanzapine and can be added safely to an existing treatment with these antipsychotics.     

Antipsychotic-induced type 2 diabetes: evidence from a large health plan database

Case evidence suggests that some of the atypical antipsychotics may induce type 2 diabetes. The objective of this study was to evaluate the association of antipsychotic treatment with type 2 diabetes in a large health plan database. Claims data for patients with psychosis within a health plan of nearly 2 million members were analyzed using logistic regression. Frequencies of newly treated type 2 diabetes in patients untreated with antipsychotics and among patients treated with quetiapine, risperidone, olanzapine, and conventional antipsychotics were compared. Based on exposure measured in months of antipsychotic treatment, quetiapine and risperidone patients had estimated odds of receiving treatment for type 2 diabetes that were lower than those of patients untreated with antipsychotics (not statistically significant); patients treated with conventional antipsychotics had estimated odds that were virtually equivalent to those of patients untreated with antipsychotics; olanzapine alone had odds that were significantly greater than those of patients untreated with antipsychotics (P = 0.0247). Odds ratios based on 8 months of screening for pre-existing type 2 diabetes and assuming 12 months of antipsychotic treatment were: risperidone = 0.660 (95% CI 0.311-1.408); olanzapine = 1.426 (95% CI 1.046-1.955); quetiapine = 0.976 (95% CI 0.422-2.271); and conventional antipsychotics = 1.049 (95% CI 0.688-1.613). Case reports, prospective trials, and other retrospective studies have increasingly implicated olanzapine and clozapine as causing or exacerbating type 2 diabetes. Few have implicated risperidone while evidence on quetiapine has been limited. This study supports earlier findings on risperidone versus olanzapine and builds evidence on quetiapine. Additional studies are needed to evaluate the association of antipsychotic treatment with type 2 diabetes.     

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。