Efficacy and adverse effects of atypical antipsychotics for dementia: Meta-analysis of randomized, placebo-controlled trials
Efficacy and adverse effects of atypical antipsychotics for dementia: Meta-analysis of randomized, placebo-controlled trials
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DOI：
10.1097/01.jgp.0000200589.01396.6d
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发表时间：
2006-03-01
影响因子：
7.2
通讯作者：
Insel, PS
中科院分区：
文献类型：
--
作者：
Schneider, LS;Dagerman, K;Insel, PS
目的：非典型抗精神病药物被广泛用于治疗阿尔茨海默病（AD）和其他痴呆症患者的妄想，攻击和激动。一些临床试验没有显示出有效性，并且人们对不良事件感到担忧。本研究的目的是评估药物治疗痴呆患者的疗效和不良事件的证据。方法：MEDLINE、科克伦对照试验登记、会议、报告和从申办者处获得的信息用于本研究。研究了在美国上市的非典型抗精神病药物在AD或痴呆患者中进行的已发表和未发表的随机、安慰剂对照、双盲、平行组试验。提取临床和试验特征、结局和不良事件。由第二名审查员检查数据。15项试验（包括16项非典型抗精神病药物与安慰剂对照）符合选择标准：阿立哌唑（k = 3）、奥氮平（k = 5）、奎替鲁（k = 3）和利培酮（k = 5）。共有3，353名患者随机接受药物治疗，1，757名患者接受安慰剂治疗。使用标准荟萃分析方法总结结果。结果：试验报告的质量各不相同。通过荟萃分析观察了阿立哌唑和利培酮在评定量表上的疗效，但未观察到奥氮平的疗效。答复率往往没有报告。对于不太严重的痴呆症患者、门诊患者和精神病患者，影响较小。大约三分之一的人退出，药物和安慰剂之间没有总体差异。不良事件主要是嗜睡和尿路感染或尿失禁，以及利培酮或奥氮平的锥体外系症状或步态异常。认知测试分数因药物而恶化。没有证据表明损伤、福尔斯或晕厥增加。有显著的脑血管事件风险，尤其是利培酮;其他地方报告了总体死亡风险增加。结论：症状评定量表上的小统计效应量支持阿立哌唑和利培酮疗效的证据。不完整的报告限制了缓解率和临床意义的估计。脱落和不良事件进一步限制了有效性。应在医疗需求和替代品的有效性和安全性的背景下考虑非典型药物。需要对个体患者进行荟萃分析，以更好地评估临床意义和有效性。
Objective: Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease ( AD) and other dementia. Several clinical trials have not shown efficacy, and there have been concerns about adverse events. The objective of this study was to assess the evidence for efficacy and adverse events of atypicals for people with dementia Methods: MEDLINE, the Cochrane Register of Controlled Trials, meetings, presentations, and information obtained from sponsors were used in this study. Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States were studied. Clinical and trials characteristics, outcomes, and adverse events were extracted. Data were checked by a second reviewer. Fifteen trials including 16 contrasts of atypical antipsychotics with placebo met selection criteria: aripiprazole (k = 3), olanzapine (k = 5), quetiapine (k = 3), and risperidone (k = 5). A total of 3,353 patients were randomized to drug and 1,757 to placebo. Standard meta-analysis methods were used to summarize outcomes. Results: Quality of the reporting of trials varied. Efficacy on rating scales was observed by meta-analysis for aripiprazole and risperidone, but not for olanzapine. Response rates were frequently not reported. There were smaller effects for less severe dementia, outpatients, and patients selected for psychosis. Approximately one-third dropped out without overall differences between drug and placebo. Adverse events were mainly somnolence and urinary tract infection or incontinence across drugs, and extrapyramidal symptoms or abnormal gait with risperidone or olanzapine. Cognitive test scores worsened with drugs. There was no evidence for increased injury, falls, or syncope. There was a significant risk for cerebrovascular events, especially with risperidone; increased risk for death overall was reported elsewhere. Conclusions: Small statistical effect sizes on symptom rating scales support the evidence for the efficacy of aripiprazole and risperidone. Incomplete reporting restricts estimates of response rates and clinical significance. Dropouts and adverse events further limit effectiveness. Atypicals should be considered within the context of medical need and the efficacy and safety of alternatives. Individual patient meta-analyses are needed to better assess clinical significance and effectiveness.