Schneider Lon S, Dagerman Karen, Insel Philip S
Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, USA.
Am J Geriatr Psychiatry. 2006 Mar;14(3):191-210. doi: 10.1097/01.JGP.0000200589.01396.6d.
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.
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 Published and unpublished randomized, placebo-controlled, double-blind, parallel-group trials in patients with AD or dementia of atypical antipsychotics marketed in the United States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.
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.
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.
非典型抗精神病药物被广泛用于治疗阿尔茨海默病（AD）及其他痴呆患者的妄想、攻击行为和激越症状。多项临床试验未显示出其有效性，且人们对不良事件也存在担忧。本研究的目的是评估非典型抗精神病药物对痴呆患者有效性和不良事件的证据。
本研究使用了MEDLINE、Cochrane对照试验注册库、会议、报告以及从赞助商处获得的信息。对美国已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、平行组试验进行了研究。提取了临床和试验特征、结果及不良事件。数据由第二位审阅者进行核对。15项试验（包括16项非典型抗精神病药物与安慰剂的对比）符合入选标准：阿立哌唑（k = 3）、奥氮平（k = 5）、喹硫平（k = 3）和利培酮（k = 5）。共有3353例患者被随机分配至药物组，1757例被分配至安慰剂组。采用标准的荟萃分析方法汇总结果。
试验报告的质量参差不齐。荟萃分析观察到阿立哌唑和利培酮在评分量表上有疗效，但奥氮平没有。缓解率常常未被报告。对于病情较轻的痴呆患者、门诊患者以及因精神病入选的患者，疗效较小。约三分之一的患者退出试验，药物组和安慰剂组之间无总体差异。不良事件主要包括所有药物共有的嗜睡、尿路感染或尿失禁，以及利培酮或奥氮平导致的锥体外系症状或异常步态。药物会使认知测试分数恶化。没有证据表明损伤、跌倒或晕厥增加。存在脑血管事件的显著风险，尤其是利培酮；其他地方报告了总体死亡风险增加。
症状评分量表上较小的统计学效应量支持了阿立哌唑和利培酮有效性的证据。报告不完整限制了对缓解率和临床意义的评估。退出试验和不良事件进一步限制了有效性。应在医疗需求以及替代药物的有效性和安全性背景下考虑使用非典型抗精神病药物。需要进行个体患者荟萃分析以更好地评估临床意义和有效性。
