The Efficacy and Safety of Atypical Antipsychotics for the Treatment of Dementia: A Meta-Analysis of Randomized Placebo-Controlled Trials
The Efficacy and Safety of Atypical Antipsychotics for the Treatment of Dementia: A Meta-Analysis of Randomized Placebo-Controlled Trials
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DOI：
10.3233/jad-140579
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Zhu, Gang
中科院分区：
文献类型：
--
作者：
Ma, Hui;Huang, Yinglin;Zhu, Gang
背景资料：非典型抗精神病药（SGAs）用于治疗痴呆的精神和行为症状存在争议，其疗效可能被不良事件（AE）抵消。目的：评价SGAs治疗痴呆的精神和行为症状的有效性、安全性和耐受性。两名研究人员独立检索了MEDLINE、PsychINFO和科克伦对照试验中心登记册，截至2013年6月的随机对照试验（DB-PC-RCT），以英文撰写。使用简明精神病评定量表（BPRS）、Cohen-Mansfield激越量表（CMAI）、神经精神量表（NPI）、临床疗效总评量表（CGI-C）和（或）临床疗效总评量表（CGI-S）测量疗效。通过脱落、AE和死亡的频率测量安全性和耐受性。共纳入了16项DB-PC-RCT中的19项治疗比较，其中3，343名患者随机分配至抗精神病药组，1，707名患者随机分配至安慰剂组。这项荟萃分析表明，非典型抗精神病药物对BPRS有显著疗效（MD =-1.58，95%CI = -2.52 - -0.65），CMAI（-1.84，-3.01 - -0.61），NPI（-2.81，-4.35 - -1.28），CGI-C（-0.32，-0.44 - -0.20）和CGI-S（-0.19，-0.30 - -0.09）与安慰剂相比（所有p < 0.01）。接受非典型抗精神病药物治疗的患者停药风险无差异（p > 0.05），风险显著增加嗜睡（所有患者p < 0.05）（OR = 2.95），锥体外系症状（1.74），脑血管AE（2.50）、尿路感染（1.35），水肿（1.80），步态异常（3.35）死亡（1.52），以及较低的躁动风险结论：非典型抗精神病药物治疗痴呆的疗效可能与其不良事件发生率和死亡率的增加相抵消。因此，应根据临床需要仔细考虑疗效、安全性和耐受性。
Background: The application of atypical antipsychotics (SGAs) for treatment of psychiatric and behavioral symptoms of dementia is controversial since their efficacy might be offset by their adverse events (AEs).Objective: To assess the efficacy, safety, and tolerability of SGAs for treatment of psychological and behavioral symptoms of dementia.Methods: Two researchers searched MEDLINE, PsychINFO, and the Cochrane Central Register of Controlled Trials independently for double-blind, placebo-controlled, randomized controlled trials (DB-PC-RCTs) as of June 2013, written in English. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), Clinical Global Impression of Change (CGI-C), and (or) Clinical Global Impression of Severity (CGI-S). Safety and tolerability were measured by frequencies of drop-outs, AEs, and death. In total, 19 treatment comparisons drawn from 16 DB-PC-RCTs were included, and 3,343 patients randomized to the antipsychotic group and 1,707 to the placebo group were assessed.Results: This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on BPRS (MD = -1.58, 95% CI = -2.52 - -0.65), CMAI (-1.84, -3.01 - -0.61), NPI (-2.81, -4.35 - -1.28), CGI-C (-0.32, -0.44 - -0.20), and CGI-S (-0.19, -0.30 - -0.09), compared to placebo (p < 0.01 for all). Patients receiving atypical antipsychotics showed no difference in risk for discontinuation (p > 0.05), significantly higher risks (p < 0.05 for all) for somnolence (OR = 2.95), extrapyramidal symptoms (1.74), cerebrovascular AEs (2.50), urinary tract infection (1.35), edema (1.80), gait abnormality (3.35), and death (1.52), and a lower risk for agitation (OR = 0.80, p = 0.03).Conclusions: The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.