School of Pharmacy, Monash University Malaysia, Selangor, Malaysia.
Clinical Trials and Evidence Base Syntheses Research Unit (CTEBs RU), Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand.
Br J Clin Pharmacol. 2018 Jul;84(7):1445-1456. doi: 10.1111/bcp.13604. Epub 2018 May 14.
To determine the most efficacious and acceptable treatments of agitation in dementia.
MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks.
Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses.
Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.
确定治疗痴呆症激越最有效和最可接受的方法。
检索 MEDLINE、EMBASE、PsycINFO、CENTRAL 和 clinicaltrials.gov，检索时间截至 2017 年 2 月 7 日。两位独立评审员选择了缓解各种类型痴呆患者激越的治疗方法的随机对照试验（RCT）。使用标准化表格提取数据，并使用修订后的 Cochrane RCT 偏倚风险工具评估研究质量。使用荟萃分析汇总数据。主要结局是 8 周时的疗效，定义为基线激越评分降低 50%的应答率。次要结局是治疗的可接受性，定义为 8 周时的治疗持续时间。
共纳入 36 项 RCT 研究，包含 5585 名参与者（30.9%为男性；平均±标准差年龄 81.8±4.9 岁）。右美沙芬/奎尼丁（比值比 3.04；95%置信区间 1.63-5.66）、利培酮（比值比 1.96；95%置信区间 1.49-2.59）和选择性 5-羟色胺再摄取抑制剂类（比值比 1.61；95%置信区间 1.02-2.53）均明显优于安慰剂。氟哌啶醇的疗效似乎不及几乎所有的对照药物。除奥卡西平外，大多数治疗方法的治疗持续时间与安慰剂相比均无差异，但奥卡西平的治疗持续时间更短。亚组和敏感性分析结果支持这些发现。
利培酮、5-羟色胺再摄取抑制剂类和右美沙芬/奎尼丁为痴呆症激越提供了疗效证据，尽管右美沙芬/奎尼丁的证据仅基于一项 RCT。由于缺乏疗效，我们不支持处方氟哌啶醇，由于缺乏可接受性，也不支持处方奥卡西平。处方决策应基于对益处和风险的全面考虑，包括本荟萃分析未评估的风险。
