Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.
Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.
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DOI：
10.1186/s12877-018-0857-5
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发表时间：
2018-07-24
期刊：
影响因子：
4.1
通讯作者：
Castells X
中科院分区：
文献类型：
--
作者：
Blanco-Silvente L;Capellà D;Garre-Olmo J;Vilalta-Franch J;Castells X
美金刚治疗阿尔茨海默病（AD）的风险-效益关系仍不清楚。此外，还观察到临床试验结果之间的变异性。本研究的目的是调查美金刚治疗AD患者的风险-获益关系，并确定患者、干预和研究设计相关协变量的预测效应。对双盲、安慰剂对照临床试验进行了系统综述和荟萃分析。主要结局为全因停药、因不良事件（AE）停药和对认知功能的疗效。计算比值比（OR）和标准均数差（SMD）及其95%可信区间。进行荟萃回归以确定相关协变量。采用科克伦协作网评价纳入试验的偏倚风险。纳入了18项研究，涉及5004例患者。美金刚和安慰剂之间的全因治疗中止（OR = 0.97 [0.82，1.14]）和因AE中止（OR = 1.18 [0.91，1.53]）无差异。美金刚对认知功能的改善较小（SMD = 0.15 [0.08，0.22]）。基线功能能力与全因停药和因AE停药呈正相关。我们的研究表明，美金刚对AD的疗效很小，其安全性与安慰剂相似。没有证据表明美金刚胺可以改善治疗中断，表明存在可疑的风险-获益关系。没有干预特征或患者亚组明确显示出显著更好的风险-获益关系。CRD 42014015696。本文的在线版本（10.1186/s12877 - 018 - 0857 - 5）包含补充材料，可供授权用户使用。
The risk-benefit relationship of memantine treatment for Alzheimer’s disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates. A systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials. Eighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE. Our study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship. CRD42014015696. The online version of this article (10.1186/s12877-018-0857-5) contains supplementary material, which is available to authorized users.
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影响因子：
4
作者：
Di Santo, Simona Gabriella;Prinelli, Federica;Musicco, Massimo
通讯作者：
Musicco, Massimo
影响因子：
3.4
作者：
Cunill, R.;Castells, X.;Capella, D.
通讯作者：
Capella, D.
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
6
作者：
Castells, Xavier;Antoni Ramos-Quiroga, Josep;Casas, Miguel
通讯作者：
Casas, Miguel
影响因子：
4.8
作者：
FOLSTEIN, MF;FOLSTEIN, SE;MCHUGH, PR
通讯作者：
MCHUGH, PR