Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials
Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials
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DOI：
10.1136/bmj.331.7512.321
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发表时间：
2005-08-06
影响因子：
105.7
通讯作者：
van den Bussche, H
中科院分区：
文献类型：
--
作者：
Kaduszkiewicz, H;Zimmermann, T;van den Bussche, H
目的阿尔茨海默病的药物治疗主要集中在用胆碱酯酶抑制剂纠正中枢神经系统胆碱能缺乏。目前推荐三种胆碱酯酶抑制剂：多奈哌齐、卡巴拉汀和加兰他敏。本综述评估了推荐这些药物的科学证据。数据来源检索Medline中的“多奈哌齐”、“卡巴拉汀”和“加兰他敏”，受限于“随机对照试验”。（1989年至2004年11月），Embase（1989- 2004年11月）和科克伦系统评价数据库（不受语言限制）。纳入了基于临床结果检查疗效的随机对照试验，其中将多奈哌齐、卡巴拉汀或加兰他敏治疗与安慰剂治疗阿尔茨海默病患者进行了比较。每个研究进行了独立评估，按照预定义的检查表的标准的方法学quality.Results 22个试验符合纳入标准。随访时间为6周至3年。通过70分阿尔茨海默病评估量表-认知子量表测量认知结果的14项研究中有12项显示出1.5分至3.9分的差异，有利于各自的胆碱酯酶抑制剂。所有12项试验都报告了受益，这些试验使用了基于临床医生访谈的变化印象量表，并提供了护理人员的输入。所有研究的方法评估发现相当大的问题，例如，多重测试没有纠正的多重性或排除患者后randomisation.Conclusion由于有缺陷的方法和小的临床效益，胆碱酯酶抑制剂治疗阿尔茨海默病的建议的科学依据是值得怀疑的。
Objectives Pharmacological treatment of Alzheimer's disease focuses on correcting the cholinergic deficiency in the central nervous system with cholinesterase inhibitors. Three cholinesterase inhibitors are currently recommended: donepezil, rivastigmine, and galantamine. This review assessed the scientific evidence for the recommendation of these agents.Data sources The terms "donepezil", "rivastigmine", and "galantamine", limited by "randomized-controlled-trials" were searched in Medline (1989-November 2004), Embase (1989-November 2004), and the Cochrane Database of Systematic Reviews without restriction for language.Study selection All published, double blind, randomised controlled trials examining efficacy on the basis of clinical outcomes, in which treatment with donepezil, rivastigmine, or galantamine was compared with placebo in patients with Alzheimer's disease, were included. Each study was assessed independently, following a predefined checklist of criteria of methodological quality.Results 22 trials met the inclusion criteria. Follow-up ranged from six weeks to three years. 12 of 14 studies measuring the cognitive outcome by means of the 70 point Alzheimer's disease assessment scale-cognitive subscale showed differences ranging from 1.5 points to 3.9 points in favour of the respective cholinesterase inhibitors. Benefits were also reported from all 12 trials that used the clinician's interview based impression of change scale with input from caregivers. Methodological assessment of all studies found considerable flaws-for example, multiple testing without correction for multiplicity or exclusion of patients after randomisation.Conclusion Because of flawed methods and small clinical benefits, the scientific basis for recommendations of cholinesterase inhibitors for the treatment of Alzheimer's disease is questionable.