胆碱酯酶抑制剂对阿尔茨海默氏症。
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比尔克J
胆碱酯酶抑制剂对阿尔茨海默氏症。
Cochrane数据库系统启2006年1月25日,(1):CD005593。
- PubMed ID
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16437532 (在PubMed]
- 文摘
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背景:介绍以来第一个胆碱酯酶抑制剂(ChEI)在1997年,大多数临床医生,可能大多数患者会考虑胆碱能药物,多奈哌齐,加兰他敏和卡巴拉汀,第一线药物治疗轻度至中度阿尔茨海默氏症。药物的药理性质稍有不同,但他们都通过抑制乙酰胆碱的分解工作,一个重要的与记忆相关的神经递质,通过阻断乙酰胆碱酯酶的酶。这些药物能达到的最修改阿尔茨海默氏症的表现。科克伦评论每个ChEI阿尔茨海默病已经完成(比尔克2005年,比尔克2005 b和阿来2005)。尽管证据从临床研究和干预临床经验ChEIs是否有效的争论仍在继续。目的:评估多奈哌齐的影响,加兰他敏和卡巴拉汀在患有轻度,中度或重度阿尔茨海默病痴呆。搜索策略:Cochrane痴呆和认知改善组织的专业注册使用术语“多奈哌齐”,搜索“E2020”、“过程”,galanthamin * galantamin * reminyl,卡巴拉汀,艾斯,“ENA 713”和ENA - 713 2005年6月12日。这个寄存器包含最新的记录所有主要卫生保健数据库和许多正在进行的临床试验数据库。选择标准:所有unconfounded、盲随机试验中ChEI与安慰剂治疗患者或其他ChEI轻微、中度或重度痴呆阿尔茨海默氏症。数据收集和分析:数据提取,一位评论家(JSB),汇集在适当的地方,可能和联合治疗效果,或治疗的风险和益处。主要结果:结果13个随机,双盲,安慰剂对照试验表明,治疗6个月和一年的时期,与多奈哌齐、加兰他敏或卡巴拉汀推荐剂量的轻度,中度或重度痴呆由于阿尔茨海默病产生了认知功能的改善,平均-2.7分(95% ci -3.0 - -2.3),在70点的中档ADAS-Cog规模。 Study clinicians blind to other measures rated global clinical state more positively in treated patients. Benefits of treatment were also seen on measures of activities of daily living and behaviour. None of these treatment effects are large. There is nothing to suggest the effects are less for patients with severe dementia or mild dementia, although there is very little evidence for other than mild to moderate dementia.More patients leave ChEI treatment groups, approximately 29 %, on account of adverse events than leave the placebo groups (18%). There is evidence of more adverse events in total in the patients treated with a ChEI than with placebo. Although many types of adverse event were reported, nausea, vomiting, diarrhoea, were significantly more frequent in the ChEI groups than in placebo. There are four studies, all supported by one of the pharmaceutical companies, in which two ChEIs were compared, two studies of donepezil compared with galantamine, and two of donepezil compared with rivastigmine. In three studies the patients were not blinded to treatment, only the fourth, DON vs RIV/Bullock is double blind. Two of the studies provide little evidence, they are of 12 weeks duration, which is barely long enough to complete the drug titration. There is no evidence from DON vs GAL/Wilcock of a treatment difference between donepezil and galantamine at 52 weeks for cognition, activities of daily living, the numbers who leave the trial before the end of treatment, the number who suffer any adverse event, or any specific adverse event. There is no evidence from DON vs RIV/Bullock of a difference between donepezil and rivastigmine for cognitive function, activities of daily living and behavioural disturbance at two years. Fewer patients suffer adverse events on donepezil than rivastigmine. AUTHORS' CONCLUSIONS: The three cholinesterase inhibitors are efficacious for mild to moderate Alzheimer's disease. It is not possible to identify those who will respond to treatment prior to treatment. There is no evidence that treatment with a ChEI is not cost effective. Despite the slight variations in the mode of action of the three cholinesterase inhibitors there is no evidence of any differences between them with respect to efficacy. There appears to be less adverse effects associated with donepezil compared with rivastigmine. It may be that galantamine and rivastigmine match donepezil in tolerability if a careful and gradual titration routine over more than three months is used. Titration with donepezil is more straightforward and the lower dose may be worth consideration.