Raina Parminder, Santaguida Pasqualina, Ismaila Afisi, Patterson Christopher, Cowan David, Levine Mitchell, Booker Lynda, Oremus Mark
McMaster University, Hamilton, Ontario, Canada.
Ann Intern Med. 2008 Mar 4;148(5):379-97. doi: 10.7326/0003-4819-148-5-200803040-00009.
The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear.
To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia.
Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006.
English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale.
Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate.
96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior.
Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments.
Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.
美国食品药品监督管理局批准的5种治疗痴呆症的药物疗法在实现具有临床意义的改善方面的有效性尚不清楚。
综述胆碱酯酶抑制剂（多奈哌齐、加兰他敏、卡巴拉汀和他克林）以及神经肽修饰剂美金刚在实现具有临床意义的改善方面的证据，主要涉及痴呆症患者的认知、整体功能、行为和生活质量。
1986年1月至2006年11月的考克兰对照试验中央注册库、医学索引数据库、医学预印本数据库、荷兰医学文摘数据库、补充与替代医学数据库、护理学与健康领域数据库、老年学数据库和心理学文摘数据库。
如果英文随机对照试验评估了用于诊断为痴呆症的成年人的药物，未采用交叉设计，且在雅达量表上的质量评分至少为3，则纳入该综述。
提取有关研究特征和结果的数据，包括不良事件。计算效应量，并在适当情况下合并数据。
96篇代表59项独特研究的出版物符合本综述的条件。胆碱酯酶抑制剂和美金刚在认知和整体评估领域均有一致的效果，但汇总估计显示效应量较小。行为和生活质量领域的结果评估较少，且效果不太一致。大多数研究持续时间较短（6个月），这限制了它们检测痴呆症发病或进展延迟的能力。三项研究直接比较了不同的胆碱酯酶抑制剂，发现认知和行为方面没有差异。
现有研究的局限性包括持续时间短、仅纳入轻度至中度阿尔茨海默病患者、不良事件报告不佳、缺乏统计学显著性的明确定义、行为和生活质量结果评估有限以及不同治疗方法的直接比较有限。
用胆碱酯酶抑制剂和美金刚治疗痴呆症可在痴呆症认知和整体评估指标上产生具有统计学意义但临床上边际性的改善。
