Doody R S, Geldmacher D S, Gordon B, Perdomo C A, Pratt R D
Department of Neurology, Baylor College of Medicine, 6550 Fannin Street, Suite 1801, Houston, TX 77030-3498, USA.
Arch Neurol. 2001 Mar;58(3):427-33. doi: 10.1001/archneur.58.3.427.
Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function.
To investigate the long-term benefits of donepezil treatment in patients with AD.
Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout).
All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged.
Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes.
After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events.
Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.
盐酸多奈哌齐是一种选择性乙酰胆碱酯酶抑制剂，已被批准用于轻度至中度重度阿尔茨海默病（AD）的症状性治疗。长达24周的对照临床试验表明，多奈哌齐治疗（5毫克/天和10毫克/天）能显著改善认知和整体功能。
研究多奈哌齐治疗对AD患者的长期益处。
对两项美国3期双盲、安慰剂对照临床试验进行多中心、开放标签、为期144周的扩展研究：一项为期15周的研究（12周治疗，随后3周安慰剂洗脱期）和一项为期30周的研究（24周治疗，随后6周安慰剂洗脱期）。
所有患者（N = 763）最初接受5毫克/天的多奈哌齐治疗6周，之后鼓励增加至10毫克/天。
主要疗效指标为阿尔茨海默病评估量表认知子量表和临床痴呆评定量表总分。
在较短的3周安慰剂洗脱期后，多奈哌齐相关益处又在开放标签治疗的额外24周内保持高于原始基线值。在108周的开放标签治疗中，与双盲研究中接受10毫克/天治疗的患者相比，阿尔茨海默病评估量表认知子量表得分的益处明显。相比之下，在6周安慰剂洗脱期后，多奈哌齐相关益处消失，所有患者组的得分降至原始基线值以下。尽管在重新开始用药后得分相对于新的开放标签研究基线得分有所改善，但患者仍低于原始基线值。最常见的不良事件与神经和消化系统有关，通常为轻度且短暂；17%的患者停药与不良事件有关。
多奈哌齐是一种有效且安全的药物，可用于轻度至中度重度AD长达144周（2.8年）的长期症状性治疗，持续治疗可能具有一些优势。
