A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
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DOI：
10.1212/wnl.50.1.136
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发表时间：
1998-01-01
期刊：
影响因子：
9.9
通讯作者：
Walshe, TM
中科院分区：
文献类型：
--
作者：
Rogers, SL;Farlow, MR;Walshe, TM
一项多中心、双盲研究调查了多奈哌齐治疗轻度至中度阿尔茨海默病 (AD) 患者的有效性和安全性。患者被随机分配接受安慰剂 (n = 162)、5 mg/d 多奈哌齐 (n = 154) 或 10 mg/d 多奈哌齐 (n = 157) 治疗，疗程为 24 周，随后进行为期 6 周的单盲安慰剂清除。主要疗效指标是阿尔茨海默病评估量表 (ADAS-cog) 的认知部分和基于临床医生访谈的变化评估 (CIBIC plus)，同时使用简易精神状态检查 (MMSE)、临床痴呆评定量表 - 方框总和 (CDR-SB) 和患者评定的生活质量 (QoL) 作为次要指标。通过 ADAS-cog 测量，在第 12、18 和 24 周时，与安慰剂组相比，5 毫克/天和 10 毫克/天多奈哌齐组的认知功能显着改善。与安慰剂相比，5 毫克/天和 10 毫克/天多奈哌齐组的临床医生对 CIBIC plus 的总体评分也有所改善。在 6 周安慰剂清除阶段结束时，三组的 ADAS-cog 评分和 CIBIC plus 评分没有显着差异。 5 mg/d 组和 10 mg/d 组在 MMSE 和 CDR-SB 方面也一致观察到显着的治疗益处，但对患者评定的 QoL 没有一致的影响。 10 mg/d 组比 5 mg/d 组或安慰剂组更常报告胆碱能副作用（主要是腹泻、恶心和呕吐）。副作用是短暂的，严重程度一般较轻。这些数据表明多奈哌齐是一种耐受性良好的药物，可改善轻度至中度 AD 患者的认知和整体功能。
The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.