Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E
Division of Neurology, UBC Hospital, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, BC, Canada.
Neurology. 2001 Aug 28;57(4):613-20. doi: 10.1212/wnl.57.4.613.
To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score < or =6 at baseline).
Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+).
Patients' mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE scores at baseline were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary measures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated patients completed the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of placebo-treated patients, the majority of which were rated mild in severity; 8% of donepezil- and 6% of placebo-treated patients discontinued because of AE. Laboratory and vital sign abnormalities were similar between the treatment groups.
These data suggest that donepezil's benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.
探讨多奈哌齐治疗中度至重度阿尔茨海默病（AD）患者（标准化简易精神状态检查表[sMMSE]评分为5至17分；基线时功能评估分期评分≤6分）的疗效和安全性。
在这项为期24周的双盲、安慰剂对照试验中，290例患者被随机分配接受治疗。根据临床医生的判断，患者在前28天接受5mg/天的多奈哌齐治疗，此后接受10mg/天的治疗（n = 144）或安慰剂治疗（n = 146）。主要结局指标是基于临床医生访谈并结合照料者意见的变化印象量表（CIBIC+）。
患者的平均年龄为73.6岁（范围48至92岁）。治疗组之间的基线人口统计学特征相似。多奈哌齐组基线时最小二乘（LS）均值±标准误的sMMSE评分为11.7±0.35，安慰剂组为12.0±0.34。与安慰剂相比，接受多奈哌齐治疗的患者在直至第24周的所有访视时CIBIC+评分均显示出益处（p < 0.001），在第24周末次观察值结转（LOCF）时也显示出益处（p < 0.0001）。所有其他次要指标（包括sMMSE、严重损害量表、痴呆症残疾评估、功能评定量表和神经精神科问卷）在第24周LOCF时显示两组之间存在显著差异，支持多奈哌齐治疗。84%接受多奈哌齐治疗和86%接受安慰剂治疗的患者完成了试验。83%接受多奈哌齐治疗和80%接受安慰剂治疗的患者经历了不良事件（AE），其中大多数严重程度为轻度；8%接受多奈哌齐治疗和6%接受安慰剂治疗的患者因AE而停药。治疗组之间的实验室检查和生命体征异常情况相似。
这些数据表明，多奈哌齐的益处扩展至比先前研究阶段更晚期的AD阶段，且耐受性良好。
