Donepezil for the symptomatic treatment of patients with mild to moderate Alzheimer's disease: a meta‐analysis of individual patient data from randomised controlled trials

Abstract

Background The objective was to evaluate the efficacy and tolerability of donepezil (5 and 10 mg/day) compared with placebo in alleviating manifestations of mild to moderate Alzheimer's disease (AD). Method A systematic review of individual patient data from Phase II and III double‐blind, randomised, placebo‐controlled studies of up to 24 weeks and completed by 20 December 1999. The main outcome measures were the ADAS‐cog, the CIBIC‐plus, and reports of adverse events. Results A total of 2376 patients from ten trials were randomised to either donepezil 5 mg/day (n = 821), 10 mg/day (n = 662) or placebo (n = 893). Cognitive performance was better in patients receiving donepezil than in patients receiving placebo. At 12 weeks the differences in ADAS‐cog scores were 5 mg/day–placebo: − 2.1 [95% confidence interval (CI), − 2.6 to − 1.6; p < 0.001], 10 mg/day–placebo: − 2.5 ( − 3.1 to − 2.0; p < 0.001). The corresponding results at 24 weeks were − 2.0 ( − 2.7 to − 1.3; p < 0.001) and − 3.1 ( − 3.9 to − 2.4; p < 0.001). The difference between the 5 and 10 mg/day doses was significant at 24 weeks (p = 0.005). The odds ratios (OR) of improvement on the CIBIC‐plus at 12 weeks were: 5 mg/day–placebo 1.8 (1.5 to 2.1; p < 0.001), 10 mg/day–placebo 1.9 (1.5 to 2.4; p < 0.001). The corresponding values at 24 weeks were 1.9 (1.5 to 2.4; p = 0.001) and 2.1 (1.6 to 2.8; p < 0.001). Donepezil was well tolerated; adverse events were cholinergic in nature and generally of mild severity and brief in duration. Conclusion Donepezil (5 and 10 mg/day) provides meaningful benefits in alleviating deficits in cognitive and clinician‐rated global function in AD patients relative to placebo. Increased improvements in cognition were indicated for the higher dose. Copyright © 2004 John Wiley & Sons, Ltd.