Efficacy

• the AD2000 trial examined long-term donepezil treatment in patients with Alzheimer's disease (1)
  • 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate
  • primary endpoints used in the study were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS)
  • groups did not differ for progression of disability at 1 year (13% v 19%, p=0.3) or 3 years (55% v 53%, p=0.9). There was no significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; P=0·4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0·97 (95% CI 0·72–1·30; P=0·8); the relative risk of progression of disability was 1.02 (CI 0.72 to 1.45)
  • therefore, based on this study evidence, long term treatment with donepezil did not delay entry to institutional care or progression of disability
• a commentary however suggested that this study may not have had adequate power to detect differences in several outcomes. Also it was noted that the broad confidence intervals suggest that donepezil could be associated with a 30-45% increase or a 28% decrease in primary outcomes (2)

Reference

1. AD2000 Collaborative Group. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. Lancet 2004;363:2105-15.
2. Commentary. Evidence Based Medicine 2005;10(1):15.