The donepezil study reported by Greenberg et al1 confirms the short-term beneficial symptomatic effect of the drug on cognitive parameters in Alzheimer disease (AD). However, whereas 12 weeks is considered to be the standard duration of therapy to assess clinical improvement in a chronic disease such as AD, it remains totally unclear to us why the authors decided on a 6-week active trial period. Presumably, favorable results at 6 weeks in previous clinical trials might have been the influencing factor.2,4 This distinction between statistically significant improvements on the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) and lack of clinical relevance (there's no improvement on the "caregiver-rated global impression of change") cannot go unnoticed. The patients were suffering from mild dementia. Despite mild improvement on the ADAS-cog at 6 weeks, the study failed to show any improvement on the functional scale, this at the time when the drug appears to have its maximal beneficial effect. This simply means that there was no absolute clinically meaningful improvement in the donepezil group at all. Unless studies can demonstrate improvement in quality of life and a delay in the drug's progressive effect on severe dependency or institutionalization, the role of donepezil, and perhaps of cholinesterase inhibitors in general, remains increasingly questionable, and hence does not justify its widespread use in the treatment of AD.
Deleu D, Hanssens Y. Donepezil in the Treatment of Alzheimer Disease. Arch Neurol. 2000;57(9):1380-1383. doi: