After several years of donepezil therapy, donepezil (but not memantine) conferred modest benefits.

A man with Alzheimer disease (AD) has been taking donepezil (Aricept or a generic), and his dementia is progressing. Do you continue or stop the drug? Do you substitute or add memantine (Namenda)? To answer these questions, U.K. researchers conducted a partially industry-supported, randomized, placebo-controlled trial involving 295 community-dwelling patients with moderate-to-severe AD (mean Mini-Mental State Exam [MMSE] score, 9 out of 30) who had received donepezil for several years. Patients were assigned to continue donepezil alone, stop donepezil and start memantine, take both drugs, or take neither drug.


During 1 year of follow-up, MMSE scores and activities-of-daily-living scores indicated deterioration in all four groups. Patients who continued donepezil alone had significantly less deterioration on these scores than patients who stopped donepezil; the MMSE difference of 2 points was considered clinically important by prespecified criteria. Memantine was also associated with statistically less deterioration than no memantine on both scores, but differences were small and not considered clinically important. Adding memantine to donepezil had no benefit over donepezil monotherapy. Neither drug significantly influenced important secondary outcomes: caregivers' assessment of patients' quality of life and caregivers' own psychological symptoms.

Citation(s):

Howard R et al. Donepezil and memantine for moderate-to-severe Alzheimer's disease. N Engl J Med 2012 Mar 8; 366:893.