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.
After several years of treatment with donepezil, patients with moderate-to-severe Alzheimer disease appeared to derive cognitive benefit from continuing this drug; substituting or adding memantine was not fruitful. However, neither drug significantly affected outcomes that are important from the caregiver’s perspective. Drug therapies for AD clearly have some measurable benefits, but their overall impact on most patients and families remains limited.
- Howard R et al. Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med 2012 Mar 8; 366:893.