Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease

In patients with moderate or severe Alzheimer's disease receiving donepezil, those assigned to continue donepezil had less cognitive decline than did those assigned to discontinue donepezil. The combination of donepezil and memantine did not confer benefits over donepezil alone. Most studies evaluating cholinesterase inhibitors for the treatment of Alzheimer's disease have focused on patients with mild-to-moderate disease. Despite questions about the methods used in the trials 1 and about the clinical significance of reported benefits, 1 , 2 guidelines advocate treatment with a cholinesterase inhibitor, although some recommend discontinuation when Alzheimer's disease becomes severe. 3 Evidence of the efficacy of memantine has been shown primarily in patients with moderate or severe Alzheimer's disease. 4 The findings of a study showing that combination therapy with memantine and a cholinesterase inhibitor was more effective than treatment with a cholinesterase inhibitor alone 5 have not been replicated. 6 Results . . .