Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer's disease: a subgroup analysis in patients already taking or not taking concomitant memantine.

BACKGROUND/AIMS: A large multicenter trial of donepezil 23 mg/day versus donepezil 10 mg/day for moderate-to-severe Alzheimer's disease allowed patients taking concomitant memantine. We evaluated the efficacy/safety of donepezil 23 and 10 mg/day in this trial, with respect to concomitant memantine use.

METHODS

Prespecified analysis of data from a 24-week, randomized, double-blind trial. Patients were randomized to donepezil doses (23 vs. 10 mg/day) and stratified by concomitant memantine use (yes or no). Efficacy and safety were assessed for each donepezil dose in subgroups taking or not taking concomitant memantine.

RESULTS

At week 24, donepezil 23 mg/day provided significant cognitive benefits over 10 mg/day (p < 0.01) on the Severe Impairment Battery, with or without concomitant memantine (ANCOVA adjusted for baseline score, country and treatment). The higher dose showed no benefit on the global function, Mini-Mental State Examination or activities of daily living measures in either memantine subgroup. Rates of treatment-emergent adverse events (AEs) were higher for donepezil 23 mg/day with memantine (80.7%) than 23 mg/day without memantine (69.7%) or 10 mg/day with/without memantine (66.7/62.0%); across all treatment groups, most events were mild/moderate in severity. Individual rates of serious AEs were low (<1.0%), regardless of concomitant memantine use.

CONCLUSION

In this population, concomitant memantine use did not alter the response profile of donepezil 23 vs. 10 mg/day. Donepezil 23 mg was generally safe and well tolerated among patients receiving donepezil alone and among patients receiving a combination of donepezil and memantine therapy.