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

Rachelle S. Doody, David S. Geldmacher, Martin Farlow, Yijun Sun, Margaret Moline, Joan MacKell

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalDementia and Geriatric Cognitive Disorders
Volume33
Issue number2-3
DOIs
StatePublished - Jun 2012

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Memantine
Alzheimer Disease
Safety
donepezil
Therapeutics
Activities of Daily Living
Multicenter Studies

Keywords

  • Alzheimer's disease
  • Clinical trials
  • Cognition
  • Donepezil
  • Memantine

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Cognitive Neuroscience

Cite this

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. / Doody, Rachelle S.; Geldmacher, David S.; Farlow, Martin; Sun, Yijun; Moline, Margaret; MacKell, Joan.

In: Dementia and Geriatric Cognitive Disorders, Vol. 33, No. 2-3, 06.2012, p. 164-173.

Research output: Contribution to journalArticle

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abstract = "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.",
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