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

• Published in: Dementia and geriatric cognitive disorders 2012-01, Vol.33 (2-3), p.164-173
• Main Authors: Doody, Rachelle S., Geldmacher, David S., Farlow, Martin R., Sun, Yijun, Moline, Margaret, Mackell, Joan
• Format: Article
• Language: English
• Subjects: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease - diagnosis; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Geriatric Assessment - methods; Humans; Indans - administration & dosage; Indans - adverse effects; Intelligence Tests; Male; Medical sciences; Memantine - administration & dosage; Memantine - adverse effects; Neurology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Original Research Article; Pharmacology. Drug treatments; Piperidines - administration & dosage; Piperidines - adverse effects; Psychiatric Status Rating Scales; Serotoninergic system; Treatment Outcome
• ISSN: 1420-8008; 1421-9824
• DOI: 10.1159/000338236

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 (