%0 Journal Article %J J Alzheimers Dis %D 2016 %T Efficacy and Safety of Sustained Release Donepezil High Dose versus Immediate Release Donepezil Standard Dose in Japanese Patients with Severe Alzheimer's Disease: A Randomized, Double-Blind Trial. %A Homma, Akira %A Atarashi, Hirotsugu %A Kubota, Naoki %A Nakai, Kenya %A Takase, Takao %K Aged %K Alzheimer Disease %K Cholinesterase Inhibitors %K Delayed-Action Preparations %K Double-Blind Method %K Female %K Humans %K Indans %K Japan %K Male %K Mental Status Schedule %K Nootropic Agents %K Outpatients %K Piperidines %K Psychiatric Status Rating Scales %K Severity of Illness Index %K Treatment Outcome %X

BACKGROUND: Donepezil is an established treatment for mild, moderate, and severe Alzheimer's disease (AD). An international study demonstrated superior efficacy of sustained release (SR) 23 mg/day donepezil over immediate release (IR) 10 mg/day donepezil for cognitive function, but not global function in moderate-to-severe AD.

OBJECTIVE: To demonstrate the superiority of SR 23 mg/day donepezil over IR 10 mg/day donepezil in Japanese patients with severe AD (SAD).

METHODS: In this multicenter, randomized, double-blind, parallel-group study, Japanese outpatients with SAD were randomly assigned to continue IR 10 mg/day or switch to SR 23 mg/day for 24 weeks. Endpoints included the Severe Impairment Battery (SIB), Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus), and safety.

RESULTS: Overall, 166 and 185 patients were randomized to receive IR 10 mg/day and SR 23 mg/day, respectively. SR 23 mg/day was not statistically superior to IR 10 mg/day by SIB (least squares mean difference [LSMD]: 0.0; 95% confidence interval [CI]: -1.7, 1.8; p = 0.981) or CIBIC-plus (LSMD: 0.2; 95% CI: 0.0, 0.4; p = 0.080). Common adverse events in the SR 23 mg group were decreased appetite, vomiting, diarrhea, and contusion. Safety findings were consistent with known safety profiles of donepezil.

CONCLUSION: SR 23 mg/day donepezil was not superior to IR 10 mg/day donepezil regarding the efficacy endpoints for Japanese SAD. Considering that a 10 mg/day dose is approved for SAD in Japan, the present findings suggest that IR 10 mg/day donepezil is the optimal dosage for Japanese patients with SAD.

%B J Alzheimers Dis %V 52 %P 345-57 %8 2016 03 11 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26967222?dopt=Abstract %R 10.3233/JAD-151149