Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Homma, A, Atarashi, H, Kubota, N, Nakai, K, Takase, T |
Journal | J Alzheimers Dis |
Volume | 52 |
Issue | 1 |
Pagination | 345-57 |
Date Published | 2016 03 11 |
ISSN | 1875-8908 |
Keywords | Aged, Alzheimer Disease, Cholinesterase Inhibitors, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Indans, Japan, Male, Mental Status Schedule, Nootropic Agents, Outpatients, Piperidines, Psychiatric Status Rating Scales, Severity of Illness Index, Treatment Outcome |
Abstract | 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. |
DOI | 10.3233/JAD-151149 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26967222 |