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.
abstract: 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.
  
  
  
  To demonstrate the superiority of SR 23 mg/day donepezil over IR 10 mg/day donepezil in Japanese patients with severe AD (SAD).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Tokyo Dementia Care Research and Training Center, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Homma
authors.affiliation: Nippon Medical School Tama-Nagayama Hospital, Nippon Medical School, Tokyo, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Atarashi
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kubota
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Nakai
authors.affiliation: Eisai Co., Ltd., Tokyo, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Takase
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D003692:Delayed-Action Preparations; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007564:Japan; D008297:Male; D008609:Mental Status Schedule; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D010045:Outpatients; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D003692:Delayed-Action Preparations; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil
keywords: Alzheimer’s disease; Japan; cholinesterase inhibitors; donepezil; double-blind study