Donepezil treatment of patients with severe Alzheimer's disease in a Japanese population: results from a 24-week, double-blind, placebo-controlled, randomized trial.
OBJECTIVE
A 24-week, randomized, parallel-group, double-blind placebo-controlled study was conducted to evaluate the efficacy and tolerability of donepezil in severe Alzheimer's disease (AD).


METHODS
Patients with severe AD (Mini-Mental State Examination score 1-12; modified Hachinski Ischemic Score < or =6; Functional Assessment Staging > or =6) were enrolled in this study in Japan. A total of 325 patients were randomized to donepezil 5 mg/day (n = 110), donepezil 10 mg/day (n = 103) or placebo (n = 112). Primary outcome measures were change from baseline to endpoint in the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus) at the endpoint visit.


RESULTS
Donepezil 5 mg/day and 10 mg/day were significantly superior to placebo on the SIB, with a least-squares mean treatment difference of 6.7 and 9.0, respectively (p < 0.001 compared with placebo). CIBIC-plus analyses showed significant differences in favor of donepezil 10 mg/day over placebo at endpoint (p = 0.003). A statistically significant dose-response relationship was demonstrated with the SIB and CIBIC-plus. Donepezil was well tolerated.


CONCLUSIONS
This study confirmed the effectiveness of donepezil 10 mg/day in patients with severe AD and demonstrated a significant dose-response relationship. Donepezil at dosages of both 5 mg/day and 10 mg/day is safe and well tolerated in Japanese patients with severe AD.
Homma
Akira
A
Dementia Interventional Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan. ahomma@tmig.or.jp
Imai
Yukimichi
Y
Tago
Hisao
H
Asada
Takashi
T
Shigeta
Masahiro
M
Iwamoto
Toshihiko
T
Takita
Masashi
M
Arimoto
Itaru
I
Koma
Hiroshi
H
Ohbayashi
Toshio
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage*; D007564:Japan; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000008:administration & dosage*; D010880:Piperidines / Q000008:administration & dosage*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil