Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan.
BACKGROUND
Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.


METHODS
We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini-mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.


RESULTS
The Revised Hasegawa Dementia Scale and mini-mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.


CONCLUSIONS
The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.
Nozawa
Motohiro
M
Department of Psychiatry, Juntendo Tokyo Koto Geriatric Medial Center, Juntendo University School of Medicine, Tokyo, Japan. nozawa060205@yahoo.co.jp
Ichimiya
Yosuke
Y
Nozawa
Eiko
E
Utumi
Yushi
Y
Sugiyama
Hideki
H
Murayama
Norio
N
Iseki
Eizo
E
Arai
Heii
H
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D018450:Disease Progression; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007564:Japan; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology
D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil