Long-term safety and efficacy of donepezil in patients with severe Alzheimer's disease: results from a 52-week, open-label, multicenter, extension study in Japan.
OBJECTIVE
A 6-month, randomized, double-blind, placebo-controlled study was extended to evaluate long-term safety and efficacy of donepezil in community-dwelling Japanese patients with severe Alzheimer's disease (AD).


METHODS
189 patients were enrolled from the double-blind study into a 52-week, open-label extension study. After a 2- to 8-week washout, donepezil was escalated within 6 weeks to 10 mg/day. Main outcomes were Severe Impairment Battery (SIB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale for severe AD (ADCS-ADL-sev) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Safety parameters were monitored throughout.


RESULTS
Overall, mean change from extension study baseline in SIB scores improved until week 24; however, scores were influenced by prior treatment during the double-blind study and by length of washout. Patients treated with donepezil retained some treatment benefits after a washout of 2-4 weeks but lost all treatment benefits after a washout of 4-8 weeks. There was no change in ADCS-ADL-sev or BEHAVE-AD scores. Adverse events were consistent with the known donepezil safety profile.


CONCLUSIONS
Donepezil is effective and safe for symptomatic treatment of severe AD for at least 1 year. Patients who receive donepezil 10 mg daily with little or no interruption achieve the best long-term outcome.
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
Takase
Takao
T
Ohbayashi
Toshio
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil