Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study.
BACKGROUND
The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimer's disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living.


METHODS
We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimer's disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for patients with data at baseline and at one or more other timepoints (modified intent-to-treat population) with last observation carried forward used to replace missing data.


RESULTS
95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in SIB scores and declined less in ADCS-ADL-severe scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n=20) than in the placebo group (n=8).


CONCLUSIONS
Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes.
Karolinska Institutet, Alzheimer's Disease Research Center, Department of Neurotec, Division of Geriatric Medicine, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden. Electronic address: bengt.winblad@ki.se.
Bengt
B
Winblad
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.
Lena
L
Kilander
Section of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden.
Sture
S
Eriksson
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University, Malmö, Sweden.
Lennart
L
Minthon
Department of Primary Care, Kalix Vårdcentral, Kalix, Sweden.
Stellan
S
Båtsman
Pfizer AB, PO Box 501, Täby, Sweden.
Anna-Lena
AL
Wetterholm
Pfizer AB, PO Box 501, Täby, Sweden.
Catarina
C
Jansson-Blixt
Pfizer AB, PO Box 501, Täby, Sweden.
Anders
A
Haglund
D000203:Activities of Daily Living; D000544:Alzheimer Disease / Q000145:classification / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D000077265:Donepezil; D004311:Double-Blind Method; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009735:Nursing Homes; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil