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Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study

Winblad, B ; Kilander, L ; Eriksson, S ; Minthon, Lennart LU ; Batsman, S ; Wetterholm, AL ; Jarisson-Blixt, C and Hoglund, A (2006) In The Lancet 367(9516). p.1057-1065
Abstract
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... (More)
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. Findings 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% Cl 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). Interpretation Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet
volume
367
issue
9516
pages
1057 - 1065
publisher
Elsevier
external identifiers
  • pmid:16581404
  • wos:000236673200029
  • scopus:33645741379
ISSN
1474-547X
DOI
10.1016/S0140-6736(06)68350-5
language
English
LU publication?
yes
id
e8b92560-cbce-40c4-9b5b-b5e709bc7c3d (old id 414367)
date added to LUP
2016-04-01 12:27:51
date last changed
2020-12-16 01:12:41
@article{e8b92560-cbce-40c4-9b5b-b5e709bc7c3d,
  abstract     = {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. Findings 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% Cl 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). Interpretation Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes.},
  author       = {Winblad, B and Kilander, L and Eriksson, S and Minthon, Lennart and Batsman, S and Wetterholm, AL and Jarisson-Blixt, C and Hoglund, A},
  issn         = {1474-547X},
  language     = {eng},
  number       = {9516},
  pages        = {1057--1065},
  publisher    = {Elsevier},
  series       = {The Lancet},
  title        = {Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study},
  url          = {http://dx.doi.org/10.1016/S0140-6736(06)68350-5},
  doi          = {10.1016/S0140-6736(06)68350-5},
  volume       = {367},
  year         = {2006},
}