Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): Randomised double-blind trial

AD2000 Collaborative Group and Pritchard, Antonia (2004) Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): Randomised double-blind trial. Lancet, 363 9427: 2105-2115. doi:10.1016/S0140-6736(04)16499-4


Author AD2000 Collaborative Group
Pritchard, Antonia
Title Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): Randomised double-blind trial
Journal name Lancet   Check publisher's open access policy
ISSN 0140-6736
1474-547X
Publication date 2004-06-26
Sub-type Article (original research)
DOI 10.1016/S0140-6736(04)16499-4
Volume 363
Issue 9427
Start page 2105
End page 2115
Total pages 11
Place of publication London, U.K.
Publisher Lancet Publishing Group
Language eng
Subject 11 Medical and Health Sciences
1103 Clinical Sciences
Formatted abstract
Background
Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long?

Methods
565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models.

Findings
Cognition averaged 0·8 MMSE (mini-mental state examination) points better (95% Cl 0·5–1·2; p<0·0001) and functionality 1·0 BADLS points better (0·5–1·6; p<0·0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42% vs 44% at 3 years; p=0·4) or progression of disability (58% vs 59% at 3 years; p=0·4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0·97 (95% Cl 0·72–1·30; p=0·8); the relative risk of progression of disability or entering institutional care was 0·96 (95% Cl 0·74–1·24; p=0·7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil.

Interpretation
Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than Cholinesterase inhibitors are needed for Alzheimer's disease.
Keyword Central nervous system disease
Degenerative disease
Cerebral disorder
Nervous system diseases
Piperidine derivatives
Enzyme inhibitor
Anticholinesterase agent
Enzyme
Hydrolases
Esterases
Carboxylic ester hydrolases
Acetylcholinesterase
Nootropic agent
Psychotropic
Treatment efficiency
Antialzheimer agent
Chemotherapy
Double blind study
Clinical trial
Donepezil
Long term
Alzheimer disease
Q-Index Code C1
Additional Notes Contributors to Genetic research—Molecular Psychiatry, University of Birmingham, Birmingham, UK (J Coates, N Craddock, J Harris, C Lendon, A Pritchard).

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Mon, 18 Jan 2010, 10:13:04 EST by Jon Swabey on behalf of Faculty Of Health Sciences