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


Courtney, C., Farrell, D., Gray, R., Hills, R., Lynch, L., Sellwood, E., Edwards, S., Hardyman, W., Raftery, J., Crome, P., Lendon, C., Shaw, H. and Bentham, P. AD2000 Collaborative Group (2004) Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. The Lancet, 363, (9427), 2105-2115. (doi:10.1016/S0140-6736(04)16499-4).

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Description/Abstract

Summary
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.

Item Type: Article
ISSNs: 0140-6736 (print)
Related URLs:
Subjects: R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QD Chemistry
Divisions: University Structure - Pre August 2011 > School of Medicine > Community Clinical Sciences
ePrint ID: 24313
Date Deposited: 29 Mar 2006
Last Modified: 27 Mar 2014 18:13
URI: http://eprints.soton.ac.uk/id/eprint/24313

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