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

Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial
Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial
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.
0140-6736
2105-2115
Courtney, C.
4f698849-6860-4988-bcf9-8051d28f2143
Farrell, D.
4e309024-c894-455a-af63-387d734c4116
Gray, R.
ae56443f-4f05-4091-afb4-a50beb966dae
Hills, R.
7c8318be-4842-45dd-9141-6b6e75b2b1e9
Lynch, L.
efbaa51f-dfd0-4451-b011-b5ce7bc60e5c
Sellwood, E.
64a4830a-43ad-489c-8a5e-76db078dfa49
Edwards, S.
340b6435-5d2e-4eec-bb37-a67ccb66355d
Hardyman, W.
7cfa4786-bf1f-447b-b73c-5efdf13dbe9b
Raftery, J.
27c2661d-6c4f-448a-bf36-9a89ec72bd6b
Crome, P.
d5161f70-fc77-43db-be03-8f2d9ea27d58
Lendon, C.
2759aae7-b32c-4f2d-8346-316b0c61f5c2
Shaw, H.
b528ce74-848b-4aae-87da-4ef406826841
Bentham, P.
8e1de862-3bd5-44b1-8884-a07e3241b818
AD2000 Collaborative Group
Courtney, C.
4f698849-6860-4988-bcf9-8051d28f2143
Farrell, D.
4e309024-c894-455a-af63-387d734c4116
Gray, R.
ae56443f-4f05-4091-afb4-a50beb966dae
Hills, R.
7c8318be-4842-45dd-9141-6b6e75b2b1e9
Lynch, L.
efbaa51f-dfd0-4451-b011-b5ce7bc60e5c
Sellwood, E.
64a4830a-43ad-489c-8a5e-76db078dfa49
Edwards, S.
340b6435-5d2e-4eec-bb37-a67ccb66355d
Hardyman, W.
7cfa4786-bf1f-447b-b73c-5efdf13dbe9b
Raftery, J.
27c2661d-6c4f-448a-bf36-9a89ec72bd6b
Crome, P.
d5161f70-fc77-43db-be03-8f2d9ea27d58
Lendon, C.
2759aae7-b32c-4f2d-8346-316b0c61f5c2
Shaw, H.
b528ce74-848b-4aae-87da-4ef406826841
Bentham, P.
8e1de862-3bd5-44b1-8884-a07e3241b818

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).

Record type: Article

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.

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Published date: 2004
Organisations: Community Clinical Sciences

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Local EPrints ID: 24313
URI: https://eprints.soton.ac.uk/id/eprint/24313
ISSN: 0140-6736
PURE UUID: 11a2f875-937d-4bc7-8a30-429bf9939c69

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Date deposited: 29 Mar 2006
Last modified: 05 Oct 2018 12:04

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Contributors

Author: C. Courtney
Author: D. Farrell
Author: R. Gray
Author: R. Hills
Author: L. Lynch
Author: E. Sellwood
Author: S. Edwards
Author: W. Hardyman
Author: J. Raftery
Author: P. Crome
Author: C. Lendon
Author: H. Shaw
Author: P. Bentham

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