Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial.
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...
| Published in: | Lancet Vol. 363; no. 9427; pp. 2105 - 2116 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | clinical trial research tables/charts Journal Article |
| Published: |
Lancet
6/26/2004
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=106576773&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 106576773 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01406736 LAN jtl: Lancet issn: 01406736 maglogo: N pubinfo: dt: 6/26/2004 vid: 363 iid: 9427 pid: 1297 pub: Lancet place: Philadelphia, Pennsylvania artinfo: ui: 106576773 106576773 NLM15220031 2005032409 10.1016/s0140-6736(04)16499-4 NLM15220031 106576773 ppf: 2105 ppct: 11 formats: fmt: @attributes: type: P tig: atl: Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial. aug: au: Courtney, C Farrell, D Gray, R Hills, R Lynch, L Sellwood, E Edwards, S Hardyman, W Raftery, J Crome, P Lendon, C Shaw, H Bentham, P affil: Trials Unit, University of Birmingham, Birmingham, UK sug: subj: Alzheimer's Disease Drug Therapy Donepezil Therapeutic Use Activities of Daily Living Aged Aged, 80 and Over Alzheimer's Disease Diagnosis Cognition Confidence Intervals Cost Benefit Analysis Descriptive Statistics Disease Progression Donepezil Administration and Dosage Donepezil Economics Double-Blind Studies Middle Age Neuropsychological Tests Odds Ratio Placebos Therapeutic Use Prospective Studies Questionnaires Random Assignment Relative Risk Scales Funding Source Human Aged: 65+ years Aged, 80 & over Middle Aged: 45-64 years ab: 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% CI 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% CI 0.72-1.30; p=0.8); the relative risk of progression of disability or entering institutional care was 0.96 (95% CI 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. pubtype: Academic Journal doctype: clinical trial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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