Donepezil for mild and moderate Alzheimer's disease.
BACKGROUND
Alzheimer's disease is the most common cause of dementia in older people. One of the aims of therapy is to inhibit the breakdown of a chemical neurotransmitter, acetylcholine, by blocking the relevant enzyme. This can be done by a group of chemicals known as cholinesterase inhibitors. However, some (like tacrine) are associated with adverse effects such as hepatotoxicity, but E2020 (donepezil, Aricept) is thought to be more specific in its action, and safer.


OBJECTIVE
The objective of this review is to assess whether or not donepezil improves the well-being of patients with mild or moderate Alzheimer's disease.


METHODS
The Cochrane Dementia and Cognitive Improvement Group specialized register was searched using the terms 'donepezil', 'E2020' and 'Aricept'. Members of the Donepezil Study Group and Eisai Inc were contacted.


METHODS
All unconfounded, double-blind, randomized controlled trials in which treatment with donepezil was compared with placebo for patients with Alzheimer's disease.


METHODS
Data were extracted by one reviewer (JSB ), pooled where appropriate and possible, and the weighted mean differences or Peto odds ratios (95%CI) estimated. Where possible, intention-to-treat (ITT) data were used.


RESULTS
Eight trials are included, involving 2664 participants. The trials were of 12, 24 or 52 weeks duration in selected patients. Available outcome data cover domains including cognitive function and global clinical state, but data on several important dimensions of outcome are not available. For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared to placebo (1.9 points on the ADAS-Cog scale, WMD 1.86, 95%CI -2.60 to -1.11; 2.9 points on the ADAS-Cog scale, WMD -2.91, 95% CI -3.65 to -2.16)and for 10mg/day donepezil compared to placebo at 52 weeks (1.7 MMSE points, 95% CI, -2.59 to -0.82). The results of three studies show some improvement in global clinical state (assessed by an independent clinician) in those treated with 5 and 10mg/day of donepezil compared with placebo at 12 and 24 weeks. The patients' own ratings of their Quality of Life showed no benefit of donepezil compared with placebo. There were significantly more withdrawals before the end of treatment from the 10mg/day (but not the 5mg/day) donepezil group compared with placebo which may have resulted in some overestimation of beneficial changes at 10mg/day A variety of adverse effects were recorded, with more incidents of nausea, vomiting, diarrhoea and anorexia in the 10mg/day group compared with placebo and the 5mg/day group, but very few patients left a trial as a direct result of the intervention.


CONCLUSIONS
In selected patients with mild or moderate Alzheimer's disease treated for periods of 12, 24 or 52 weeks, donepezil produced modest improvements in cognitive function and study clinicians rated global clinical state more positively in treated patients. No improvements were present on patient self-assessed quality of life and data on many important outcomes are not available. The practical importance of these changes to patients and carers is unclear.
Birks
J S
JS
Department of Clinical Geratology, University of Oxford, Oxford, UK, OX2 6HE. jacqueline.birks@geratology.ox.ac.uk
Melzer
D
D
Beppu
H
H
D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines