Donepezil for dementia due to Alzheimer's disease.Cochrane Database Syst Rev 2006; (1):CD001190CD
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.
The objective of this review is to assess whether donepezil improves the well-being of patients with dementia due to Alzheimer's disease.
The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched using the terms 'donepezil', 'E2020' and 'Aricept' on 12 June 2005. This Register contains up-to-date records of all major health care databases and many ongoing trial databases. Members of the Donepezil Study Group and Eisai Inc were contacted.
All unconfounded, double-blind, randomized controlled trials in which treatment with donepezil was compared with placebo for patients with mild, moderate or severe dementia due to Alzheimer's disease.
DATA COLLECTION AND ANALYSIS
Data were extracted by one reviewer (JSB), pooled where appropriate and possible, and the pooled treatment effects, or the risks and benefits of treatment estimated.
23 trials are included, involving 5272 participants. Most trials were of 6 months or less duration in selected patients. Available outcome data cover domains including cognitive function, activities of daily living, behaviour , global clinical state and health care resource costs. For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared with placebo on the ADAS-Cog scale (-2.01 points MD, 95%CI -2.69 to -1.34, p<0.00001); -2.80 points, MD 95% CI -3.74 to -2.10, p<0.00001) and for 10 mg/day donepezil compared with placebo at 52 weeks (1.84 MMSE points, 95% CI, 0.53 to 3.15, p=0.006). The results show some improvement in global clinical state (assessed by a clinician) in people treated with 5 and 10 mg/day of donepezil compared with placebo at 24 weeks for the number of patients showing improvement or no change (OR 2.18, 95% CI 1.53 to 3.11, p=<0.0001, OR 2.38, 95% CI 1.78 to 3.19, p<0.00001). Benefits of treatment were also seen on measures of activities of daily living and behaviour, but not on the quality of life score . There were significantly more withdrawals before the end of treatment from the 10 mg/day (but not the 5 mg/day) donepezil group compared with placebo which may have resulted in some overestimation of beneficial changes at 10 mg/day. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. Two studies presented results for health resource use, and the associated costs. There were no significant differences between treatment and placebo for any item, the cost of any item, and for the total costs, and total costs including the informal carer costs. A variety of adverse effects were recorded, with more incidents of nausea, vomiting, diarrhoea, muscle cramps, dizziness, fatigue and anorexia (significant risk associated with treatment) in the 10 mg/day group compared with placebo but very few patients left a trial as a direct result of the intervention.