Donepezil for dementia due to Alzheimer's disease

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Abstract
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 donepezil (E2020, Aricept) is safer. 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 9 October 2002. 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 were extracted by one reviewer (JSB ), pooled where appropriate and possible, and the weighted mean differences or Peto odds ratios (95%CI) estimated. Sixteen trials are included, involving 4365 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 unavailable. For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared with placebo (-2.02 points on the ADAS-Cog scale WMD, 95%CI -2.77 to -1.26, p<0.00001; -2.92 points on the ADAS-Cog scale WMD 95% CI -3.74 to -2.10, p<0.00001)and for 10 mg/day donepezil compared with placebo at 52 weeks (1.84MMSE points, 95% CI, 0.53 to3.15, p=0.006). The results show some improvement in global clinical state (assessed by an independent clinician) in people treated with 5 and 10 mg/day of donepezil compared with placebo at 12 and 24 weeks. Benefits of treatment were also seen on measures of activities of daily living and behaviour. 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.A variety of adverse effects were recorded, with more incidents of nausea, vomiting, diarrhoea and anorexia in the 10 mg/day group compared with placebo and the 5 mg/day group, but very few patients left a trial as a direct result of the intervention. People with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12, 24 or 52 weeks with donepezil experienced benefits in cognitive function, activities of daily living and behaviour. Study clinicians rated global clinical state more positively in treated patients, and measured less decline in measures of global disease severity. Although no significant changes were measured on a patient-rated quality of life scales, the instrument used was crude and possibly unsuited to the task. The additional data now available confirm the findings of the previous issue of this review and extend the evidence for the effectiveness of treatment to at least 52 weeks and to those with severe dementia. More evidence is still needed for the economic efficacy of donepezil, but clinical efficacy is confirmed.