A Cochrane review [Abstract] 1 included 2 studies with a total of 782 subjects. All had a MMSE greater than 23 points.
In the first study there was a significant difference between the number of patients diagnosed with AD or another dementia between the donepezil group and the placebo group in favour of donepezil after one year of treatment (16/253 donepezil, 38/259 placebo; OR 0.39, 95% CI 0.21 to 0.72, NNT=12), but no difference after 3 years of treatment (63/253 donepezil, 73/259 placebo; OR 0.84, 95% CI 0.57 to 1.25, NNT=30).
In the second study the 13-item ADAS-Cog showed a very modest benefit associated with 10 mg/day donepezil compared with placebo at 24 weeks (MD 1.90 points on a scale 0-85, 95% CI 0.51 to 3.29), but four other measures of cognitive function did not. In the donepezil group, there were more withdrawals before the end of treatment at 24 weeks (43/133 donepezil, 23/137 placebo; OR 2.37, 95% CI 1.33 to 4.22, which corresponds to 1 in 6 patients on donepezil withdrawing because of its adverse effects), withdrawals due to an adverse event (29/133 donepezil, 10/137 placebo; OR 3.54, 95% CI 1.65 to 7.60), and numbers experiencing an adverse event (116/133 donepezil, 100/137 placebo; OR 2.52 95% CI 1.34 to 4.76, NNH=7). Adverse effects included diarrhoea, nausea and vomiting, leg cramps and abnormal dreams.
Comment: The quality of evidence is downgraded by indirectness: The studies have a fairly high rate of conversion to AD over 3 years which may reflect the recruitment of subjects from clinic type populations. No conclusions can be made on the effect of treatment on quality of life. The authors conclude that there is no evidence to support the use of donepezil for patients with mild cognitive impairment (MCI), because the putative benefits are minor, short lived and associated with significant side effects.
See also evidence summary Donepezil for Alzheimer's Disease.
Primary/Secondary Keywords