A Cochrane review included 24 trials, involving 5 796 participants (15 trials with sufficient details to be included in the meta-analyses). Most trials were of 6 months or less duration in selected patients. For cognition there is a statistically significant improvement for both 5 and 10 mg/day of donepezil at 24 weeks compared to placebo on the ADAS-Cog scale (–2.01 points MD, 95%CI –2.69 to –1.34; –2.80 points MD, 95% CI –3.74 to –2.10, respectively) and for 10 mg/day donepezil compared with placebo at 24 weeks (5.55 SIB points, 95% CI 3.60 to 7.49) and 52 weeks (1.84 MMSE points, 95% CI 0.53 to 3.15).
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 (OR 2.38, 95% CI 1.78 to 3.19; OR 1.82, 95% CI 1.42 to 2.35). 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 (24% vs 20% placebo, OR 1.35, 95% CI 1.11 to 1.65) but not the 5 mg/day donepezil group. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. The results were similar for all severities of disease.
Authors' comment: The debate on whether donepezil is effective continues despite the evidence of efficacy from the clinical studies because the treatment effects are small and are not always apparent in practice.