The quality of evidence is downgraded by indirectness of evidence (short follow-up, surrogate outcomes).
A treatment attempt with donepezil is recommended for improving cognitive function, activities of daily living and global assessment in Alzheimer's disease.
The recommendation is strong because of possible positive effect on cognitive function, activities of daily living and global assessment. The cost of donepezil is low.
A Cochrane review [Abstract] 1 included 30 trials (8257 participants) of which 28 with sufficient details to be included in the meta-analyses. Most trials were of 6 months or less duration in selected patients. The studies tested mainly donepezil capsules at a dose of 5 mg/day or 10 mg/day. Participants in 21 studies had mild to moderate disease, in 5 studies moderate to severe, and in 4 severe disease. Most side effects were described as mild. Nausea, vomiting and diarrhoea were the most common side effects.
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk/ Placebo | Corresponding risk/Donepezil 10 mg/day | |||||
| Cognitive function (change from baseline at 26 weeks using ADAS-Cog) | The mean score in the donepezil group was 2.67 lower (3.31 to 2.02 lower) than in the placebo group | 1130 (5 studies) | moderate | ADAS-Cog score has a maximum of 70 points, the lower score in the donepezil group indicates greater improvement | ||
| Cognitive function (change from baseline at 26 weeks using MMSE) | The mean score in the donepezil group was 1.05 higher (0.73 to 1.37 higher) than in the placebo group | 1757 (7 studies) | moderate | MMSE has a maximum score of 30 points, a lower score indicates greater impairment. Treatment effect was in favour of donepezil. | ||
| Activities of daily living (change from baseline at 26 weeks measured using the ADCS) | The mean score in the intervention group was 1.03 higher (0.21 to 1.85 higher) than in the placebo group | 733 (3 studies) | moderate | Score 0-54, higher score indicates greater improvement. | ||
| Clinician-rated global impression tests (improved compared with baseline, measured using CIBIC-plus at 24-26 weeks) | 331 per 1000 | 487 per 1000 (432 to 542) | OR 1.92 (1.54 to 2.39) | 1674 (6 studies) | moderate | |
| Behavioural symptoms (change from baseline at 26 weeks measured using the NPI) | The mean score in the intervention group was 1.62 lower (3.43 lower to 0.19 higher) than in the placebo group | 1035 (4 studies) | moderate | A lower score indicates greater improvement. There was no significant difference between the 2 groups | ||
| Incidence of adverse events (at least one adverse event by 26 weeks) | 780 per 1000 | 849 per 1000 (822 to 874) | OR 1.59 (1.31 to 1.95) | 2500 (10 studies) | moderate | Adverse events were significantly more frequent in the donepezil group compared with placebo group |
Although the clinical benefits in the included studies were small, a treatment attempt is warranted due to the debilitating nature of the disease and its impact on the patient's quality of life.
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