Efficacy and safety of donepezil over 3 years: an open-label, multicentre study in patients with Alzheimer's disease.
OBJECTIVE
This 132-week, open-label extension study assessed the long-term efficacy and safety of donepezil in 579 patients with mild to moderate Alzheimer's disease (AD) who had previously participated in a 24-week double-blind study of 5 or 10 mg/day donepezil vs placebo.


METHODS
Patients enrolled in the present study had a 6-week single-blind placebo washout period followed by treatment with donepezil 5 mg/day for 6 weeks with an optional increase in dosage to 10 mg/day between weeks 6 and 32.


RESULTS
After 6 weeks of open-label treatment with donepezil 5 mg/day, mean Alzheimer's Disease Assessment Scale -- cognitive subscale scores (ADAS-cog) improved by approximately two points, while after 12 weeks of open-label treatment (with a majority of patients receiving 10 mg/day), the mean ADAS-cog score was 1 point better than the score at the end of the placebo washout period. Scores then declined gradually over the remainder of the study. Mean changes in Clinical Dementia Rating-Sum of Boxes scores showed slight improvement over the first 12 weeks of open-label treatment and then slowly declined for the remainder of the study period. Donepezil was well tolerated over the entire 162-week study period. Overall, 85% of patients experienced at least one adverse event (AE). The most common included diarrhoea (12%), nausea (11%), infection (11%) and accidental injury (10%). Some patients discontinued the study due to AEs (15%).


CONCLUSIONS
These results support the conclusion that donepezil is safe and effective for the long-term treatment of patients with mild to moderate AD.
Burns
A
A
University of Manchster, Manchester, UK. alistair.burns@manchester.ac.uk
Gauthier
S
S
Perdomo
C
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil