Long-term efficacy and safety of donepezil in the treatment of Alzheimer'sdisease: final analysis of a US multicentre open-label study

This multicentre, open-label study evaluated the long-term efficacy and saf ety of donepezil in the treatment of patients with mild to moderately sever e Alzheimer's disease (AD). The 133 patients who entered the study had prev iously completed a 14-week randomized, double-blind, placebo-controlled stu dy with donepezil. In this open-label study, patients were treated initiall y with 3 mg per day donepezil, which could be increased to 5, 7 and 10 mg p er day in a step-wise fashion. Patients attended the clinic for assessments at 3-week intervals for the first 12 weeks, then subsequently at 12-week i ntervals for up to 240 weeks (254 cumulative weeks). Efficacy was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog ) and the Clinical Dementia Rating-Sum of the Boxes scale (CDR-SB), and dat a were compared with those predicted for historical untreated AD patients. During the first 6-9 months of the study, mean ADAS-cog and CDR-SB scores s howed evidence of clinical improvement from baseline. After this rime score s gradually deteriorated. Overall the decline was less than that estimated if this cohort of patients had not been treated. The most common adverse ev ents were related to the nervous and digestive systems, and were generally mild and transient, resolving without the need for dose modifications. Ther e was no evidence of hepatotoxicity. In conclusion, these data demonstrate that donepezil is a well-tolerated, realistic symptomatic treatment for AD over a period of up to 4.9 years. An interim report of the first 98 weeks o f the study has been published previously. (C) 2000 Elsevier Science B.V. A ll rights reserved.