The effects of donepezil in Alzheimer's disease - Results from a multinational trial

Donepezil has been shown to be well tolerated and to improve cognition and global function in patients with mild to moderately severe Alzheimer's dise ase (AD). The current trial was undertaken to investigate further the effic acy and safety of donepezil, in a multinational setting, in patients with m ild to moderately severe AD. This 30-week, placebo-controlled, parallel-gro up study consisted of a 24-week, double-blind treatment phase followed by a 6-week, single-blind, placebo washout. Eight hundred and eighteen patients with mild to moderately severe AD were randomly allocated to treatment wit h single, daily doses of 5 or 10 mg donepezil, or placebo. The two primary efficacy measures were: a cognitive performance test, the Alzheimer's Disea se Assessment Scale-cognitive subscale (ADAS-cog) and a global evaluation, the Clinician's Interview-Based Impression of Change with caregiver input ( CIBIC plus). Secondary outcome measures included the Sum of the Boxes of th e Clinical Dementia Rating Scale (CDR-SB), a modified Interview for Deterio ration in Daily living activities in Dementia (IDDD) and a patient-rated qu ality of life assessment. Statistically significant improvements in cogniti ve and global function were observed, as evaluated by ADAS-cog and CIBIC pl us, respectively, in both the 5 and 10 mg/day donepezil groups, compared wi th placebo. Treatment-associated changes were also observed in functional s kills, as shown by improved scores on the CDR-SB and the complex-tasks comp onent of the IDDD. A dose-response effect was evident, with the 10 mg/day d onepezil group demonstrating greater benefits in all outcome measures than the 5 mg/day group. Donepezil was well tolerated by this patient population and did not produce any clinically significant laboratory test abnormaliti es. The results of this study confirm that donepezil is effective and well tolerated in treating the symptoms of mild to moderately severe AD.