A large, community-based, open-label trial of donepezil in the treatment of Alzheimer's disease.

This phase III trial was conducted to evaluate the safety and efficacy of donepezil in Alzheimer's disease (AD) patients with a greater range of comorbid conditions and concomitant medication use than those previously evaluated in placebo-controlled studies. Patients (n = 1,035) with mild to moderate probable or possible AD were enrolled from 255 sites in the USA; 894 (86%) completed the trial. Mean age was 74.9 years (+/- 7.8); baseline standardized Mini-Mental State Examination (sMMSE) score was 19.77 (+/- 5.4). Nearly all patients had at least 1 prior or comorbid medical condition (97%) or were taking at least 1 concomitant medication (93%). Safety assessments included recording treatment-emergent adverse events (AEs). To confirm comparability with past studies, efficacy was measured using the sMMSE. Over the 12-week study period, the mean sMMSE score increased by 1.54 points over baseline (p < 0.0001) in donepezil-treated patients. Most AEs (64%) were mild, and the occurrence of cholinergic-induced AEs was significantly lower after a dose increase at 4 weeks than that seen with a dose increase after 1 week in previous trials. Risk ratios for gastrointestinal side effects were not significantly increased by the use of aspirin or nonsteroidal anti-inflammatory drugs. Risk ratios for bradycardia were not significantly increased by the use of beta-blockers, nondihydropyridine calcium channel blockers or digoxin. Therefore, donepezil improved cognition, as measured by the sMMSE, and was well tolerated despite high concomitant medication use and extensive comorbidity. These results highlight donepezil as a safe and effective treatment for AD patients typically seen by community-based physicians. Copyright 2003 S. Karger AG, Basel