Oral Session O1-05 - Therapeutics - 1

Sunday, July 18, 2004

Abstract: O1-05-07

Citation: NeuroBiology of Aging, Volume 25, Number S2 , July 2004, Page 20

Behavioral Benefits with Continued Donepezil Treatment in Alzheimer's Disease Patients

P. Johannsen1, R. Holub2, G. Jakab3, S. Jakobsen4, C.J. Kalisvaart5, W. Kozubski6, A. Kurz7, E. Triau8, M. Tsolaki9, L. Bergendorff10, Y. Xu11, N. Kumar11, S. Richardson12

1 Rigshospitalet, Copenhagen, Denmark; 2 Neurological Association of Albany PC, Albany, NY, USA; 3 Uzsoki Street Hospital of Budapest Municipality, Budapest, Hungary; 4 Department of Geriatrics, Sygehus Fyn, Rudkøbing, Denmark; 5 Medisch Centrum Alkmaar, Alkmaar, Netherlands; 6 University School of Medicine, Poznan, Poland; 7 Technical University of Munich, Munich, Germany; 8 Neurologie Centrum Leuven, Leuven, Belgium; 9 Peripheral General Hospital of Thessaloniki ``Papanikolaou'', Thessaloniki, Greece; 10 Pfizer Denmark, Ballerup, Denmark; 11 Pfizer Inc, New York, NY, USA; 12 Eisai Inc, Teaneck, NJ, USA. Contact e-mail: rsutch@ppsiuk.com

Background: Donepezil provides benefits across the severity spectrum of Alzheimer's disease (AD), including for behavioral symptoms, but is often discontinued in patients whose cognition declines. Objective: To examine the behavioral benefits of continued treatment in AD patients who, during initial therapy, showed uncertain benefit as assessed by cognition and global impression. Methods: The AWARE (Aricept® WAshout and REchallenge) study enrolled patients with mild to moderate AD and included a 24-week, open-label donepezil (10 mg/day) treatment phase, a 12-week, randomized, double-blind phase (continued donepezil or placebo) for patients showing uncertain benefit, and a 12-week, single-blind donepezil treatment phase. Patients were classified as showing uncertain clinical benefit during the open-label phase if they exhibited decline or no change on the MMSE and the physician's global impression indicated a lack of sufficient certainty of clinical benefit to continue treatment. Behavior during double-blind treatment was assessed on the Neuropsychiatric Inventory (NPI). Results are reported for intent-to-treat observed cases. Results: Following open-label treatment, patients showing uncertain benefit (n = 202) were randomized to receive donepezil (n = 99) or placebo washout (n = 103). NPI scores ranged from 0-50 at baseline. Behavioral symptoms improved in patients receiving continued donepezil, compared with decline in patients receiving placebo, and this difference was significant (least-squares mean change from NPI baseline score at Week 12: donepezil, -2.40 0.98; placebo, 0.76 1.03; P=0.017). Conclusions: AD patients who continued on donepezil demonstrated behavioral benefits over those who switched to placebo, reaching statistical significance at 12 weeks. Behavioral symptoms should therefore be considered an important clinical outcome measure when evaluating treatment responses in AD patients.