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Efficacy of Donepezil on Behavioral Symptoms in Patients With Moderate to Severe Alzheimer's Disease

  • Serge Gauthier (a1), Howard Feldman (a2), Jane Hecker (a3), Bruno Vellas (a4), David Ames (a5), Ponni Subbiah (a6), Edward Whalen (a7) and Birol Emir (a8)
  • DOI:
  • Published online: 01 December 2002

Objective: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. Methods: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5–17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiaric Inventory (NPI). Results: Baseline demographics were similar between the treatment groups. Least squares mean (± SE) baseline NPI 12-item total scores were 19.55 ± 1.48 and 19.30 ± 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). Conclusions: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.

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International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
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