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A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.

Abstract

OBJECTIVE
To investigate the efficacy and safety of donepezil in patients with moderate to severe AD (standardized Mini-Mental State Examination [sMMSE] scores of 5 to 17; Functional Assessment Staging score < or =6 at baseline).
METHODS
Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+).
RESULTS
Patients' mean age was 73.6 years (range 48 to 92 years). Baseline demographics were similar between the treatment groups. Least squares (LS) mean +/- SE sMMSE scores at baseline were 11.7 +/- 0.35 for the donepezil group and 12.0 +/- 0.34 for the placebo group. Patients receiving donepezil showed benefits on the CIBIC+, compared with placebo, at all visits up to week 24 (p < 0.001) and at week 24 last observation carried forward (LOCF) (p < 0.0001). All other secondary measures (including sMMSE, Severe Impairment Battery, Disability Assessment for Dementia, Functional Rating Scale, and Neuropsychiatric Inventory) showed significant differences between the groups in favor of donepezil at week 24 LOCF. Eighty-four percent of donepezil- and 86% of placebo-treated patients completed the trial. Adverse events (AE) were experienced by 83% of donepezil- and 80% of placebo-treated patients, the majority of which were rated mild in severity; 8% of donepezil- and 6% of placebo-treated patients discontinued because of AE. Laboratory and vital sign abnormalities were similar between the treatment groups.
CONCLUSION
These data suggest that donepezil's benefits extend into more advanced stages of AD than those previously investigated, with very good tolerability.

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  • Publisher Full Text
  • Authors

    Feldman H, Gauthier S, Hecker J, Vellas B, Subbiah P, Whalen E, Donepezil MSAD Study Investigators Group

    Source

    Neurology 57:4 2001 Aug 28 pg 613-20

    MeSH

    Activities of Daily Living
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Analysis of Variance
    Cholinesterase Inhibitors
    Cognition
    Double-Blind Method
    Female
    Humans
    Indans
    Least-Squares Analysis
    Male
    Middle Aged
    Neuropsychological Tests
    Piperidines
    Severity of Illness Index
    Treatment Outcome

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    11524468