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Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial.

Abstract

BACKGROUND

There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17).

METHODS

Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview-Based Impression of Change (CIBIC-plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment x disease severity interaction in the full MSAD study sample.

RESULTS

CIBIC-plus scores for donepezil patients were significantly improved compared with placebo for each time-point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment x severity interactions for any of the efficacy measures.

CONCLUSIONS

In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range.

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  • Authors+Show Affiliations

    ,

    Division of Neurology, University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, BC, Canada. hfeldman@interchange.ubc.ca

    , , , , , ,

    Source

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Cholinesterase Inhibitors
    Disability Evaluation
    Donepezil
    Double-Blind Method
    Female
    Humans
    Indans
    Male
    Middle Aged
    Neuropsychological Tests
    Nootropic Agents
    Piperidines
    Psychiatric Status Rating Scales
    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

    15920715

    Citation

    Feldman, Howard, et al. "Efficacy and Safety of Donepezil in Patients With More Severe Alzheimer's Disease: a Subgroup Analysis From a Randomized, Placebo-controlled Trial." International Journal of Geriatric Psychiatry, vol. 20, no. 6, 2005, pp. 559-69.
    Feldman H, Gauthier S, Hecker J, et al. Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. Int J Geriatr Psychiatry. 2005;20(6):559-69.
    Feldman, H., Gauthier, S., Hecker, J., Vellas, B., Xu, Y., Ieni, J. R., & Schwam, E. M. (2005). Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. International Journal of Geriatric Psychiatry, 20(6), pp. 559-69.
    Feldman H, et al. Efficacy and Safety of Donepezil in Patients With More Severe Alzheimer's Disease: a Subgroup Analysis From a Randomized, Placebo-controlled Trial. Int J Geriatr Psychiatry. 2005;20(6):559-69. PubMed PMID: 15920715.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Efficacy and safety of donepezil in patients with more severe Alzheimer's disease: a subgroup analysis from a randomized, placebo-controlled trial. AU - Feldman,Howard, AU - Gauthier,Serge, AU - Hecker,Jane, AU - Vellas,Bruno, AU - Xu,Yikang, AU - Ieni,John R, AU - Schwam,Elias M, AU - ,, PY - 2005/5/28/pubmed PY - 2005/10/18/medline PY - 2005/5/28/entrez SP - 559 EP - 69 JF - International journal of geriatric psychiatry JO - Int J Geriatr Psychiatry VL - 20 IS - 6 N2 - BACKGROUND: There have been very limited investigations of cholinesterase inhibitor therapy in more advanced stages of Alzheimer's disease (AD). The efficacy and safety of donepezil were evaluated in post hoc analyses of a subgroup of patients with more severe AD (standardized Mini-Mental State Examination [sMMSE] score 5-12) within a randomized, placebo-controlled trial in moderate to severe AD (MSAD study). Additional analyses examined whether donepezil's treatment effects were consistent across the full range of baseline AD severity studied (sMMSE score 5-17). METHODS: Patients with moderate to severe AD (n = 290) who were living in the community or in assisted living facilities received donepezil or placebo for 24 weeks; n = 145 in the more severe AD subgroup. The primary outcome measure was the Clinician's Interview-Based Impression of Change (CIBIC-plus) with secondary outcomes including the sMMSE, Severe Impairment Battery, Neuropsychiatric Inventory, and Disability Assessment for Dementia. Analysis of Variance and Analysis of Covariance models tested for treatment x disease severity interaction in the full MSAD study sample. RESULTS: CIBIC-plus scores for donepezil patients were significantly improved compared with placebo for each time-point, with a 0.70 mean treatment difference at Week 24 last observation carried forward (LOCF; p = 0.0002). Significant differences favoring donepezil were noted at Week 24 LOCF for all secondary measures. There were no treatment x severity interactions for any of the efficacy measures. CONCLUSIONS: In this analysis, donepezil had significant benefits over placebo on global, cognitive, functional, and behavioral measures in a subgroup of patients with more severe AD. Furthermore, the treatment effects of donepezil were not driven by a particular stratum within the moderate to severe dementia range. SN - 0885-6230 UR - https://www.unboundmedicine.com/medline/citation/15920715/Efficacy_and_safety_of_donepezil_in_patients_with_more_severe_Alzheimer's_disease:_a_subgroup_analysis_from_a_randomized_placebo_controlled_trial_ L2 - https://doi.org/10.1002/gps.1325 DB - PRIME DP - Unbound Medicine ER -