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Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study.

Abstract

BACKGROUND

The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimer's disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living.

METHODS

We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimer's disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for patients with data at baseline and at one or more other timepoints (modified intent-to-treat population) with last observation carried forward used to replace missing data.

FINDINGS

95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in SIB scores and declined less in ADCS-ADL-severe scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n=20) than in the placebo group (n=8).

INTERPRETATION

Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Karolinska Institutet, Alzheimer's Disease Research Center, Department of Neurotec, Division of Geriatric Medicine, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden. Electronic address: bengt.winblad@ki.se.

    ,

    Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden.

    ,

    Section of Geriatric Medicine, Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden.

    ,

    Clinical Memory Research Unit, Department of Clinical Sciences, Malmö Lund University, Malmö, Sweden.

    ,

    Department of Primary Care, Kalix Vårdcentral, Kalix, Sweden.

    ,

    Pfizer AB, PO Box 501, Täby, Sweden.

    ,

    Pfizer AB, PO Box 501, Täby, Sweden.

    ,

    Pfizer AB, PO Box 501, Täby, Sweden.

    Source

    Lancet (London, England) 367:9516 2006 Apr 01 pg 1057-1065

    MeSH

    Activities of Daily Living
    Alzheimer Disease
    Cholinesterase Inhibitors
    Cognition
    Donepezil
    Double-Blind Method
    Humans
    Indans
    Middle Aged
    Nursing Homes
    Piperidines
    Severity of Illness Index

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    16581404

    Citation

    Winblad, Bengt, et al. "Donepezil in Patients With Severe Alzheimer's Disease: Double-blind, Parallel-group, Placebo-controlled Study." Lancet (London, England), vol. 367, no. 9516, 2006, pp. 1057-1065.
    Winblad B, Kilander L, Eriksson S, et al. Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. Lancet. 2006;367(9516):1057-1065.
    Winblad, B., Kilander, L., Eriksson, S., Minthon, L., Båtsman, S., Wetterholm, A. L., ... Haglund, A. (2006). Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. Lancet (London, England), 367(9516), pp. 1057-1065. doi:10.1016/S0140-6736(06)68350-5.
    Winblad B, et al. Donepezil in Patients With Severe Alzheimer's Disease: Double-blind, Parallel-group, Placebo-controlled Study. Lancet. 2006 Apr 1;367(9516):1057-1065. PubMed PMID: 16581404.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Donepezil in patients with severe Alzheimer's disease: double-blind, parallel-group, placebo-controlled study. AU - Winblad,Bengt, AU - Kilander,Lena, AU - Eriksson,Sture, AU - Minthon,Lennart, AU - Båtsman,Stellan, AU - Wetterholm,Anna-Lena, AU - Jansson-Blixt,Catarina, AU - Haglund,Anders, AU - ,, PY - 2006/4/4/pubmed PY - 2006/4/14/medline PY - 2006/4/4/entrez SP - 1057 EP - 1065 JF - Lancet (London, England) JO - Lancet VL - 367 IS - 9516 N2 - BACKGROUND: The cholinesterase inhibitor donepezil is used to treat mild-to-moderate Alzheimer's disease. Its efficacy in severe dementia has not been assessed and is controversial. Our aim was to ascertain the effectiveness of donepezil in patients with severe Alzheimer's disease, by focusing primarily on cognition and activities of daily living. METHODS: We did a 6-month, double-blind, parallel-group, placebo-controlled study in 248 patients with severe Alzheimer's disease (mini mental state examination score 1-10) who were living in assisted care nursing homes ran by trained staff in Sweden. We assigned patients oral donepezil (5 mg per day for 30 days then up to 10 mg per day thereafter, n=128) or matched placebo (n=120). Our primary endpoints were change from baseline to month 6 in the severe impairment battery (SIB) and modified Alzheimer's Disease Cooperative Study activities of daily living inventory for severe Alzheimer's disease (ADCS-ADL-severe). We analysed outcomes for patients with data at baseline and at one or more other timepoints (modified intent-to-treat population) with last observation carried forward used to replace missing data. FINDINGS: 95 patients assigned donepezil and 99 patients assigned placebo completed the study. Patients treated with donepezil improved more in SIB scores and declined less in ADCS-ADL-severe scores at 6 months after initiation of treatment compared with baseline than did controls (least squares [LS] mean difference, 5.7, 95% CI 1.5-9.8; p=0.008, and 1.7, 0.2-3.2; p=0.03, respectively). The incidence of adverse events was comparable between groups (donepezil 82% [n=105] vs placebo 76% [n=91]), with most being transient and mild or moderate in severity. More patients discontinued treatment because of adverse events in the donepezil group (n=20) than in the placebo group (n=8). INTERPRETATION: Donepezil improves cognition and preserves function in individuals with severe Alzheimer's disease who live in nursing homes. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/16581404/Donepezil_in_patients_with_severe_Alzheimer's_disease:_double_blind_parallel_group_placebo_controlled_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(06)68350-5 DB - PRIME DP - Unbound Medicine ER -