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A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting.

Abstract

OBJECTIVES

To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities.

DESIGN

Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial.

SETTING

Twenty-seven nursing homes across the United States.

PARTICIPANTS

Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7.

MEASUREMENTS

The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs).

RESULTS

Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed.

CONCLUSION

Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, New York 14620, USA.

    , , , , ,

    Source

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Cholinesterase Inhibitors
    Cognition
    Donepezil
    Double-Blind Method
    Female
    Humans
    Indans
    Male
    Middle Aged
    Neuropsychological Tests
    Nursing Homes
    Outcome Assessment (Health Care)
    Piperidines
    Psychiatric Status Rating Scales
    Severity of Illness Index

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11843990

    Citation

    Tariot, P N., et al. "A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Donepezil in Patients With Alzheimer's Disease in the Nursing Home Setting." Journal of the American Geriatrics Society, vol. 49, no. 12, 2001, pp. 1590-9.
    Tariot PN, Cummings JL, Katz IR, et al. A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. J Am Geriatr Soc. 2001;49(12):1590-9.
    Tariot, P. N., Cummings, J. L., Katz, I. R., Mintzer, J., Perdomo, C. A., Schwam, E. M., & Whalen, E. (2001). A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. Journal of the American Geriatrics Society, 49(12), pp. 1590-9.
    Tariot PN, et al. A Randomized, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Donepezil in Patients With Alzheimer's Disease in the Nursing Home Setting. J Am Geriatr Soc. 2001;49(12):1590-9. PubMed PMID: 11843990.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting. AU - Tariot,P N, AU - Cummings,J L, AU - Katz,I R, AU - Mintzer,J, AU - Perdomo,C A, AU - Schwam,E M, AU - Whalen,E, PY - 2002/2/15/pubmed PY - 2002/3/8/medline PY - 2002/2/15/entrez SP - 1590 EP - 9 JF - Journal of the American Geriatrics Society JO - J Am Geriatr Soc VL - 49 IS - 12 N2 - OBJECTIVES: To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer's disease (AD) residing in nursing home facilities. DESIGN: Twenty-four-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled trial. SETTING: Twenty-seven nursing homes across the United States. PARTICIPANTS: Two hundred eight nursing home patients with a diagnosis of probable or possible AD, or AD with cerebrovascular disease; mean Mini-Mental State Examination (MMSE) score 14.4; mean age 85.7. MEASUREMENTS: The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Secondary efficacy measures were the Clinical Dementia Rating (Nursing Home Version)-Sum of the Boxes (CDR-SB), MMSE, and the Physical Self-Maintenance Scale (PSMS). Safety was monitored by physical examinations, vital signs, clinical laboratory tests, electrocardiograms (ECGs), and treatment-emergent adverse events (AEs). RESULTS: Eighty-two percent of donepezil- and 74% of placebo-treated patients completed the trial. Eleven percent of donepezil- and 18% of placebo-treated patients withdrew because of AEs. Mean NPI-NH 12-item total scores improved relative to baseline for both groups, with no significant differences observed between the groups at any assessment. Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 (P < .05). The change in CDR-SB total score was not influenced by age. Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8, 16, and 20 (P < .05). No significant differences were observed between the groups on the PSMS. Overall rates of occurrence and severity of AEs were similar between the two groups (97% placebo, 96% donepezil). Gastrointestinal AEs occurred more frequently in donepezil-treated patients. In general, AEs were similar in older and younger donepezil-treated patients, with the majority of patients experiencing only AEs that were transient and mild or moderate in severity. Weight loss was reported as an AE more frequently in older patients, although a loss at last visit of >or=7% of screening weight occurred at the same rate in older and younger patients (9% of donepezil- and 6% of placebo-treated patients). No significant differences between groups in vital sign changes, bradycardia, or rates of clinically significant laboratory or ECG abnormalities were observed. CONCLUSION: Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period. The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil. These findings also suggest that advanced age, comorbid illnesses, and high concomitant medication usage should not be barriers to donepezil treatment. Given the apparent improvement in behavior in the placebo group, and the high use of concomitant medications in both groups, the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation. In summary, effects on cognition, overall dementia severity, and safety and tolerability findings are consistent with previous findings in outpatients and support the use of donepezil in patients with AD who reside in nursing homes. SN - 0002-8614 UR - https://www.unboundmedicine.com/medline/citation/11843990/A_randomized_double_blind_placebo_controlled_study_of_the_efficacy_and_safety_of_donepezil_in_patients_with_Alzheimer's_disease_in_the_nursing_home_setting_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0002-8614&amp;date=2001&amp;volume=49&amp;issue=12&amp;spage=1590 DB - PRIME DP - Unbound Medicine ER -