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Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial.

Abstract

CONTEXT

Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.

OBJECTIVE

To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.

DESIGN, SETTING, AND PARTICIPANTS

A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial.

INTERVENTIONS

Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n = 203) or placebo (n = 201) for 24 weeks.

MAIN OUTCOME MEASURES

Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale).

RESULTS

The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively.

CONCLUSIONS

In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry, University of Rochester Medical Center, Monroe Community Hospital, Rochester, NY 14620, USA. pierre_tariot@urmc.rochester.edu

    , , , , ,

    Source

    JAMA 291:3 2004 Jan 21 pg 317-24

    MeSH

    Aged
    Alzheimer Disease
    Cholinesterase Inhibitors
    Donepezil
    Dopamine Agents
    Double-Blind Method
    Drug Therapy, Combination
    Excitatory Amino Acid Antagonists
    Female
    Humans
    Indans
    Male
    Memantine
    Neuropsychological Tests
    Nootropic Agents
    Piperidines
    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

    14734594

    Citation

    Tariot, Pierre N., et al. "Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil: a Randomized Controlled Trial." JAMA, vol. 291, no. 3, 2004, pp. 317-24.
    Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317-24.
    Tariot, P. N., Farlow, M. R., Grossberg, G. T., Graham, S. M., McDonald, S., & Gergel, I. (2004). Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA, 291(3), pp. 317-24.
    Tariot PN, et al. Memantine Treatment in Patients With Moderate to Severe Alzheimer Disease Already Receiving Donepezil: a Randomized Controlled Trial. JAMA. 2004 Jan 21;291(3):317-24. PubMed PMID: 14734594.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. AU - Tariot,Pierre N, AU - Farlow,Martin R, AU - Grossberg,George T, AU - Graham,Stephen M, AU - McDonald,Scott, AU - Gergel,Ivan, AU - ,, PY - 2004/1/22/pubmed PY - 2004/1/30/medline PY - 2004/1/22/entrez SP - 317 EP - 24 JF - JAMA JO - JAMA VL - 291 IS - 3 N2 - CONTEXT: Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed. OBJECTIVE: To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial. INTERVENTIONS: Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n = 203) or placebo (n = 201) for 24 weeks. MAIN OUTCOME MEASURES: Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL19). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale). RESULTS: The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P<.001); ADCS-ADL19 (possible score range, 0-54), -2.0 (0.50) vs -3.4 (0.51), respectively (P =.03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P =.03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively. CONCLUSIONS: In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/14734594/Memantine_treatment_in_patients_with_moderate_to_severe_Alzheimer_disease_already_receiving_donepezil:_a_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.291.3.317 DB - PRIME DP - Unbound Medicine ER -