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Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies.

Abstract

OBJECTIVE

Long-standing evidence indicates that Alzheimer's disease patients with behavioral symptoms have a worse prognosis and a more rapid disease progression. The current retrospective analysis evaluated the efficacy and safety of memantine in a subpopulation of patients with Alzheimer's disease exhibiting behavioral symptoms of agitation/aggression or psychosis at baseline.

METHOD

A pooled analysis was conducted in people with agitation/aggression or psychosis from 3 large 6-month, randomized studies in moderately severe to severe Alzheimer's disease. The effect of memantine and placebo on these specific symptoms was evaluated using the Neuropsychiatric Inventory (NPI) subitem cluster of agitation and psychosis. Outcomes on global, cognitive, and functional measures were also analyzed.

RESULTS

Sixty percent of the total patient group had baseline symptoms of agitation/aggression, delusions, or hallucinations on the NPI. At both 12 and 24/28 weeks, there was a significant treatment advantage for memantine over placebo for the proportion of patients showing improvement on the defined neuropsychiatric symptom cluster (55.6% vs. 44.4% at week 12, p = .008; 58.0% vs. 44.8% at week 24/28, p = .002) and specifically for the treatment of agitation/aggression (55.3% vs. 43.1% at week 12, p = .011; 61.0% vs. 45.0% at week 24/28, p < .001). Placebo-treated patients in this population demonstrated an accelerated disease progression for global (Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognitive (Severe Impairment Battery), and functional (Alzheimer Disease Cooperative Study Activities of Daily Living Inventory 19-item scale) outcomes, but memantine conferred statistically significant benefit for all measures. Tolerability in this population remained good, and fewer memantine-treated patients than placebo-treated patients withdrew due to adverse events.

CONCLUSIONS

This post hoc analysis provides important evidence from placebo-controlled trials that memantine may be a safe and effective treatment in Alzheimer's disease patients with agitation/aggression or psychosis, who are otherwise prone to rapid progression. Memantine treatment provided benefits in cognitive, functional, and global outcomes in these patients and for their agitation/aggression.

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  • Authors+Show Affiliations

    ,

    From the Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Headington, UK. Gordon.Wilcock@ndm.ox.ac.uk

    , ,

    Source

    The Journal of clinical psychiatry 69:3 2008 Mar pg 341-8

    MeSH

    Aged
    Aggression
    Alzheimer Disease
    Delusions
    Dopamine Agents
    Female
    Hallucinations
    Humans
    Male
    Memantine
    Population Surveillance
    Psychiatric Status Rating Scales
    Psychomotor Agitation
    Randomized Controlled Trials as Topic
    Retrospective Studies
    Severity of Illness Index
    Surveys and Questionnaires
    Treatment Outcome

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    18294023

    Citation

    Wilcock, Gordon K., et al. "Memantine for Agitation/aggression and Psychosis in Moderately Severe to Severe Alzheimer's Disease: a Pooled Analysis of 3 Studies." The Journal of Clinical Psychiatry, vol. 69, no. 3, 2008, pp. 341-8.
    Wilcock GK, Ballard CG, Cooper JA, et al. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008;69(3):341-8.
    Wilcock, G. K., Ballard, C. G., Cooper, J. A., & Loft, H. (2008). Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. The Journal of Clinical Psychiatry, 69(3), pp. 341-8.
    Wilcock GK, et al. Memantine for Agitation/aggression and Psychosis in Moderately Severe to Severe Alzheimer's Disease: a Pooled Analysis of 3 Studies. J Clin Psychiatry. 2008;69(3):341-8. PubMed PMID: 18294023.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. AU - Wilcock,Gordon K, AU - Ballard,Clive G, AU - Cooper,James A, AU - Loft,Henrik, PY - 2008/2/26/pubmed PY - 2008/5/23/medline PY - 2008/2/26/entrez SP - 341 EP - 8 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 69 IS - 3 N2 - OBJECTIVE: Long-standing evidence indicates that Alzheimer's disease patients with behavioral symptoms have a worse prognosis and a more rapid disease progression. The current retrospective analysis evaluated the efficacy and safety of memantine in a subpopulation of patients with Alzheimer's disease exhibiting behavioral symptoms of agitation/aggression or psychosis at baseline. METHOD: A pooled analysis was conducted in people with agitation/aggression or psychosis from 3 large 6-month, randomized studies in moderately severe to severe Alzheimer's disease. The effect of memantine and placebo on these specific symptoms was evaluated using the Neuropsychiatric Inventory (NPI) subitem cluster of agitation and psychosis. Outcomes on global, cognitive, and functional measures were also analyzed. RESULTS: Sixty percent of the total patient group had baseline symptoms of agitation/aggression, delusions, or hallucinations on the NPI. At both 12 and 24/28 weeks, there was a significant treatment advantage for memantine over placebo for the proportion of patients showing improvement on the defined neuropsychiatric symptom cluster (55.6% vs. 44.4% at week 12, p = .008; 58.0% vs. 44.8% at week 24/28, p = .002) and specifically for the treatment of agitation/aggression (55.3% vs. 43.1% at week 12, p = .011; 61.0% vs. 45.0% at week 24/28, p < .001). Placebo-treated patients in this population demonstrated an accelerated disease progression for global (Clinician's Interview-Based Impression of Change Plus Caregiver Input), cognitive (Severe Impairment Battery), and functional (Alzheimer Disease Cooperative Study Activities of Daily Living Inventory 19-item scale) outcomes, but memantine conferred statistically significant benefit for all measures. Tolerability in this population remained good, and fewer memantine-treated patients than placebo-treated patients withdrew due to adverse events. CONCLUSIONS: This post hoc analysis provides important evidence from placebo-controlled trials that memantine may be a safe and effective treatment in Alzheimer's disease patients with agitation/aggression or psychosis, who are otherwise prone to rapid progression. Memantine treatment provided benefits in cognitive, functional, and global outcomes in these patients and for their agitation/aggression. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/18294023/Memantine_for_agitation/aggression_and_psychosis_in_moderately_severe_to_severe_Alzheimer's_disease:_a_pooled_analysis_of_3_studies_ L2 - http://www.psychiatrist.com/jcp/article/pages/2008/v69n03/v69n0302.aspx DB - PRIME DP - Unbound Medicine ER -