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):341-348
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Objective: Longstanding 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.