Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial

Fox, Chris, Crugel, Monica, Maidment, Ian, Auestad, Bjorn H., Coulton, Simon, Treloar, Adrian, Ballard, Clive, Boustani, Malaz, Katona, Cornelius and Livingston, Gill (2012). Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial. PLoS ONE, 7 (5),

Abstract

Background - Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings - We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions - Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.

Publication DOI: https://doi.org/10.1371/journal.pone.0035185
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: © 2012 Fox et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords: Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
Full Text Link: http://www.plos ... al.pone.0035185
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2012-05-02
Authors: Fox, Chris
Crugel, Monica
Maidment, Ian ( 0000-0003-4152-9704)
Auestad, Bjorn H.
Coulton, Simon
Treloar, Adrian
Ballard, Clive
Boustani, Malaz
Katona, Cornelius
Livingston, Gill

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