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

Chris Fox, Monica Crugel, Ian Maidment, Bjorn Henrik Auestad, Simon Coulton, Adrian Treloar, Clive Ballard, Malaz Boustani, Cornelius Katona, Gill Livingston

Research output: Contribution to journalArticle

91 Scopus citations

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. Trial Registration: ClinicalTrials.gov NCT00371059. Trial Registration: International Standard Randomised Controlled Trial 24953404.

Original languageEnglish (US)
Article numbere35185
JournalPloS one
Volume7
Issue number5
DOIs
StatePublished - May 2 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Fox, C., Crugel, M., Maidment, I., Auestad, B. H., Coulton, S., Treloar, A., Ballard, C., Boustani, M., Katona, C., & Livingston, G. (2012). Efficacy of memantine for agitation in Alzheimer's dementia: A randomised double-blind placebo controlled trial. PloS one, 7(5), [e35185]. https://doi.org/10.1371/journal.pone.0035185