title: Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial.
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.
  
  
  RESULTS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00371059.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial 24953404.
authors.affiliation: Department of Psychiatry, University of East Anglia, Norwich, United Kingdom. Chris.Fox@uea.ac.uk
authors.forename: Chris
authors.initials: C
authors.lastname: Fox
authors.forename: Monica
authors.initials: M
authors.lastname: Crugel
authors.forename: Ian
authors.initials: I
authors.lastname: Maidment
authors.forename: Bjorn Henrik
authors.initials: BH
authors.lastname: Auestad
authors.forename: Simon
authors.initials: S
authors.lastname: Coulton
authors.forename: Adrian
authors.initials: A
authors.lastname: Treloar
authors.forename: Clive
authors.initials: C
authors.lastname: Ballard
authors.forename: Malaz
authors.initials: M
authors.lastname: Boustani
authors.forename: Cornelius
authors.initials: C
authors.lastname: Katona
authors.forename: Gill
authors.initials: G
authors.lastname: Livingston
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D003704:Dementia / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D011595:Psychomotor Agitation / Q000188:drug therapy*
chemical_list: D008559:Memantine