Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial

dc.contributor.authorFox, Chris
dc.contributor.authorCrugel, Monica
dc.contributor.authorMaidment, Ian
dc.contributor.authorAuestad, Bjorn Henrik
dc.contributor.authorCoulton, Simon
dc.contributor.authorTreloar, Adrian
dc.contributor.authorBallard, Clive
dc.contributor.authorBoustani, Malaz
dc.contributor.authorKatona, Cornelius
dc.contributor.authorLivingston, Gill
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2025-07-03T10:36:55Z
dc.date.available2025-07-03T10:36:55Z
dc.date.issued2012
dc.description.abstractBackground: 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.
dc.eprint.versionFinal published version
dc.identifier.citationFox C, Crugel M, Maidment I, et al. Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial. PLoS One. 2012;7(5):e35185. doi:10.1371/journal.pone.0035185
dc.identifier.urihttps://hdl.handle.net/1805/49175
dc.language.isoen_US
dc.publisherPublic Library of Science
dc.relation.isversionof10.1371/journal.pone.0035185
dc.relation.journalPLoS One
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectAlzheimer disease
dc.subjectDementia
dc.subjectMemantine
dc.subjectPsychomotor agitation
dc.titleEfficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial
dc.typeArticle
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