Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial
dc.contributor.author | Fox, Chris | |
dc.contributor.author | Crugel, Monica | |
dc.contributor.author | Maidment, Ian | |
dc.contributor.author | Auestad, Bjorn Henrik | |
dc.contributor.author | Coulton, Simon | |
dc.contributor.author | Treloar, Adrian | |
dc.contributor.author | Ballard, Clive | |
dc.contributor.author | Boustani, Malaz | |
dc.contributor.author | Katona, Cornelius | |
dc.contributor.author | Livingston, Gill | |
dc.contributor.department | Medicine, School of Medicine | |
dc.date.accessioned | 2025-07-03T10:36:55Z | |
dc.date.available | 2025-07-03T10:36:55Z | |
dc.date.issued | 2012 | |
dc.description.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. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Fox 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.uri | https://hdl.handle.net/1805/49175 | |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | |
dc.relation.isversionof | 10.1371/journal.pone.0035185 | |
dc.relation.journal | PLoS One | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Alzheimer disease | |
dc.subject | Dementia | |
dc.subject | Memantine | |
dc.subject | Psychomotor agitation | |
dc.title | Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial | |
dc.type | Article |