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

Fox, Christopher, Crugel, Monica, Maidment, Ian D., Auestad, Bjorn Henrik, Coulton, Simon, Treloar, Adrian, Ballard, Clive G., Boustani, Malaz, Katona, Cornelius, Livingston, Gill and others. (2012) Efficacy of Memantine for Agitation in Alzheimer’s Dementia: A Randomised Double-Blind Placebo Controlled Trial. PLoS ONE, 7 (5). ISSN 1932-6203. (doi:10.1371/journal.pone.0035185) (KAR id:29466)

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http://dx.doi.org/10.1371/journal.pone.0035185

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.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0035185
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine > RA421 Public health. Hygiene. Preventive Medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Divisions > Division for the Study of Law, Society and Social Justice > School of Social Policy, Sociology and Social Research > Centre for Health Services Studies
Depositing User: Tony Rees
Date Deposited: 15 May 2012 13:04 UTC
Last Modified: 16 Feb 2021 12:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/29466 (The current URI for this page, for reference purposes)
Coulton, Simon: https://orcid.org/0000-0002-7704-3274
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