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

Fox, C; Crugel, M; Maidment, I; Auestad, BH; Coulton, S; Treloar, A; Ballard, C; ... Livingston, G; + view all (2012) Efficacy of Memantine for Agitation in Alzheimer's Dementia: A Randomised Double-Blind Placebo Controlled Trial. PLOS ONE , 7 (5) , Article e35185. 10.1371/journal.pone.0035185. Green open access

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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.

Type: Article
Title: Efficacy of Memantine for Agitation in Alzheimer's Dementia: A Randomised Double-Blind Placebo Controlled Trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0035185
Publisher version: http://dx.doi.org/10.1371/journal.pone.0035185
Language: English
Additional information: © 2012 Fox et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Lundbeck was the funder and supplied the study drug and placebo, but had no role in the study design, data collection, data analysis, study termination, data interpretation, writing or the report, or the decision to submit for publication. This work was funded by Lundbeck. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. CF has received speaker’s fees and support from Pfizer, Eisai, Novartis, Shires, and Lilly. MC was the research fellow for the MAGD study. IM has received consultancy fees and honoraria from pharmaceutical companies that include Lundbeck, Lilly, Schwarz, Pfizer, Shires, and Novartis. AT has received funding to attend educational meetings and conferences from Eisai and Pfizer and research grant from Pfizer. CB has received research grants, honoraria and consultancy fees from Lundbeck, and has received honoraria from Novartis. MB has received research funding from Forest, research funding and honoraria for advisory board membership from Novartis, and speaker’s fees and honoraria for advisory board membership from Pfizer and Eisai. CK’s institution has received research funding from Lundbeck; he has received honoraria, support for travel, lecture fees, and payment from advisory board membership from Lundbeck and Lilly and payment for preparation of educational material from Lundbeck. GL has received research funding and educational support from Lundbeck and research funding from Pfizer. SC declares no conflicts of interest. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/1376499
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