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Randomized Controlled Trial
. 2012;7(5):e35185.
doi: 10.1371/journal.pone.0035185. Epub 2012 May 2.

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial

Chris Fox  1 , Monica Crugel, Ian Maidment, Bjorn Henrik Auestad, Simon Coulton, Adrian Treloar, Clive Ballard, Malaz Boustani, Cornelius Katona, Gill Livingston
Affiliations
Randomized Controlled Trial

Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial

Chris Fox et al. PLoS One. 2012.

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.

Trial registration: ClinicalTrials.gov NCT00371059.

Trial registration: International Standard Randomised Controlled Trial 24953404.

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Conflict of interest statement

Competing Interests: 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.

Figures

Figure 1
Figure 1. CONSORT STATEMENT.
Figure 2
Figure 2. Mean (+/−95% confidence intervals) total CMAI by time and by group.
Circles are individual data points; red: memantine, blue: placebo.
Figure 3
Figure 3. Mean (+/−95% Confidence intervals) total NPI by time and by group.
See this image and copyright information in PMC

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