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

Chris Fox, Monica Crugel, Ian Maidment, Bjorn H. Auestad, Simon Coulton, Adrian Treloar, Clive Ballard, Malaz Boustani, Cornelius Katona, Gill Livingston

Research output: Contribution to journalArticle

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.
LanguageEnglish
Article numbere35185
Number of pages8
JournalPLoS ONE
Volume7
Issue number5
DOIs
Publication statusPublished - 2 May 2012

Fingerprint

Memantine
dementia
agitation
placebos
Alzheimer Disease
Placebos
Equipment and Supplies
signs and symptoms (animals and humans)
global change
Pharmacology
Home Care Services
distress
Cognition
Caregivers
Antipsychotic Agents
quality of life
cognition
morbidity
Randomized Controlled Trials
Quality of Life

Bibliographical note

© 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.

Cite this

Fox, Chris ; Crugel, Monica ; Maidment, Ian ; Auestad, Bjorn H. ; Coulton, Simon ; Treloar, Adrian ; Ballard, Clive ; Boustani, Malaz ; Katona, Cornelius ; Livingston, Gill. / Efficacy of memantine for agitation in Alzheimer's dementia : a randomised double-blind placebo controlled trial. In: PLoS ONE. 2012 ; Vol. 7, No. 5.
@article{fd9c2faa54d242dfb60535f2d56c1cfd,
title = "Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial",
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.",
author = "Chris Fox and Monica Crugel and Ian Maidment and Auestad, {Bjorn H.} and Simon Coulton and Adrian Treloar and Clive Ballard and Malaz Boustani and Cornelius Katona and Gill Livingston",
note = "{\circledC} 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.",
year = "2012",
month = "5",
day = "2",
doi = "10.1371/journal.pone.0035185",
language = "English",
volume = "7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

Fox, C, Crugel, M, Maidment, I, Auestad, BH, Coulton, S, Treloar, A, Ballard, C, Boustani, M, Katona, C & Livingston, G 2012, 'Efficacy of memantine for agitation in Alzheimer's dementia: a randomised double-blind placebo controlled trial' PLoS ONE, vol. 7, no. 5, e35185. https://doi.org/10.1371/journal.pone.0035185

Efficacy of memantine for agitation in Alzheimer's dementia : a randomised double-blind placebo controlled trial. / Fox, Chris; Crugel, Monica; Maidment, Ian; Auestad, Bjorn H.; Coulton, Simon; Treloar, Adrian; Ballard, Clive; Boustani, Malaz; Katona, Cornelius; Livingston, Gill.

In: PLoS ONE, Vol. 7, No. 5, e35185, 02.05.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy of memantine for agitation in Alzheimer's dementia

T2 - PLoS ONE

AU - Fox, Chris

AU - Crugel, Monica

AU - Maidment, Ian

AU - Auestad, Bjorn H.

AU - Coulton, Simon

AU - Treloar, Adrian

AU - Ballard, Clive

AU - Boustani, Malaz

AU - Katona, Cornelius

AU - Livingston, Gill

N1 - © 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.

PY - 2012/5/2

Y1 - 2012/5/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84860509122&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0035185

DO - 10.1371/journal.pone.0035185

M3 - Article

VL - 7

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 5

M1 - e35185

ER -