Memantine monotherapy for Alzheimer's Disease:A systematic review and meta-analysis

Shinji Matsunaga, Taro Kishi, Nakao Iwata

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Background: We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). Methods: The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes. Results: Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI= -0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17≠ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups. Conclusions: Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.

Original languageEnglish
Article numbere0123289
JournalPloS one
Volume10
Issue number4
DOIs
Publication statusPublished - 10-04-2015

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Memantine
systematic review
Alzheimer disease
meta-analysis
Meta-Analysis
confidence interval
Alzheimer Disease
placebos
Confidence Intervals
cognition
dementia
Cognition
Placebos
Activities of Daily Living
Dementia
agitation
relative risk
adverse effects
cholinesterase inhibitors
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

@article{f5d5d8001a5940689ace5300cb179f9e,
title = "Memantine monotherapy for Alzheimer's Disease:A systematic review and meta-analysis",
abstract = "Background: We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). Methods: The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes. Results: Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95{\%} confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95{\%} CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95{\%} CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95{\%} CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95{\%} CI= -0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95{\%} CI=0.17≠ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95{\%} CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups. Conclusions: Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.",
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Memantine monotherapy for Alzheimer's Disease:A systematic review and meta-analysis. / Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao.

In: PloS one, Vol. 10, No. 4, e0123289, 10.04.2015.

Research output: Contribution to journalArticle

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AU - Matsunaga, Shinji

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AU - Iwata, Nakao

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N2 - Background: We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). Methods: The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes. Results: Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI= -0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17≠ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups. Conclusions: Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.

AB - Background: We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). Methods: The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes. Results: Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI= -0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17≠ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups. Conclusions: Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.

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