Dataset Information

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

ABSTRACT:

Background

The risk-benefit relationship of memantine treatment for Alzheimer's disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates.

Methods

A systematic review and meta-analysis of double-blind, placebo controlled clinical trials was performed. Primary outcomes were all-cause discontinuation, discontinuation due to adverse events (AE) and efficacy on cognitive function. Odds ratio (OR) and standard mean difference (SMD) with 95% confidence intervals were calculated. Meta-regression was conducted to identify related covariates. Cochrane Collaboration tool was used to evaluate the risk of bias of included trials.

Results

Eighteen studies involving 5004 patients were included. No differences between memantine and placebo were found for all-cause treatment discontinuation (OR=0.97 [0.82, 1.14]) and discontinuation due to AE (OR=1.18 [0.91, 1.53]). Memantine showed small improvement on cognitive function (SMD=0.15 [0.08, 0.22]). Baseline functional ability was positively associated with all-cause treatment discontinuation and discontinuation due to AE.

Conclusions

Our study suggests that memantine has a very small efficacy on AD symptomatology and its safety profile is similar to that of placebo. No evidence of treatment discontinuation improvement with memantine is found, indicating a dubious risk-benefit relationship. No intervention characteristic or subgroup of patients clearly shows a significantly better risk-benefit relationship.

Prospero registration

CRD42014015696 .

SUBMITTER: Blanco-Silvente L

PROVIDER: S-EPMC6057050 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

Blanco-Silvente Lídia L Capellà Dolors D Garre-Olmo Josep J Vilalta-Franch Joan J Castells Xavier X

BMC geriatrics 20180724 1

<h4>Background</h4>The risk-benefit relationship of memantine treatment for Alzheimer's disease (AD) remains unclear. In addition, variability between the results of clinical trials has been observed. The aim of this study was to investigate the risk-benefit relationship of memantine treatment in patients with AD and to determine the predictor effect of patient, intervention, and study design related covariates.<h4>Methods</h4>A systematic review and meta-analysis of double-blind, placebo contro ...[more]

PMID: 30041625

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Project description:BackgroundWe performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).MethodsThe 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.ResultsNine 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.ConclusionsMemantine 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.

Project description:BackgroundMemantine is effective in the treatment of behavioral disturbances in patients with Alzheimer's disease. It has not yet been fully determined which behavioral disturbances respond best to memantine.MethodsWe conducted a meta-analysis of memantine vs control (placebo or usual care) for the treatment of individual behavioral disturbances (delusion, hallucination, agitation/aggression, dysphoria, anxiety/phobia, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity/activity disturbances, nighttime disturbance/diurnal rhythm disturbances, and eating disturbances). Randomized controlled studies of memantine in patients with Alzheimer's disease were included in this study. To evaluate these outcomes, standardized mean difference (SMD), with 95% confidence intervals (95% CIs), based upon a random-effects model was evaluated in the meta-analysis.ResultsA total of 11 studies (n=4,261; memantine vs placebo: N=4, n=1,500; memantine + cholinesterase inhibitors [M + ChEIs] vs ChEIs: N=7, n=2,761) were included in the meta-analysis. Compared to control, memantine showed significant improvement in agitation/aggression (SMD =-0.11; 95% CIs =-0.20, -0.03; P=0.01; I2=47%), delusion (SMD =-0.12; 95% CIs =-0.18, -0.06; P=0.0002; I2=0%), disinhibition (SMD =-0.08; 95% CIs =-0.15, -0.00; P=0.04; I2=0%), and nighttime disturbance/diurnal rhythm disturbances (SMD =-0.10; 95% CIs =-0.18, -0.02; P=0.02; I2=36%). Memantine was also marginally superior to control in hallucination (SMD =-0.06; 95% CIs =-0.12, 0.01; P=0.07; I2=0%) and irritability/lability (SMD =-0.09; 95% CIs =-0.19, 0.01; P=0.07; I2=42%). Memantine is similar to control in dysphoria, anxiety/phobia, euphoria, apathy, and eating disturbance.ConclusionThe meta-analysis suggest that memantine has benefits for the treatment of most of the behavioral disturbances in patients with Alzheimer's disease. Memantine does not deteriorate negative symptoms as behavioral disturbances in patients with Alzheimer's disease.

Dataset Information

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

Background

Methods

Results

Conclusions

Prospero registration

Publications

Predictors of discontinuation, efficacy, and safety of memantine treatment for Alzheimer's disease: meta-analysis and meta-regression of 18 randomized clinical trials involving 5004 patients.

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