Dataset Information

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.

SUBMITTER: Matsunaga S

PROVIDER: S-EPMC4393306 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis.

Matsunaga Shinji S Kishi Taro T Iwata Nakao N

PloS one 20150410 4

<h4>Background</h4>We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).<h4>Methods</h4>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 i ...[more]

PMID: 25860130

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Project description:Memantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer.To compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results.Systematic review and meta-analysis of randomised controlled trials.The Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011.Data from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine.Pooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=-0.29, 95% CI -0.45 to -0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=-0.20, 95% CI -0.31 to -0.09), cognition (SMD=-0.25, 95% CI -0.36 to -0.14) and behaviour and mood (SMD=-0.17, 95% CI -0.32 to -0.03) but not on function (SMD=-0.04, 95% CI -0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found 'no significant benefit' on any clinical measures at 1 year.These results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe.

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

Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis.

Background

Methods

Results

Conclusions

Publications

Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis.

Similar Datasets

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