Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis
Shinji Matsunaga1, Taro Kishi1, Nakao Iwata1
1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
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.
Insights
Memantine monotherapy offers modest improvements in cognitive function and behavior for Alzheimer's disease (AD) patients. While generally well-tolerated, the clinical benefit is limited by small effect sizes.
Area of Science:
- Neurology
- Pharmacology
- Geriatrics
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
- Memantine is a medication used to manage AD symptoms.
- Previous studies on memantine monotherapy have yielded varied results.
Purpose of the Study:
- To conduct an updated meta-analysis of randomized placebo-controlled trials.
- To evaluate the efficacy and safety of memantine monotherapy in AD patients.
- To specifically exclude trials involving concomitant cholinesterase inhibitor use.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials.
- Included trials focused on memantine monotherapy versus placebo.
- Compared outcomes including cognitive function, daily living activities, behavioral disturbances, global function, dementia stage, discontinuation rates, and side effects.
Main Results:
- Nine studies with 2433 patients were analyzed.
- Memantine monotherapy showed statistically significant improvements in cognition, behavior, daily living activities, global function, and dementia stage.
- Memantine was associated with reduced discontinuation due to inefficacy and less agitation, with no significant differences in overall adverse events.
Conclusions:
- Memantine monotherapy demonstrates benefits in cognitive, behavioral, and functional domains for AD patients.
- The drug is generally well-tolerated, with reduced agitation observed.
- The clinical significance of these improvements is limited due to small effect sizes.
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