Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis
Taro Kishi1, Shinji Matsunaga1, Kazuto Oya1
1Department of Psychiatry, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan.
Background:
The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive.
Objective:
We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD.
Methods:
We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses.
Results:
Thirty studies (n = 7,567; memantine versus placebo: N = 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95% CIs) = -0.34, -0.15, p < 0.00001, I2 = 35% ] and BD (SMD = -0.16, 95% CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95% CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95% CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95% CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = -0.11, 95% CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95% CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups.
Conclusions:
The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.
Insights
This meta-analysis found memantine effective for Alzheimer's disease (AD), improving cognitive function and behavioral disturbances when used alone or with cholinesterase inhibitors (ChEIs). Results suggest memantine is a credible treatment option for AD patients.
Area of Science:
- Neuroscience
- Pharmacology
- Geriatrics
Background:
- The clinical effectiveness of memantine for Alzheimer's disease (AD) requires further clarification.
- Existing research presents inconclusive findings on memantine's benefits in AD patients.
Purpose of the Study:
- To conduct an updated systematic review and meta-analysis evaluating the efficacy and safety of memantine in Alzheimer's disease.
- To synthesize evidence from randomized controlled trials to determine memantine's impact on cognitive function and behavioral disturbances.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials involving memantine for AD.
- Primary outcome measures included cognitive function (CF) and behavioral disturbances (BD) scores, alongside all-cause discontinuation.
- Random-effects models were employed to calculate effect sizes.
Main Results:
- Memantine significantly improved cognitive function (SMD -0.24) and behavioral disturbances (SMD -0.16) compared to placebo.
- In moderate-to-severe AD patients, memantine demonstrated superior reduction in BD (SMD -0.20).
- Combination therapy (memantine + cholinesterase inhibitors) showed greater reduction in BD (SMD -0.20) and a trend for CF improvement compared to ChEIs alone.
Conclusions:
- Memantine demonstrates credible efficacy and safety as a monotherapy for Alzheimer's disease.
- Combining memantine with cholinesterase inhibitors offers additional benefits in managing behavioral disturbances and potentially cognitive function.
- The findings support the use of memantine, alone or in combination, for treating Alzheimer's disease.
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