Memantine for Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis

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 sco res (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.