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

Article type: Research Article

Authors: Kishi, Taro^{a; 1; *} | Matsunaga, Shinji^{a; 1} | Oya, Kazuto^a | Nomura, Ikuo^a | Ikuta, Toshikazu^b | Iwata, Nakao^a

Affiliations: [a] Department of Psychiatry, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan | [b] Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University MS, USA

Correspondence: [*] Correspondence to: Taro Kishi, MD, PhD, Department of Psychiatry, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. Tel.: +81 562 93 9250; Fax: +81 562 93 1831; E-mail: tarok@fujita-hu.ac.jp..

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Alzheimer’s disease, behavioral disturbances, cognitive function, memantine, meta-analysis, systematic review

DOI: 10.3233/JAD-170424

Journal: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 401-425, 2017