Background Migraine is a common debilitating primary headache. Memantine is a non-competitive N-methyl D-aspartate (NMDA) antagonist that lowers neuronal excitability that could prevent migraine attacks.Objectives This study aimed to determine the efficacy and safety of memantine in patients experiencing episodic migraine attacks using a systematic review and meta-analysis.Methods We searched CENTRAL, MEDLINE, Scopus, Cochrane, LILACS, ClinicalTrials.gov, HERDIN and Google Scholar for relevant studies. Prespecified screening and eligibility criteria for inclusion were applied. Included studies underwent methodological quality assessment. Study design, patient characteristics, interventions given, and relevant outcomes were extracted and synthesized.Results This review included five relevant articles – 2 randomized controlled trials (RCT) and 3 observational studies (1 retrospective case-series, 2 prospective non-randomized open-label single arm trials). There were 109 patients included in the RCTs and 197 patients reported in the observational studies. Pooled data from the 2 RCTs showed that Memantine at 10mg/day decreased the monthly migraine days at 12 weeks compared to placebo with a mean difference of -1.58 [95% confidence interval (CI) -1.84, -1.32]. Observational studies also showed a decrease in migraine days per month with Memantine (5-20mg/day) after 12 weeks [95% CI]: -9.1 [-11, -7.23], -7.2 [-8.85, -5.55], and -4.9 [-6.29, -3.51]. There were no statistically significant adverse drug events (ADE) noted in patients treated with Memantine compared to placebo.Conclusion Memantine may be effective and well-tolerated as prophylaxis for episodic migraine.

Introduction. Migraine is a common, debilitating primary headache. Memantine is a non-competitive N-methyl D-aspartate (NMDA) antagonist that lowers neuronal excitability that could prevent migraine attacks. This study aimed to determine the efficacy and safety of memantine in patients with episodic migraine attacks using a systematic review and meta-analysis.Methods. We searched CENTRAL, MEDLINE, Scopus, Cochrane, LILACS, ClinicalTrials.gov, HERDIN and Google Scholar for relevant studies until July 31, 2020. Prespecified screening and eligibility criteria for inclusion were applied. Included studies underwent methodological quality assessment. Study design, patient characteristics, interventions given, and relevant outcomes were extracted and synthesized.Results. This review included five relevant articles -two randomized controlled trials (RCT) and three nonrandomized studies (one retrospective records review and survey, two prospective open-label single-arm trials). There were 109 patients included in the RCTs and 197 patients reported in the non-randomized studies. Pooled data from the two RCTs showed that memantine at 10 mg/day significantly decreased the monthly number of migraine days at 12 weeks compared to placebo with a mean difference of -1.58 [95% confidence interval (CI) -1.84, -1.32]. Non-randomized studies also showed a decrease in migraine days per month with memantine (5 to 20 mg/day) after 12 weeks [95%