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 non randomized 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% CI]: -9.1 [-11, -7.23], -7.2 [-8.85, -5.55], and -4.9 [-6.29, -3.51]. Adverse drug events (ADE) did not differ significantly between patients treated with memantine compared to placebo.

Conclusion. Memantine may be effective and well-tolerated as prophylaxis for episodic migraine.