Role of Memantine in the Prophylactic Treatment of Episodic Migraine

A Systematic Review

Vinita M. Mistry PharmD; Paige L. Morizio PharmD, BCPS; Marc J. Pepin PharmD, BCPS, BCGP; William E. Bryan PharmD, BCPS; Jamie N. Brown PharmD, FCCP, BCPS, BCACP


Headache. 2021;61(8):1207-1213. 

In This Article


The current literature evaluates the short-term use of memantine, with efficacy and safety data beyond 6 months still not yet established. Larger randomized controlled trials with longer durations, and using an active comparator, are needed to further evaluate the efficacy and safety of memantine. Another limitation of the included studies is the relatively small sample sizes, potentially decreasing its external validity. However, each study did demonstrate statistically significant results with the primary endpoint, eliminating the concern that the studies were underpowered. In addition, with no active comparators in the included studies, it is challenging to apply this evidence to currently available prophylactic options that are more frequently prescribed. Finally, two studies used an open-label design and all studies used a per protocol assessment, increasing the potential for bias and an overestimation of the benefit with memantine.