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


Search Strategy

A comprehensive literature search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020. A manual review of references from retrieved articles and reviews was also performed. The following search terms were used: migraine disorders, migraine, headache disorders, or headache and memantine. A description of the full search strategy is included in Online Appendix 1. This report adheres to the preferred reporting items for systematic reviews and meta-analyses guidelines for conducting a systematic review and all elements of the protocol were developed a priori. The review was not registered in the International Prospective Register of Systematic Reviews (PROSPERO).[21]

Study Selection

Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Studies were excluded if they were animal studies, case reports, only in abstract form, protocols without results, or were not written in English. Studies including other forms of headache were excluded if efficacy and safety of migraine were not independently assessed. An initial screen of title and abstract was conducted for initial inclusion. Full text of the remaining articles was then reviewed to determine final inclusion in the systematic review. Two authors (V.M.M. and P.L.M.) independently screened and reviewed articles; any disagreement was resolved by a third author (J.N.B.).

Data Extraction

Data were extracted using a standardized data extraction process for each study. Data collection included authors, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects.

Quality Assessment

To assess the quality of evidence of the selected studies, the Jadad and Methodological Index for Non-Randomized Studies (MINORS) assessments were used. The Jadad assessment is used to assess the quality of evidence for randomized control trials. The scoring system assesses the randomization, masking, and accountability of a clinical trial with a score ranging from 0 to 5, with a score ≥3 being considered high quality.[22] The MINORS assessment consists of an eight-item checklist used for noncomparative studies (score range 0–16), with four additional items for comparative studies (score range 0–24); a higher score indicates a higher-quality study.[23] Each author independently reviewed each study with the final score determined with all authors at a consensus meeting (Online Appendix 2).