Second-line Interventions for Migraine in the Emergency Department

A Narrative Review

Farnam Kazi MD; Mallika Manyapu MD; Maha Fakherddine MD; Kumelachew Mekuria MD; Benjamin W. Friedman MD, MS


Headache. 2021;61(10):1467-1474. 

In This Article


This is a narrative review based on the American Headache Society's Management of Adults with Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. We identified all medications reviewed in the AHS guideline and performed updated searches using the name of the medication and the search terms "(migraine or headache)" and "randomized." We performed this search using the National Library of Medicine's PubMed search engine ( The final search was conducted on June 5, 2021. In addition to the PubMed search, we reviewed the reference lists of all published studies identified in our search and consulted with experts knowledgeable on the intersection of headache and emergency medicine. Our goal was to identify high-quality literature that would inform this review. Specifically, we were searching for randomized studies of injectable (intravenous, intramuscular, or subcutaneous) medications conducted among patients with migraine. We included any study that attempted to discriminate between migraine and non-migraine headaches, or in which the vast majority (≥75%) of the participants had migraine. We hoped to identify studies of patients who were administered medication in the ED, failed to improve sufficiently, and then were randomized to active treatment or control. However, to enable a more robust discussion of the topic at hand, we also included studies that tested medications not just as second-line therapy but as first-line therapy as well. We included studies that utilized placebo or active control. Two authors reviewed every identified study and came to a consensus about whether or not the study met our inclusion criteria. Identified studies were then included in our narrative review.