Second-line interventions for migraine in the emergency department: A narrative review

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

Research output: Contribution to journalArticlepeer-review


Objective: Millions of patients present to US emergency departments (ED) annually for the treatment of migraine. First-line treatments, including metoclopramide, prochlorperazine, and sumatriptan, fail to provide sufficient relief in up to one-third of treated patients. In this narrative review, we discuss the evidence supporting the use of injectable (intravenous, intramuscular, or subcutaneous) medications for patients in the ED who fail to improve sufficiently after treatment with first-line medication. Methods: We used the American Headache Society's guideline, “Management of Adults with Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies,” published in 2016, to identify first-line medications for migraine. We then conducted a PubMed search to determine whether any evidence supported the use of these medications as second-line therapy and whether any evidence existed to support the use of injectable therapies not discussed in the guideline as second-line therapy. Results: We identified only scant high-quality randomized data of second-line therapy. Therefore, we based our recommendations on medications that have reliably demonstrated efficacy as first-line treatment of migraine. These medications include injectable non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. Dihydroergotamine and valproic acid have some data supporting efficacy. More recently, greater occipital nerve blocks (GONBs) have been shown to be efficacious. With the exception of meperidine, opioids have been shown to be not efficacious. Most data published to date demonstrate no role for propofol and ketamine. Conclusions: There are no evidence-based second-line treatments of migraine in the ED setting. For patients with migraine, who fail to improve after treatment with a first-line medication, it is reasonable to use an intravenous NSAID or intravenous acetaminophen. Alternatively, clinicians adept at performing a GONB may offer this treatment.

Original languageEnglish (US)
Pages (from-to)1467-1474
Number of pages8
Issue number10
StatePublished - Nov 1 2021


  • emergency medicine
  • evidence-based treatment
  • migraine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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