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

Abstract

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.

Acute Treatment of Migraine

“…Available evidence suggests that occipital nerve blocks are not as effective as metoclopramide but may be helpful if metoclopramide is not effective. 62 Nerve blocks are generally safe and well tolerated, however, and may be an option for patients in whom other treatments are contraindicated. 62 Opioid use should be avoided in the emergency department as opioids have lower evidence for effectiveness, are associated with medication-overuse headache and decreased subsequent responsiveness to acute treatment, and may reinforce emergency department use in patients seeking opioids.…”

“…62 Nerve blocks are generally safe and well tolerated, however, and may be an option for patients in whom other treatments are contraindicated. 62 Opioid use should be avoided in the emergency department as opioids have lower evidence for effectiveness, are associated with medication-overuse headache and decreased subsequent responsiveness to acute treatment, and may reinforce emergency department use in patients seeking opioids. Opioid use for the acute treatment of migraine in the emergency department has decreased over time, but more than one-fourth of patients in the United States were still given opioids for migraine in the emergency department as recently as 2018.…”

“…These drugs are associated with a higher risk of adverse effects, including hypotension and prolonged QT interval, and should be considered third-line treatments. Available evidence suggests that occipital nerve blocks are not as effective as metoclopramide but may be helpful if metoclopramide is not effective 62 . Nerve blocks are generally safe and well tolerated, however, and may be an option for patients in whom other treatments are contraindicated 62 …”

“…Available evidence suggests that occipital nerve blocks are not as effective as metoclopramide but may be helpful if metoclopramide is not effective 62 . Nerve blocks are generally safe and well tolerated, however, and may be an option for patients in whom other treatments are contraindicated 62 …”

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis

“…2,14 Studies assessing agents such as greater occipital nerve blocks, antibodies targeting the calcitonin gene-related peptide pathway, or other emerging parenteral medications were excluded as additional research on their effectiveness and safety is required before these agents can be recommended as a first-line treatment option. 2,15,16 Studies that included multiple treatment arms were eligible for inclusion when at least two treatment arms consisted of an eligible parenteral agent listed previously. In addition to the study medications, studies were allowed to provide patients with adjunct therapies such as corticosteroids to prevent subsequent relapse, or treatments to reduce the pain associated with administering the study drugs, or reduce the risk for adverse events (e.g., antihistamines, antiemetics).…”