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Original Investigation
June 15, 2021

Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Mayo Clinic Evidence-based Practice Center, Rochester, Minnesota
  • 2Department of Neurology, Mayo Clinic, Scottsdale, Arizona
  • 3Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
  • 4Department of Library–Public Services, Mayo Clinic, Rochester, Minnesota
  • 5Division of Health Care Delivery Research, Mayo Clinic, Rochester, Minnesota
JAMA. 2021;325(23):2357-2369. doi:10.1001/jama.2021.7939
Key Points

Question  What are the benefits and adverse events associated with acute treatments for episodic migraine in adults?

Findings  In this systematic review and meta-analysis that included 15 systematic reviews and 115 randomized clinical trials of 28 803 participants with migraine headache, multiple acute interventions, including nonsteroidal anti-inflammatory drugs, triptans, calcitonin gene-related peptide receptor antagonists, 5-HT1F receptor agonist, dihydroergotamine, acetaminophen, and remote electrical neuromodulation, were associated with improvements in short-term pain outcomes, with moderate to high strength of evidence. The evidence for these end points regarding opioids and other interventions was low or insufficient.

Meaning  For the acute treatment of migraine, several established and newer therapies were associated with improvements in short-term pain outcomes, with varying strengths of evidence.


Importance  Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.

Objective  To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.

Data Sources  Multiple databases from database inception to February 24, 2021.

Study Selection  Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.

Data Extraction and Synthesis  Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.

Main Outcomes and Measures  The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.

Findings  Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.

Conclusions and Relevance  There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.