New AHS Emergency Department Migraine Guideline Elevates Prochlorperazine and Nerve Blocks, Advises Again Against Opioids

A new American Headache Society (AHS) evidence assessment updates recommendations for acute migraine treatment in emergency departments (EDs) for the first time since 2016, identifying 2 therapies that now carry a level A (“must offer”) designation: intravenous prochlorperazine and greater occipital nerve blocks (GONB). The guideline simultaneously designates hydromorphone IV as a level A “must not offer” treatment for migraine-related pain.¹

The update arises from systematic review of 26 randomized controlled trials published since the prior guideline published in 2016 and aims to standardize ED practice, reduce opioid use, and improve outcomes for the nearly one million ED patients with migraine seen annually, the guideline authors wrote.¹

The new recommendations stem from a collaborative systematic review led by investigators at Barrow Neurological Institute and the University of Calgary. “This update marks a major change in Emergency Department migraine care by introducing greater occipital nerve blocks and elevating intravenous prochlorperazine to level A (must offer) recommendations based on new high-quality evidence,” study co-author Jennifer Robblee, MD, a neurologist and headache specialist at Barrow Neurological Institute, said in a statement.²

Why an Update Was Needed

Migraine accounts for approximately one-fourth of the 3.5 million annual headache-related ED visits in the United States, but clinical outcomes remain suboptimal. Study authors cite research demonstrating that only 37.3% of patients report no headache at discharge. Variability in ED treatment persists despite the 2016 AHS guideline, they added. Opioid use has declined over time, from 54.1% (2007–2010) to 28.3% (2015–2018), yet opioids remain in circulation for headache-related care. The guideline authors note that ineffective or potentially harmful practices continue and that new high-quality evidence warranted a reassessment of parenteral therapies.¹

The update also incorporates treatment modalities not previously evaluated, including peripheral nerve blocks and the calcitonin gene-related peptide (CGRP) antagonist eptinezumab adminstered intravenously (IV), signs of the evolving scope of ED-based migraine management. The researchers posed 2 specific questions to guide their research for high-quality evidence¹:

• Which injectable medications should be considered effective for adults with migraine who visit an ED?
• Are nerve blocks, including sphenopalatine ganglion blocks, effective for the treatment of adults with migraine who visit an ED?

What the Evidence Shows

The systematic review identified 26 new randomized controlled trials evaluating 20 injectable treatments. These included 12 class I studies, 9 class II studies, and 4 class III studies. Based on this evidence, the guideline categorizes efficacy and issues updated recommendations:

The 8 therapies designated level U (no recommendation) are classified as such due to insufficient evidence, according to the guideline.

“Because nerve block use requires trained personnel and supplies, dissemination of procedural training and support for implementation will be essential,” study co-author Serena Orr, MD, neurologist, and associate professor at the University of Calgary’s Cumming School of Medicine, said in the statement. Orr and colleagues also point out that dissemination of the new recommendations poses challenges for some EDs, especially those that must modify order sets and shift entrenched prescribing habits.²

Implications for Emergency Practice

The guideline replaces the 2016 framework that rated IV prochlorperazine, IV metoclopramide, and SC sumatriptan as level B treatments (should offer). With new data, prochlorperazine becomes a level A cornerstone, and nerve blocks enter the guideline for the first time with the strongest possible recommendation. The update underscores the need to decrease reliance on opioids and adopt evidence-supported alternatives that improve the likelihood of pain relief at discharge.¹

The Focus for Future Research

The guideline authors note that future research should focus on large, well-designed ED-based randomized trials that follow International Headache Society recommendations while adapting endpoints to the ED context. Because parenteral therapies act quickly and many patients leave before two hours, they recommend a 1-hour primary outcome for pain relief and emphasize the need to validate “most bothersome symptom” measures in ED populations. They also encourage incorporating patient-centered outcomes—such as whether a patient would choose the same treatment again—and recording headache duration at presentation.¹

Key priorities include improving representation of racial and ethnic groups, studying newer agents like eptinezumab in ED-specific populations, and generating evidence for combination regimens. Implementation research, including treatment pathways and stepwise protocols, will be essential to move efficacy data into real-world ED practice.¹

Researchers emphasize that ED migraine care continues to fall short for many patients. By providing a more robust evidence base and clearer directive language, the updated recommendations aim to improve consistency of care, reduce treatment variability, and support faster, safer interventions.¹

References

1. Robblee J, Minen MT, Friedman BW, Cortel-LeBlanc MA, Cortel-LeBlanc A, Orr, SL. 2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies. Headache. 2025;00:1–24. doi: 10.1111/head.70016

2. Barrow Neurological Institute, University of Calgary study urges “major change” to migraine treatment in emergency departments. News release. Dignity Health. December 5, 2025. Accessed December 10, 2025. https://www.dignityhealth.org/arizona/about-us/press-center/press-releases/study-calls-for-major-change-in-ed-migraine-care