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The original search strategy was repeated and expanded to include studies of nerve blocks and sphenopalatine ganglion (SPG) blocks. We searched Medline, Embase, Cochrane, clinicaltrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform through February 10, 2025. Eligible studies were randomized controlled trials (RCTs) involving adults diagnosed with migraine, treated in the ED with intravenous (IV), intramuscular (IM), subcutaneous (SC), or nerve block (including SPG block) interventions. Two reviewers independently screened titles\/abstracts and full texts; a third reviewer resolved disagreements. Data were extracted using a standardized form and verified by a second reviewer. Risk of bias was assessed using the American Academy of Neurology (AAN) criteria. Where applicable, meta\u2010analyses were performed. Efficacy was categorized as highly likely, likely, or possibly effective or ineffective. Clinical recommendations were developed using the AAN guideline development process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The search identified 26 new RCTs evaluating 20 injectable treatments. Of these, 12 were rated class I (low risk of bias), 9 class II, and 4 class III. Prochlorperazine IV, dexketoprofen IV, sumatriptan SC, and greater occipital nerve blocks (GONB) were considered highly likely to be effective based on multiple class I studies. Chlorpromazine IV, metoclopramide IV, eptinezumab IV, ketorolac IV, and supraorbital nerve blocks (SONB) were considered likely effective based on one class I or multiple class II studies. Hydromorphone IV, propofol IV, and paracetamol IV were considered likely ineffective based on class I or multiple class II studies. After review of the evidence and a consensus process, recommendations were made for each intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Prochlorperazine IV and GONB must be offered to eligible adults presenting to the ED with a migraine attack for treatment of headache requiring parenteral therapy (level A \u2013 must offer) in those without contraindications, while hydromorphone IV must not be offered (level A \u2013 must not offer). Treatments that should be offered when appropriate (level B \u2013 should offer) include dexketoprofen IV, ketorolac IV, metoclopramide IV, sumatriptan SC, and SONB. Chlorpromazine IV, dexamethasone IV, and valproate IV may be offered (level C \u2013 may offer). Paracetamol IV may not be offered (level C \u2013 should not offer). Eptinezumab should be offered (level B) only for patients matching the clinical trial population but is rated level U \u2013 no recommendation for an ED\u2010specific population. Additional evidence is needed for caffeine, granisetron, ibuprofen, ketamine, lidocaine, normal saline, propofol, and SPG blocks, all currently rated level U \u2013 no recommendation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70016","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:52:48Z","timestamp":1764582768000},"page":"53-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["2025 guideline update to acute treatment of migraine for adults in the emergency department: The American Headache Society evidence assessment of parenteral pharmacotherapies"],"prefix":"10.1111","volume":"66","author":[{"given":"Jennifer","family":"Robblee","sequence":"first","affiliation":[{"name":"Department of Neurology, Lewis Headache Clinic Barrow Neurological Institute, Dignity Health  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia 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 Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achelle","family":"Cortel\u2010LeBlanc","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"},{"name":"Institut du Savoir Montfort  Ottawa Ontario Canada"},{"name":"360 Concussion Care  Ottawa Ontario Canada"},{"name":"Division of Neurology Queensway Carleton Hospital  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena L.","family":"Orr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Community Health Sciences, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Department of Clinical Neurosciences, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Division of Neurology Alberta Children's Hospital  Calgary 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