{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:24:34Z","timestamp":1787027074862,"version":"build-2736575974"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:00:00Z","timestamp":1662422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:p>The standard of care paradigm for migraine treatment has been based almost exclusively on approaches that grew out of the happenstance use of market pharmaceuticals. Only methysergide, which has long since been removed from use for safety concerns, the ergotamine family of drugs, and the triptans were explicitly developed with migraine and other vascular headaches in mind. While the forward and innovative thinking to utilize the broad array of agents to treat migraine served millions well, their therapeutic efficacy was often low, and adverse event profiles were troublesome in the least. Advances in biochemical and molecular biology and the application of advanced \u201cdesigning drugs\u201d methods have brought about a potentially significant shift in treatment. The gepants have efficacies similar to the triptans but without vascular safety or medication overuse concerns. Preventative gepants offer innovative approaches to prevention and efficacy that exceed even the CGRP monoclonal antibodies. Those monoclonal antibodies brought rapid and highly effective outcomes across the spectrum of migraine. They outpaced older oral medication efficacy and eliminated most adverse events while potentially improving compliance with monthly or quarterly dosing. Other serotonin receptors beyond the 5HT1B and1D receptors have been targeted for decades. They now lead us to better formulations of dihydroergotamine for efficacy, convenience, and tolerability, and a 5HT1F-specific acute treatment like the gepants opens new options for acute management. Neuromodulation goes back to the mid-1800's. Our improved understanding of applied biomedical engineering has brought forward several tantalizing devices, including the application of currents distant from the target and patient regulated. Whether these advances change the paradigm of migraine treatment and standards of care remains to be seen, and issues such as cost and patient acceptance will help mold it.<\/jats:p>","DOI":"10.3389\/fpain.2022.873179","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T00:27:23Z","timestamp":1662424043000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["New Approaches to Shifting the Migraine Treatment Paradigm"],"prefix":"10.3389","volume":"3","author":[{"given":"Brian","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick G.","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jns.2016.11.071","article-title":"Migraine affects 1 in 10 people worldwide featuring recent rise: a systematic review and meta-analysis of community-based studies involving 6 million participants","volume":"372","author":"Woldeamanuel","year":"2017","journal-title":"J Neurol Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1111\/head.13281","article-title":"The prevalence and impact of migraine and severe headache in the united states: figures and trends from Government Health Studies","volume":"58","author":"Burch","year":"2018","journal-title":"Headache."},{"key":"B3","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s10194-015-0544-2","article-title":"Headache disorders are third cause of disability worldwide","volume":"16","author":"Steiner","year":"2015","journal-title":"J Headache Pain."},{"key":"B4","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1212\/01.wnl.0000323925.29520.e7","article-title":"Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment","volume":"71","author":"Bigal","year":"2008","journal-title":"Neurology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1111\/head.13543","article-title":"Episodic and chronic migraine in primary care","volume":"59","author":"Young","year":"2019","journal-title":"Headache."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1212\/WNL.0b013e3182535d20","article-title":"Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society","volume":"78","author":"Silberstein","year":"2012","journal-title":"Neurology."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1212\/WNL.0b013e3182535d0c","article-title":"Quality standards subcommittee of the American Academy of Neurology and the American Headache Society. 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