{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:07Z","timestamp":1789448587868,"version":"build-2803163510"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032551","name":"Haleon","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032551","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      A range of pharmacologic options is available for acute migraine treatment, yet the efficacy and safety of commonly used over-the-counter (OTC) therapies relative to newer prescription agents remain unclear. Given the scarcity of direct head-to-head trials, this network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluated selected OTC therapies against newer oral agents, including CGRP antagonists and the 5-HT\n                      <jats:sub>1<\/jats:sub>\n                      F receptor agonist.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted in PubMed, Embase, and CENTRAL for RCTs of acute migraine therapies published between January 1990 and July 2025. Primary outcomes were 2-h (2\u202fh) pain relief and pain freedom; secondary outcomes included 2-h photophobia, phonophobia and nausea. Effect sizes were calculated as relative risks (RRs) with 95% confidence intervals (CIs). A frequentist NMA was conducted to estimate comparative efficacy and safety across the treatment network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>This NMA synthesized evidence from 25 RCTs, including 5 different interventions across 19 dose categories, involving a total of 22,100 participants with migraine. Compared with placebo, acetaminophen, aspirin, and caffeine (AAC) combination showed superior 2\u202fh pain relief (RR, 1.76; 95% CI, 1.61\u20131.94; p-score\u202f=\u202f0.96), followed by ibuprofen 400\u202fmg and 200\u202fmg. For 2\u202fh pain freedom, AAC, ibuprofen 400\u202fmg, and lasmiditan 200\u202fmg showed broadly comparable favorable effects versus placebo, with similar RRs and p-scores. AAC also produced the greatest reductions in photophobia and phonophobia at 2\u202fh (photophobia: RR, 1.99; 95% CI, 1.62\u20132.45; p-score\u202f=\u202f0.97; phonophobia: RR, 1.53; 95% CI, 1.28\u20131.84; p-score\u202f=\u202f0.89), while ibuprofen Liquigel 400\u202fmg provided additional meaningful benefit. For nausea, rimegepant 75\u202fmg demonstrated the strongest effect (RR, 1.15; 95% CI, 1.08\u20131.22; p-score\u202f=\u202f0.85), followed by ibuprofen Liquigel 400\u202fmg and AAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this NMA, OTC therapies showed meaningful efficacy and favorable safety for acute episodic migraine versus placebo, with ibuprofen and AAC demonstrating consistent benefits across 2\u202fh pain and secondary outcomes. These findings support their use as effective, accessible options alongside newer oral agents. Larger trials and patient-level analyses are needed to refine efficacy, optimize dosing, and personalize migraine management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261325571<\/jats:ext-link>\n                      , Identifier CRD420261325571.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1884713","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:28:04Z","timestamp":1789446484000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative efficacy of AAC and ibuprofen versus lasmiditan, ubrogepant, and rimegepant for the acute treatment of episodic migraine in adults: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Ashoke","family":"Mitra","sequence":"first","affiliation":[{"name":"Haleon","place":["Warren, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy","family":"Franks","sequence":"additional","affiliation":[{"name":"Haleon","place":["Amersfoort, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Petruschke","sequence":"additional","affiliation":[{"name":"Haleon","place":["Warren, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijeet","family":"Dhiman","sequence":"additional","affiliation":[{"name":"Knowledge Centre, WNS Global Services","place":["Gurugram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitu","family":"Bansal","sequence":"additional","affiliation":[{"name":"Knowledge Centre, WNS Global Services","place":["Gurugram, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1177\/0333102417738202","article-title":"The international classification of headache disorders, 3rd edition","volume":"38","year":"2018","journal-title":"Cephalalgia"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s40122-024-00690-7","article-title":"The global burden of migraine: a 30-year trend review and future projections by age, sex, country, and region","volume":"14","author":"Dong","year":"2025","journal-title":"Pain Ther"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1111\/head.14709","article-title":"Prevalence and burden of migraine in the United States: a systematic 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