{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:04:27Z","timestamp":1790805867139,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"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. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Prophylactic medication in clinical detoxification programs for the treatment of medication overuse headache is still debated. Gastrodin, a main bioactive constituent of <jats:italic>Rhizoma Gastrodiae<\/jats:italic>, has been applied clinically to treat primary headache for more than 30 years in China due to its potential analgesic and anti-migraine mechanisms. However, clinical evidence supporting its routing use in MOH is insufficient. The present study aims to investigate the efficacy and tolerability of oral gastrodin in medication overuse headache.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multicenter, randomized, double-blind, parallel, placebo-controlled trial will be performed. A target sample size of 186 patients who fulfill the International Classification of Headache Disorders 3rd version (ICHD-3) criteria for MOH will be recruited and screened during a baseline screening period of 28 days before being randomly assigned to either the gastrodin or placebo group at a ratio of 1:1. Enrolled patients will be assessed for each 4 weeks during the 12-weeks double-blind phase and followed up at week 24. The primary endpoint is mean change in monthly headache day frequency. Secondary endpoints will be the proportion of remitted MOH, change in headache pain intensity, headache impact test (HIT-6) score, 50% responder rate, treatment failure, monthly acute medication intake days, and Short Form 36-Item Health Survey (SF-36) score. Tolerability will be assessed by drop-out rates though safety monitoring during treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The findings of the present study may help to provide new evidence on gastrodin as a prophylaxis treatment with both efficacy and high tolerability for the treatment of MOH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trail registration<\/jats:title><jats:p>Chinese Clinical Trail Registry (ChiCTR2200063719), Protocol Version 1.1, May, 09, 2022.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.1095298","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T10:31:05Z","timestamp":1677061865000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and tolerability of oral gastrodin for medication overuse headache (EASTERN): Study protocol for a multicenter randomized double-blind placebo-controlled trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Fanyi","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn C.","family":"Buse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanxiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1468-2982.2003.00824.x","article-title":"The international classification of headache disorders: 2nd edition","volume":"24","year":"2004","journal-title":"Cephalalgia"},{"key":"B2","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1177\/0333102413485658","article-title":"The International Classification of Headache Disorders, 3rd edition (beta version)","volume":"33","year":"2013","journal-title":"Cephalalgia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1177\/0333102414520768","article-title":"Can we know the prevalence of MOH?","volume":"34","author":"Steiner","year":"2014","journal-title":"Cephalalgia."},{"key":"B4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1177\/0333102419876909","article-title":"Monitoring chronic headache and medication-overuse headache prevalence in Denmark","volume":"40","author":"Westergaard","year":"2020","journal-title":"Cephalalgia."},{"key":"B5","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/S1474-4422(17)30299-5","article-title":"Global, regional, and national burden of neurological disorders during 1990\u20132015: a systematic analysis for the Global Burden of Disease Study 2015","volume":"16","author":"GBD","year":"2017","journal-title":"Lancet Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1046\/j.1526-4610.2002.02133_1.x","article-title":"Debate: Analgesic overuse is a cause, not consequence, of chronic daily headache. 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