{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:42:47Z","timestamp":1785426167115,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002632","name":"Hallym University","doi-asserted-by":"publisher","award":["HURF-2025-16"],"award-info":[{"award-number":["HURF-2025-16"]}],"id":[{"id":"10.13039\/501100002632","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HURF-2025-16"],"award-info":[{"award-number":["HURF-2025-16"]}],"id":[{"id":"https:\/\/ror.org\/03sbhge02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objective: Medication overuse headache (MOH) is a disabling secondary headache disorder that arises from an underlying primary headache, most commonly migraine. Although treatment reduces headache frequency and medication overuse, the interictal burden\u2014the impact experienced between headache attacks\u2014remains poorly characterized over the long term. This study evaluated interictal burden and clinical outcomes two years after MOH diagnosis. Methods: This study was derived from a prospective multicenter cohort of patients with MOH, using data from a single center. Of 149 patients enrolled between April 2020 and November 2022, 117 (78.5%) completed the two-year follow-up. Clinical characteristics, medication overuse, monthly headache days, and standardized questionnaires were assessed at baseline and follow-up. Interictal burden was evaluated at two years using the Migraine Interictal Burden Scale (MIBS-4), with scores \u22655 indicating severe burden. Results: At baseline, patients (81.2% female; median age, 45.0 years) reported a median of 16.0 monthly medication days (interquartile range, 13.0\u201323.0). Medication overuse decreased from 100% at baseline to 24.2% at one year and 17.1% at two years. Among 117 patients with available two-year MIBS-4 data, 25 (21.4%) had severe interictal burden. Compared with those without severe burden, these patients had greater headache-related impact and disability (HIT-6: 68.0 vs. 64.0, p = 0.019; MIDAS: 110.0 vs. 36.0, p = 0.002), higher psychological burden (PHQ-9: 11.0 vs. 8.0, p = 0.032; GAD-7: 7.0 vs. 4.0, p = 0.010), and were more likely to be current smokers (20.0% vs. 4.3%, p = 0.036). Notably, 14.4% of patients with resolved medication overuse still reported severe interictal burden. Conclusions: Two years after MOH diagnosis, severe interictal burden was observed in a substantial proportion of patients and was associated with greater baseline disability and psychological distress. These findings highlight the need for long-term monitoring and management beyond initial medication withdrawal.<\/jats:p>","DOI":"10.3390\/jcm15124785","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:04:04Z","timestamp":1781874244000},"page":"4785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Two-Year Outcomes and Interictal Burden After Treatment for Medication Overuse Headache"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-2831","authenticated-orcid":false,"given":"Yooha","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7, Keunjaebong-gil, Hwaseong 18450, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-3984","authenticated-orcid":false,"given":"Mi-Kyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7, Keunjaebong-gil, Hwaseong 18450, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4053-3763","authenticated-orcid":false,"given":"Soo-Jin","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Dongtan Sacred Heart Hospital, Hallym University College of Medicine, 7, Keunjaebong-gil, Hwaseong 18450, Gyeonggi-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1468-2982.2007.01288.x","article-title":"The global burden of headache: A documentation of headache prevalence and disability worldwide","volume":"27","author":"Stovner","year":"2007","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s10194-024-01755-w","article-title":"Medication-overuse headache: A narrative review","volume":"25","author":"Gosalia","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3344\/kjp.2022.35.1.4","article-title":"The evolving classifications and epidemiological challenges surrounding chronic migraine and medication overuse headache: A review","volume":"35","author":"Schembri","year":"2022","journal-title":"Korean J. Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.17340\/jkna.2023.1.1","article-title":"Medication-overuse headache: Diagnostic criteria, epidemiology, and treatment","volume":"41","author":"Park","year":"2023","journal-title":"J. Korean Neurol. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1177\/0333102411398400","article-title":"Quality of life impairment, disability and economic burden associated with chronic daily headache, focusing on chronic migraine with or without medication overuse: A systematic review","volume":"31","author":"Duru","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"A51","DOI":"10.1186\/1129-2377-16-S1-A51","article-title":"The association between temperament, depression, hopelessness and quality of life in medication-overuse headache patients","volume":"16","author":"Migliorati","year":"2015","journal-title":"J. Headache Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1007\/s10072-020-04716-8","article-title":"Economic burden of medication-overuse headache in Iran: Direct and indirect costs","volume":"42","author":"Togha","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_8","first-page":"A89","article-title":"Development and validation of the Migraine Interictal Burden Scale (MIBS): A self-administered instrument for measuring the burden of migraine between attacks","volume":"68","author":"Buse","year":"2007","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/head.14460","article-title":"Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study","volume":"63","author":"Lipton","year":"2023","journal-title":"Headache"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1177\/03331024211057184","article-title":"Interim analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE): A multicenter, comprehensive medication overuse headache registry","volume":"42","author":"Park","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Headache Classification Committee of the International Headache Society (IHS) (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia, 38, 1\u2013211.","DOI":"10.1177\/0333102417738202"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/0333102410379890","article-title":"Validation of the Headache Impact Test (HIT-6) across episodic and chronic migraine","volume":"31","author":"Yang","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1212\/WNL.56.suppl_1.S20","article-title":"Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability","volume":"56","author":"Stewart","year":"2001","journal-title":"Neurology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3928\/0048-5713-20020901-06","article-title":"The PHQ-9: A new depression diagnostic and severity measure","volume":"32","author":"Kroenke","year":"2002","journal-title":"Psychiatr. Ann."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","article-title":"A brief measure for assessing generalized anxiety disorder: The GAD-7","volume":"166","author":"Spitzer","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0025-6196(11)60561-2","article-title":"Assessing and managing all aspects of migraine: Migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life","volume":"84","author":"Buse","year":"2009","journal-title":"Mayo Clin. Proc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1186\/s10194-024-01927-8","article-title":"Interictal burden in migraine patients at the outset of CGRP monoclonal antibody prevention","volume":"25","author":"Lampl","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10194-022-01467-z","article-title":"Measuring interictal burden among people affected by migraine: A descriptive survey study","volume":"23","author":"Hubig","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1093\/pm\/pny028","article-title":"Factors related to migraine patients\u2019 decisions to initiate behavioral migraine treatment following a headache specialist\u2019s recommendation: A prospective observational study","volume":"19","author":"Minen","year":"2018","journal-title":"Pain Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s10194-026-02284-4","article-title":"Interictal burden, not ictal burden, drives work productivity impairment in headache disorders: Insights from a Japanese cross-sectional study","volume":"27","author":"Katsuki","year":"2026","journal-title":"J. Headache Pain"},{"key":"ref_21","first-page":"e98195","article-title":"Identifying hidden disability in migraine patients using the Migraine Interictal Burden Scale-4","volume":"17","author":"Hashimoto","year":"2025","journal-title":"Cureus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s10072-026-09029-w","article-title":"Translation and validation of the Migraine Interictal Burden Scale (MIBS-4) in an Italian clinical cohort","volume":"47","author":"Piella","year":"2026","journal-title":"Neurol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e3547","DOI":"10.1002\/brb3.3547","article-title":"Underrecognition of migraine-related stigmatizing attitudes and social burden: Results of the OVERCOME Japan study","volume":"14","author":"Igarashi","year":"2024","journal-title":"Brain Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s11916-024-01312-9","article-title":"Anxiety disorders, anxious symptomology and related behaviors associated with migraine: A narrative review of prevalence and impact","volume":"29","author":"Macko","year":"2025","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"571","DOI":"10.3988\/jcn.2022.18.5.571","article-title":"Prevalence rates of primary headache disorders and evaluation and treatment patterns among Korean neurologists","volume":"18","author":"Kim","year":"2022","journal-title":"J. Clin. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1001\/jamaneurol.2020.1179","article-title":"Comparison of 3 treatment strategies for medication overuse headache: A randomized clinical trial","volume":"77","author":"Carlsen","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1111\/pme.12517","article-title":"Pilot study of amitriptyline in the prophylactic treatment of medication-overuse headache: A 1-year follow-up","volume":"15","author":"Fan","year":"2014","journal-title":"Pain Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1212\/01.WNL.0000063322.14078.90","article-title":"Rates and predictors for relapse in medication overuse headache: A 1-year prospective study","volume":"60","author":"Katsarava","year":"2003","journal-title":"Neurology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1600-0404.2011.01542.x","article-title":"A randomized controlled trial on medication-overuse headache: Outcome after 1 and 4 years","volume":"191","author":"Hagen","year":"2011","journal-title":"Acta Neurol. Scand. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3988\/jcn.2023.0485","article-title":"Treatment Patterns and Persistence Among Patients Newly Diagnosed With Migraine in South Korea: A Retrospective Analysis of Health Claims Data","volume":"20","author":"Kim","year":"2024","journal-title":"J. Clin. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16013","DOI":"10.1038\/s41598-024-66906-0","article-title":"Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments","volume":"14","author":"Oh","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s10194-016-0696-8","article-title":"Risk of medication overuse headache across classes of treatments for acute migraine","volume":"17","author":"Thorlund","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1129-2377-14-10","article-title":"Advice alone versus structured detoxification programmes for complicated medication overuse headache (MOH): A prospective, randomized, open-label trial","volume":"14","author":"Rossi","year":"2013","journal-title":"J. Headache Pain"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kebede, Y.T., Mohammed, B.D., Tamene, B.A., Abebe, A.T., and Dhugasa, R.W. (2023). Medication overuse headache: A review of current evidence and management strategies. Front. Pain Res., 4.","DOI":"10.3389\/fpain.2023.1194134"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s10194-018-0875-x","article-title":"Medication-overuse headache: A widely recognized entity amidst ongoing debate","volume":"19","author":"Vandenbussche","year":"2018","journal-title":"J. Headache Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s10194-024-01813-3","article-title":"Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache\u2014A retrospective real-world analysis","volume":"25","author":"Scheffler","year":"2024","journal-title":"J. Headache Pain"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vincent, M., Viktrup, L., Nicholson, R.A., Ossipov, M.H., and Vargas, B.B. (2022). The not so hidden impact of interictal burden in migraine: A narrative review. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1032103"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/head.14819","article-title":"Predictors of migraine interictal burden: The hidden role of subjective memory complaints","volume":"65","author":"Sotero","year":"2025","journal-title":"Headache"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"130","DOI":"10.62087\/hpr.2024.0031","article-title":"Premonitory symptoms in migraine: Implications for disease burden and cognitive impairment, with some promising answers","volume":"26","year":"2025","journal-title":"Headache Pain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S1474-4422(19)30146-2","article-title":"Pathophysiology, prevention, and treatment of medication overuse headache","volume":"18","author":"Diener","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1526-4637.2011.01183.x","article-title":"Pain processing in medication overuse headache: A functional magnetic resonance imaging (fMRI) study","volume":"13","author":"Ferraro","year":"2012","journal-title":"Pain Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrneurol.2016.93","article-title":"Chronic migraine: Risk factors, mechanisms and treatment","volume":"12","author":"May","year":"2016","journal-title":"Nat. Rev. Neurol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4785\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:00:32Z","timestamp":1782450032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/12\/4785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":42,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcm15124785"],"URL":"https:\/\/doi.org\/10.3390\/jcm15124785","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]}}}