{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:44:38Z","timestamp":1791229478364,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Health Administration\u2014Gerencia Regional de Salud (GRS), Castilla y Le\u00f3n, Salud Castilla y Leon (SACYL)","award":["GRS 2284\/A\/2020"],"award-info":[{"award-number":["GRS 2284\/A\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.<\/jats:p>","DOI":"10.3390\/life14070910","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T14:26:50Z","timestamp":1721744810000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acute and Preventive Treatment of COVID-19-Related Headache: A Series of 100 Patients"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-1064","authenticated-orcid":false,"given":"David","family":"Garc\u00eda-Azor\u00edn","sequence":"first","affiliation":[{"name":"Department of Medicine, Toxicology and Dermatology, Faculty of Medicine, University of Valladolid, 47002 Valladolid, Spain"},{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Garc\u00eda-Ruiz","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Sierra-Menc\u00eda","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-9798","authenticated-orcid":false,"given":"Y\u00e9sica","family":"Gonz\u00e1lez-Osorio","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Recio-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Gonz\u00e1lez-Celestino","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-5905","authenticated-orcid":false,"given":"Cristina","family":"Garc\u00eda-Iglesias","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-4197","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Planchuelo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Imaging Processing Laboratory, Escuela Superior de Telecomunicaciones (ETSI), Universidad de Valladolid, 47002 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-2911","authenticated-orcid":false,"given":"Ana Echavarr\u00eda","family":"\u00cd\u00f1iguez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitario de Burgos, 09006 Burgos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7493-6002","authenticated-orcid":false,"given":"\u00c1ngel L.","family":"Guerrero-Peral","sequence":"additional","affiliation":[{"name":"Department of Medicine, Toxicology and Dermatology, Faculty of Medicine, University of Valladolid, 47002 Valladolid, Spain"},{"name":"Headache Unit, Department of Neurology, Hospital Cl\u00ednico Universitario de Valladolid, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3820","DOI":"10.1111\/ene.15040","article-title":"Headache as an acute and post-COVID-19 symptom in COVID-19 survivors: A meta-analysis of the current literature","volume":"28","author":"Cuadrado","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14674","DOI":"10.1038\/s41598-021-94220-6","article-title":"Frequency and phenotype of headache in COVID-19: A study of 2194 patients","volume":"11","author":"Sierra","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s10194-020-01165-8","article-title":"Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: A retrospective cohort study","volume":"21","author":"Trigo","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/03331024211068074","article-title":"Post-COVID-19 persistent headache: A multicentric 9-months follow-up study of 905 patients","volume":"42","author":"Membrilla","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1177\/0333102420965146","article-title":"Phenotypic characterization of acute headache attributed to SARS-CoV-2: An ICHD-3 validation study on 106 hospitalized patients","volume":"40","author":"Guerrero","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_6","unstructured":"World Health Organization (2024, May 17). Clinical Services and Systems, Communicable Diseases, Technical Advisory Group on SARS-CoV-2 Virus Evolution. A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus, Available online: https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-Post_COVID-19_condition-Clinical_case_definition-2021.1."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s10194-021-01367-8","article-title":"Headache, anosmia, ageusia and other neurological symptoms in COVID-19: A cross-sectional study","volume":"23","author":"Albuquerque","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jocn.2021.04.001","article-title":"Post-COVID 19 neurological syndrome: Implications for sequelae\u2019s treatment","volume":"88","author":"Janjua","year":"2021","journal-title":"J. Clin. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1177\/0333102420965157","article-title":"Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution","volume":"40","author":"Caronna","year":"2020","journal-title":"Cephalalgia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1111\/head.13967","article-title":"Headache as a Cardinal Symptom of Coronavirus Disease 2019: A Cross-Sectional Study","volume":"60","author":"Membrilla","year":"2020","journal-title":"Headache"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s10194-020-01188-1","article-title":"Headache characteristics in COVID-19 pandemic-a survey study","volume":"21","author":"Uygun","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1111\/ene.14718","article-title":"Headache during SARS-CoV-2 infection as an early symptom associated with a more benign course of disease: A case-control study","volume":"28","author":"Fanjul","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/head.14197","article-title":"Toward a better understanding of persistent headache after mild COVID-19: Three migraine-like yet distinct scenarios","volume":"61","author":"Caronna","year":"2021","journal-title":"Headache"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1007\/s10072-021-05444-3","article-title":"New daily persistent headache after SARS-CoV-2 infection: A report of two cases","volume":"42","author":"Dono","year":"2021","journal-title":"Neurol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s10194-022-01450-8","article-title":"Long COVID headache","volume":"23","author":"Tana","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.ijsu.2014.07.013","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies","volume":"12","author":"Altman","year":"2014","journal-title":"Int. J. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1177\/0333102418758283","article-title":"Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults","volume":"38","author":"Tassorelli","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1177\/0333102419828967","article-title":"Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition","volume":"39","author":"Diener","year":"2019","journal-title":"Cephalalgia."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5702","DOI":"10.1007\/s00415-022-11225-5","article-title":"Amitriptyline for post-COVID-19 headache. Effectiveness, tolerability, and response predictors","volume":"269","author":"Arias","year":"2022","journal-title":"J. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s10194-022-01402-2","article-title":"The global prevalence of headache: An update, with analysis of the influences of methodological factors on prevalence estimates","volume":"23","author":"Stovner","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1177\/0333102410382794","article-title":"One-year prevalence of migraine in Spain: A nationwide population-based survey","volume":"31","author":"Mateos","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/head.13903","article-title":"COVID-19 and Headache Medicine: A Narrative Review of Non-Steroidal Anti-Inflammatory Drug (NSAID) and Corticosteroid Use","volume":"60","author":"Arca","year":"2020","journal-title":"Headache"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s40264-021-01089-5","article-title":"NSAIDs and COVID-19: A Systematic Review and Meta-analysis","volume":"44","author":"Moore","year":"2021","journal-title":"Drug Saf."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1111\/j.1468-1331.2010.03070.x","article-title":"EFNS guideline on the treatment of tension-type headache\u2014Report of an EFNS task force","volume":"17","author":"Bendtsen","year":"2010","journal-title":"Eur. J. Neurol."},{"key":"ref_26","first-page":"613","article-title":"Preventive Migraine Treatment","volume":"27","author":"Burch","year":"2021","journal-title":"Continuum"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Everitt, H., Baldwin, D.S., Stuart, B., Lipinska, G., Mayers, A., Malizia, A.L., Manson, C.C., and Wilson, S. (2018). Antidepressants for insomnia in adults. Cochrane Database Syst. Rev., CD010753.","DOI":"10.1002\/14651858.CD010753.pub2"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/fampra\/cmw134","article-title":"Amitriptyline for musculoskeletal complaints: A systematic review","volume":"34","author":"Bindels","year":"2017","journal-title":"Fam. Pract."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moore, R.A., Derry, S., Aldington, D., Cole, P., and Wiffen, P.J. (2015). Amitriptyline for neuropathic pain in adults. Cochrane Database Syst. Rev., CD008242.","DOI":"10.1002\/14651858.CD011603"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Guaiana, G., Barbui, C., and Hotopf, M. (2007). Amitriptyline for depression. Cochrane Database Syst. Rev., CD004186.","DOI":"10.1002\/14651858.CD004186.pub2"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1136\/jnnp-2016-313458","article-title":"Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention","volume":"87","author":"Ribeiro","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/j.clinthera.2009.03.020","article-title":"Topiramate versus amitriptyline in migraine prevention: A 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult migraineurs","volume":"31","author":"Dodick","year":"2009","journal-title":"Clin. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jackson, J.L., Cogbill, E., Santana-Davila, R., Eldredge, C., Collier, W., Gradall, A., Sehgal, N., and Kuester, J. (2015). A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130733"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10194-009-0171-x","article-title":"Post-infectious new daily persistent headache may respond to intravenous methylprednisolone","volume":"11","author":"Prakash","year":"2010","journal-title":"J. Headache Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"386","DOI":"10.55782\/ane-2021-041","article-title":"Greater occipital nerve block efficacy in COVID 19 associated headache: A preliminary study","volume":"81","author":"Sonkaya","year":"2021","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/23744235.2021.1924397","article-title":"Long COVID or post-COVID-19 syndrome: Putative pathophysiology, risk factors, and treatments","volume":"53","author":"Yong","year":"2021","journal-title":"Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/capr.12325","article-title":"Counselling and psychotherapy post-COVID-19","volume":"20","author":"Vostanis","year":"2020","journal-title":"Couns. Psychother. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1007\/s00415-021-10848-4","article-title":"Acute and post-acute neurological manifestations of COVID-19: Present findings, critical appraisal, and future directions","volume":"269","author":"Beghi","year":"2022","journal-title":"J. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"120162","DOI":"10.1016\/j.jns.2022.120162","article-title":"Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis","volume":"434","author":"Premraj","year":"2022","journal-title":"J. Neurol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1002\/alz.12644","article-title":"Changes in cognitive functioning after COVID-19: A systematic review and meta-analysis","volume":"18","author":"Crivelli","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Cacciatore, M., Raggi, A., Pilotto, A., Cristillo, V., Guastafierro, E., Toppo, C., Magnani, F.G., Sattin, D., Mariniello, A., and Silvaggi, F. (2022). Neurological and Mental Health Symptoms Associated with Post-COVID-19 Disability in a Sample of Patients Discharged from a COVID-19 Ward: A Secondary Analysis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19074242"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120591","DOI":"10.1016\/j.jns.2023.120591","article-title":"New-onset headache following COVID-19: An Italian multicentre case series","volume":"446","author":"Torrente","year":"2023","journal-title":"J. Neurol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Carri\u00f3n-Nessi, F.S., Ascanio, L.C., Pineda-Arap\u00e9, A.G., Oma\u00f1a-\u00c1vila, \u00d3.D., Mendoza-Mill\u00e1n, D.L., Romero, S.R., Almao-Rivero, A.B., Camejo-\u00c1vila, N.A., Gebran-Chedid, K.J., and Rodriguez-Saavedra, C.M. (2023). New daily persistent headache after SARS-CoV-2 infection in Latin America: A cross-sectional study. BMC Infect Dis., 23.","DOI":"10.1186\/s12879-023-08898-2"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1164\/rccm.201908-1581ST","article-title":"Diagnosis and treatment of adults with community-acquired pneumonia: An official clinical practice guideline of the American Thoracic Society and Infectious Disease Society of America","volume":"200","author":"Metlay","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_45","unstructured":"ARDS Definition Task Force, Ranieri, V.M., Rubenfeld, G.D., Taylor Thompson, B., Ferguson, N.D., Caldwell, E., Fan, E., Camporota, L., and Slutsky, A.S. (2012). Acute respiratory distress syndrome: The Berlin Definition. JAMA, 307, 2526\u20132533."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/7\/910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:48Z","timestamp":1760109648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/7\/910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,22]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["life14070910"],"URL":"https:\/\/doi.org\/10.3390\/life14070910","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1851702\/v1","asserted-by":"object"}]},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,22]]}}}