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Practice Guideline
. 2025 Oct;45(10):3331024251388377.
doi: 10.1177/03331024251388377. Epub 2025 Oct 21.

International Headache society evidence-based guidelines on the use of non-invasive neuromodulation devices for the acute and preventive treatment of migraine

Hsiangkuo Yuan  1 , Serena L Orr  2   3   4 , Mohammad A M Al-Karagholi  5 , Messoud Ashina  5 , Fred Cohen  6   7 , Hans-Christoph Diener  8   9 , David W Dodick  10 , Rigmor Højland Jensen  5 , Michael J Marmura  1 , Daniele Martinelli  11   12 , Manjit S Matharu  13 , Anja S Petersen  5 , Patricia Pozo-Rosich  14   15 , Simona Sacco  16 , Lucy Simmonds  13 , Cristina Tassorelli  12   17 , Stewart J Tepper  18   19 , Gisela M Terwindt  20 , Shuu-Jiun Wang  21   22 , Jiunn-Tyng Yeh  23   24 , Stephen D Silberstein  1
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Free article
Practice Guideline

International Headache society evidence-based guidelines on the use of non-invasive neuromodulation devices for the acute and preventive treatment of migraine

Hsiangkuo Yuan et al. Cephalalgia. 2025 Oct.
Free article

Abstract

ObjectiveTo develop evidence-based clinical practice guidelines for non-invasive neuromodulation devices in acute and preventive migraine treatment.MethodsA systematic review was conducted across six databases from 1946 to April 2025. Randomized controlled trials evaluating Food and Drug Administration-cleared or Conformité Européenne (CE)-marked non-invasive neuromodulation devices were included. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, and recommendations were developed through consensus following GRADE Evidence-to-Decision frameworks. The working group comprised 15 senior members and six junior members.ResultsFrom 1536 initial records, 15 studies met the inclusion criteria and were finally used to develop evidence-based recommendations. Evidence quality ranged from very low to moderate. Weak recommendations were issued for SAVI Dual, Cefaly, Relivion, and Nerivio in the treatment of acute migraine attacks, and for gammaCore Sapphire, Cefaly, and Nerivio in the preventive migraine treatment. Other cleared devices received no recommendations or have no eligible studies for the GRADE assessment. The primary limitations across studies included imprecision due to small sample sizes and various methodological concerns. Additionally, expert consensus recommendations were developed for devices and clinical scenarios not adequately covered by randomized controlled trials, including potential applications in pediatric populations, vestibular migraine, chronic migraine, menstrual migraine, and medication overuse headache.ConclusionNon-invasive neuromodulation devices offer promising alternatives to drug treatment for migraine management. These devices are safe and generally well tolerated and devoid of drug interactions. While current evidence quality varies, ongoing research and technological advancements show encouraging potential. Future studies should adhere to International Headache Society guidelines for neuromodulation device trials, address proper sham controls and blinding assessment, and account for patient adherence challenges in device use. Expanded insurance coverage would enhance cost-effectiveness and device accessibility. These guidelines provide a framework for clinical decision-making while highlighting areas requiring further research.

Keywords: electric stimulation; migraine disorders; neuromodulation; practice guideline; transcranial magnetic stimulation; vagus nerve stimulation.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HY, in the past 24 months, received funding from the AHS Early-Stage Investigator Research Award; institutional support for serving as an investigator from Teva, AbbVie, Ipsen, Pfizer, Parema, Shiratronics, Johnson & Johnson; consultant/advisory fees from Salvia, AbbVie, Pfizer, Cerenovus; and royalties from Cambridge University Press and MedLink Neurology.SLO receives royalties from Cambridge University Press. She serves on the editorial boards of Headache, Neurology, and the American Migraine Foundation. She also has research funding from the Canadian Institutes of Health Research, the Alberta Children's Hospital Research Institute, and the American Headache Society.MMA-K declares no competing interests.MA is a consultant, speaker, or scientific advisor for AbbVie, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Pfizer, and Teva; a primary investigator for ongoing Lundbeck and Pfizer trials; and is the past president of the International Headache Society. MA is supported through the Lundbeck Foundation Professor Grant (R310-2018-3711), Novo Nordisk Foundation Grant (Grant ID: 0101709), the Danish National Research Foundation Grant (DNRF188) and serves as associate editor of the Journal of Headache and Pain and associate editor of Brain.FC received honoraria for consulting/speaking/writing from Teva, Pfizer, AbbVie, Eli Lilly, Springer Nature, and Medlink Neurology.HCD received honoraria for oral presentations from: Betapharm, Lundbeck, Orion, and WebMD. The German Research Council (DFG) supports headache research by HCD. HCD serves on the editorial boards of Cephalalgia, Lancet Neurology, and Drugs.DWD received consulting fees from Amgen, Atria, CapiThera Ltd, Cerecin, Ceruvia Lifesciences LLC, CoolTech, Ctrl M, Allergan, AbbVie, Biohaven, GlaxoSmithKline, Lundbeck, Eli Lilly, Novartis, Impel, Satsuma, Theranica, WL Gore, Genentech, Nocira, Perfood, Praxis, AYYA Biosciences, Revance, and Pfizer; received honoraria from American Academy of Neurology, Headache Cooperative of the Pacific, Canadian Headache Society, MF Med Ed Research, BioPharm Communications, CEA Group Holding Company (Clinical Education Alliance LLC), Teva (speaking), Amgen (speaking), Eli Lilly (speaking), Lundbeck (speaking), Pfizer (speaking), Vector Psychometric Group, Clinical Care Solutions, CME Outfitters, Curry Rockefeller Group, DeepBench, Global Access Meetings, KLJ Associates, Academy for Continued Healthcare Learning, Majallin LLC, MedLogix Communications, Medica Communications LLC, MJH Life Sciences, Miller Medical Communications, WebMD Health/ Medscape, Wolters Kluwer, Oxford University Press, and Cambridge University Press. Non-profit board membership: American Brain Foundation, American Migraine Foundation, ONE Neurology, Precon Health Foundation, International Headache Society Global Patient Advocacy Coalition, Atria Health Collaborative, Arizona Brain Injury Alliance, and Domestic Violence HOPE Foundation/Panfila; received research support from Department of Defense, National Institutes of Health, Sperling Foundation, American Migraine Foundation, Henry Jackson Foundation, and Patient-Centered Outcomes Research Institute (PCORI). Stock options/shareholder/ patents/board of directors: Ctrl M (options), Aural Analytics (options), Axon Therapeutics, ExSano (options), Palion (options), Man and Science, Healint (options), Theranica (options), Second Opinion/ Mobile Health (options), Epien (options/board), Nocira (options), Matterhorn (shares/board), Ontologics (shares/board), King-Devick Technologies (options/board), Precon Health (options/board), AYYA Biosciences (options), Axon Therapeutics (options/board), Cephalgia Group (options/board), and Atria Health (options/employee). Patent 17189376.1-1466:v, Title: Onabotulinum Toxin Dosage Regimen for Chronic Migraine Prophylaxis (Non-royalty bearing). Patent application submitted: SynaQuell (PreCon Health).RHJ is the principal investigator in clinical trials, and has given lectures to TEVA, Lundbeck Pharma, AbbVie, Pfizer, and Eli Lilly. Director of Danish Headache center, Director in Lifting The Global Burden (unpaid), Chair of Master of Headache Disorders at University of Copenhagen (personal payment). Her institution received a restricted research grant from Lundbeck Pharma and Novo Nordisk FoundationMJM, within the past 24 months, has received compensation for consultation from Lundbeck. He has received institutional support for serving as principal investigator from Teva, Pfizer and AbbVie.DM declares honoraria from Lundbeck; honoraria for participation in an advisory board from AbbVie.MSM is chair of the medical advisory board of the CSF Leak Association; has served on advisory boards for AbbVie, Eli Lilly, Lundbeck, Pfizer, Salvia, and TEVA; has received payment for educational presentations from AbbVie, Eli Lilly, Lundbeck, Organon, Pfizer, and TEVA; has received grants from Abbott, Medtronic, and Ehlers Danlos Society; and has a patent on system and method for diagnosing and treating headaches (WO2018051103A1, issued).ASP received personal payment for lectures on headache for general practitioners from Pfizer, she has participated in a two-day neurological symposium sponsored by Lundbeck Pharma, and her institution got a restricted research grant from Lundbeck pharma.PPR has received, in the last three years, honoraria as a consultant and speaker for: AbbVie, Almirall, Dr Reddy's, Eli Lilly, Lundbeck, Medscape, Novartis, Organon, Pfizer and Teva. Her research group has received research grants from AbbVie, Novartis and Teva; as well as, Instituto Salud Carlos III, EraNet Neuron, European Regional Development Fund (001-P-001682) under the framework of the FEDER Operative Programme for Catalunya 2014-2020 - RIS3CAT; has received funding for clinical trials from AbbVie, Amgen, Biohaven, Eli Lilly, Novartis, Pfizer, Teva. She is the Honorary Secretary of the International Headache Society. She is an associate editor for Cephalalgia and Neurologia. She is the founder of www.midolordecabeza.org. PPR does not own stocks from any pharmaceutical company.SS received personal fees as speaker or advisor: Abbvie, Bayer, Boheringer, Eli Lilly, Lundbeck, Pfizer, Teva. Intellectual: president European Stroke Organisation, editor-in-chief Cephalalgia and Cephalalgia Reports, assistant editor for Stroke.LS received funding from The Wellington Hospital, LondonCT received personal fees for participating in advisory boards or for lecturing at sponsored symposia for AbbVie, Dompé, Eli Lilly, Ipsen, Lundbeck, Medscape, Pfizer and Teva. She is principal investigator or collaborator in clinical trials sponsored by AbbVie, Eli Lilly, Ipsen, Lundbeck, Pfizer and Teva. She has received research grants from the European Commission, the Italian Ministry of Health, the Italian Ministry of University, the Migraine Research Foundation and the Italian Multiple Sclerosis Foundation.SJT received research funding: Abbvie, Aeon, Amgen, Annovis, Axsome, Biohaven, Cassava, Cognition, Eli Lilly, Inhibikase, Ipsen, Lundbeck, Merz, Neurolief, Pfizer, PrecisionMed, Revance, Scilex, Suven, UCB; consultant and/or Advisory Boards (honoraria): Abbvie, Aeon, Alphasights, Amgen, Aruene/eNeura, Atheneum, Axsome Therapeutics, Bausch Health, Becker Pharmaceutical Consulting, Catch Therapeutics, ClearView Healthcare Partners, ClickTherapeutics, CoolTech, CRG, Decision Resources, Defined Health, DRG, DocDelta, Dr Reddy's, Eli Lilly, ExpertConnect, FCB Health, Fenix, Gilmartin Capital, GLG, Guidepoint Global, Health Advances, Health Science Communications, HMP Communications, Impel, Initiator Pharma, InteractiveForums, IQVIA, Keyquest, Ki Health Partners, Krog and Partners, Lundbeck, M3 Global Research, Magellan Health, Magnolia Innovation, Miravo Healthcare, MJH Holdings, Neurofront Therapeutics, Neurolief, Nocira, Novartis, P Value Communications, Pain Insights, Inc, Palion Medical, Perfood, Pfizer, Pulmatrix, Putnam Associates, Rehaler, SAI MedPartners, Satsuma, Scilex, Slingshot Insights, Spherix Global Insights, Strategy Inc, Synapse Medical Communication, System Analytic, Taylor and Francis, Tegus, Teva, Theranica, Third Bridge, Tonix, Trinity Partners, Unity HA, Vial, XOC; speakers Bureau: AbbVie, Dr Reddy's, Eli Lilly, Lundbeck, Pfizer, Scilex, Teva, Tonix; CME honoraria: American Academy of Neurology, American Headache Society, Annenberg Center for Health Sciences, Catamount Medical Education, Consortium for Research Education Social Awareness and Training In Neurosciences, Diamond Education Foundation, Forefront Collaborative, Haymarket Medical Education, HMP Global, Medical Education Speakers Network, Medical Learning Institute Peerview, Migraine Association of Ireland, Miller Medical Education, National Association for Continuing Education, North American Center for CME, The Ohio State University, Physicians’ Education Resource, PlatformQ Education, Primed, Vindico Medical Education, WebMD/MedscapeGMT reports consultancy or industry support from Novartis, Lilly and Teva, Allergan/Abbvie, Lundbeck, Pfizer and Interactive Studios, as well as independent support from the European Community, Dutch Heart Foundation, Dutch Research Council, Dutch Brain Foundation and Dioraphte.SJW has served on the advisory boards of Taiwan Pfizer, AbbVie and Hava-Biopharma; has received honoraria as a moderator from AbbVie, Pfizer and Biogen; and has been the principal investigator in clinical trials sponsored by AbbVie, Novartis, Lundbeck and Pfizer. He has received research grants from the National Council of Technology and Science of Taiwan, Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, Taipei Veterans General Hospital, and Taiwan branches of Eli Lilly and Novartis.JTY declared no conflict of interest.SDS provides consultation to Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Curelator Inc., Depomed, Dr Reddy's Laboratories, Ensured Inc., electroCore Medical LLC, eNeura Therapeutics, Insys Therapeutics, Lilly USA LLC, Supernus Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Trigemina Inc.

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