Neurol. praxi. 2025;26(6):477-481 | DOI: 10.36290/neu.2025.030

Resistant and refractory migraine

MUDr. Andrea Bártková, Ph.D.
Neurologická klinika LF UP a FN v Olomouci

The author in the article presents current definitions of resistant, refractory migraines and treatment failure in relation to recent migraine therapeutic options and their implementation in clinical practice.

Keywords: resistant, refractory migraine, migraine prophylaxy, anti-CGRP monoclonal antibodies, gepants, onabotulinumtoxin A, non-pharmacological treatment.

Received: February 26, 2025; Revised: March 31, 2025; Accepted: March 31, 2025; Prepublished online: March 31, 2025; Published: December 15, 2025  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Bártková A. Resistant and refractory migraine. Neurol. praxi. 2025;26(6):477-481. doi: 10.36290/neu.2025.030.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Purchase PDF - 60 CZK (2.5 EUR)
    will be unlocked 15.12.2026

    References

    1. Ahmed F, Gaul C, García-Moncó JC, et al. Investigators R.P. An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study. J Headache Pain. 2019;20(1):26. doi: 10.1186/s10194-019-0976-1. Go to original source... Go to PubMed...
    2. Al-Karagholi MA, Kalatharan V, Ghanizada H, et al. Prolactin in headache and migraine: a systematic review of preclinical studies. Headache. 2023;63(5):577-584. doi: 10.1111/head.14412. Go to original source... Go to PubMed...
    3. Ailani J, Lipton RB, Goadsby PJ, et al. Atogepant for the preventive treatment of migraine. N Engl J Med. 2021;385(8):695-706. doi: 10.1056/NEJMoa2035908. Go to original source... Go to PubMed...
    4. Andreou AP, Edvinsson L. Mechanisms of migraine as a chronic evolutive condition. J Headache Pain. 2019;20(1):117. doi: 10.1186/s10194-019-1066-0. Go to original source... Go to PubMed...
    5. Ashina M, Goadsby PJ, Reuter U, et al. Long-term efficacy and safety of erenumab in migraine prevention: results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur J Neurol. 2021;28(5):1716-1725. doi: 10.1111/ene.14715. Go to original source... Go to PubMed...
    6. Ashina M, Lanteri-Minet M, Pozo-Rosich P, et al. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2022;21(7):597-607. doi: 10.1016/S1474-4422(22)00185-5. Go to original source... Go to PubMed...
    7. Dyhring T, Jansen-Olesen I, Christophersen P, et al. Pharmacological profiling of K(ATP) channel modulators: an outlook for new treatment opportunities for migraine. Pharmaceuticals. 2023;16(2) doi: 10.3390/ph16020225. Go to original source... Go to PubMed...
    8. Edvinsson L, Haanes KA, Warfvinge K, et al. CGRP as the target of new migraine therapies - successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338-350. doi: 10.1038/s41582-018-0003-1. Go to original source... Go to PubMed...
    9. Ehrlich M, Hentschke C, Sieder C, et al. Erenumab versus topiramate: post hoc efficacy analysis from the HER-MES study. J Headache Pain. 2022;23(1):141. doi: 10.1186/s10194-022-01511-y. Go to original source... Go to PubMed...
    10. Ferrari MD, Diener HC, Ning X, et al. Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial. Lancet. 2019;394(10203):1030-1040. doi: 10.1016/S0140-6736(19)31946-4. Go to original source... Go to PubMed...
    11. Greco R, Demartini C, Zanaboni AM, et al. The endocannabinoid system and related lipids as potential targets for the treatment of migraine-related pain. Headache. 2022;62(3):227-240. doi: 10.1111/head.14267. Go to original source... Go to PubMed...
    12. Hepp Z, Dodick DW, Varon SF, et al. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalalgia. 2017;37(5):470-485. doi: 10.1177/0333102416678382. Go to original source... Go to PubMed...
    13. Chalmer MA, Rasmussen AH, Kogelman LJA., et al. Chronic migraine: genetics or environment? Eur J Neurol. 2021;28(5):1726-1736. doi: 10.1111/ene.14724. Go to original source... Go to PubMed...
    14. Ihara K, Ohtani S, Watanabe N, et al. Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study. J Headache Pain. 2023;24(1):23. doi: 10.1186/s10194-023-01556-7. Go to original source... Go to PubMed...
    15. International Classification of Headache Disorders. 3rd edition. Cephalalgia. 2018;38(1):1-211. Go to original source...
    16. Iyengar S, Johnson KW, Ossipov MH, et al. CGRP and the trigeminal system in migraine. Headache. 2019;59(5):659-681. doi: 10.1111/head.13529. Go to original source... Go to PubMed...
    17. Jackson JL, Cogbill E, Santana-Davila R, et al. A comparative effectiveness meta-analysis of drugs for the prophylaxis of migraine headache. PLoS One. 2015;10(7) doi: 10.1371/journal.pone.0130733. Go to original source... Go to PubMed...
    18. Kuner R, Flor H. Structural plasticity and reorganisation in chronic pain. Nat Rev Neurosci. 2016;18(1):20-30. doi: 10.1038/nrn.2016.162. Go to original source... Go to PubMed...
    19. Luykx J, Mason M, Ferrari MD, et al. Are migraineurs at increased risk of adverse drug responses? A meta-analytic comparison of topiramate-related adverse drug reactions in epilepsy and migraine. Clin Pharmacol Ther. 2009;85(3):283-288. doi: 10.1038/clpt.2008.203. Go to original source... Go to PubMed...
    20. Mitsikostas DD. Nocebo in headache. Curr Opin Neurol. 2016;29(3):331-336. doi: 10.1097/WCO.0000000000000313. Go to original source... Go to PubMed...
    21. Mulleners WM, Kim BK, Láinez MJA, et al. Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Lancet Neurol. 2020;19(10):814-825. doi: 10.1016/S1474-4422(20)30279-9. Go to original source... Go to PubMed...
    22. Negro A, Martelletti P. Gepants for the treatment of migraine. Expert Opin Investig Drugs. 2019;28(6):555-567. doi: 10.1080/13543784.2019.1618830. Go to original source... Go to PubMed...
    23. Ornello R, Andreou AP, De Matteis E, et al. Resistant and refractory migraine: clinical presentation, pathophysiology, and management. E Biom. 2024 Jan:99:104943. doi: 10.1016/j.ebiom.2023.104943. Go to original source... Go to PubMed...
    24. Ornello R, Ripa P, Pistoia F, et al. Migraine and body mass index categories: a systematic review and metaanalysis of observational studies. J Headache Pain. 2015;16:27 Go to original source...
    25. Park CG, Chu MK. Interictal plasma glutamate levels are elevated in individuals with episodic and chronic migraine. Sci Rep. 2022;12(1):6921. doi: 10.1038/s41598-022-10883-9. Go to original source... Go to PubMed...
    26. Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013;310(24):2622-2630. doi: 10.1001/jama.2013.282533. Go to original source... Go to PubMed...
    27. Pozo-Rosich P, Ailani J, Ashina M, et al. Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;402:775. doi: 10.1016/S0140-6736(23)01049-8. Go to original source... Go to PubMed...
    28. Raffaelli B, Kalantzis R, Mecklenburg J, et al. Erenumab in chronic migraine patients who previously failed five first-line oral prophylactics and OnabotulinumtoxinA: a dual-center retrospective observational study. Front Neurol. 2020;11:417. doi: 10.3389/fneur.2020.00417. Go to original source... Go to PubMed...
    29. Reuter U, Ehrlich M, Gendolla A, et al. Erenumab versus topiramate for the prevention of migraine-a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia. 2021;42 doi: 10.1177/03331024211053571. Go to original source... Go to PubMed...
    30. Reuter U, Ehlich M, Gendolla A, et al. Erenumab versus topiramate for the prevention of migraine - a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia. 2022 Feb;42(2):108-118. doi: 10.1177/03331024211053571. Go to original source... Go to PubMed...
    31. Reuter U, Goadsby PJ, Lanteri-Minet M, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280-2287. doi: 10.1016/S0140-6736(18)32534-0. Go to original source... Go to PubMed...
    32. Sacco S, Amin FM, Ashina M, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update. J Headache Pain. 2022;23(1):67. doi: 10.1186/s10194-022-01431-x. Go to original source... Go to PubMed...
    33. Sacco S, Braschinski M, Ducros A, et al. European headache federation consensus on definition of resistant and refraktory migraine" developer with endorsement of the European Migraine and Headache Alliance (EMHA). J Headahe Pain. 2020;21(1):76. Go to original source...
    34. Santoro JD, Moon PK, Han M, et al. Early onset diffusion abnormalities in refractory headache disorders. Front Neurol. 2022;13 doi: 10.3389/fneur.2022.898219. Go to original source... Go to PubMed...
    35. Scuteri D, Tonin P, Nicotera P, et al. Pooled analysis of real-world evidence supports anti-CGRP mAbs and OnabotulinumtoxinA combined trial in chronic migraine. Toxins. 2022;14(8) doi: 10.3390/toxins14080529. Go to original source... Go to PubMed...
    36. Schulte LH, Allers A, May A. Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology. 2017;88(21):2011-2016. doi: 10.1212/WNL.0000000000003963 Go to original source... Go to PubMed...
    37. Strother LC, Srikiatkhachorn A, Supronsinchai W. Targeted orexin and hypothalamic neuropeptides for migraine. Neurotherapeutics. 2018;15(2):377-390. doi: 10.1007/s13311-017-0602-3. 30. Go to original source... Go to PubMed...

    Return to the content


    Neurology for Practice

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.