Skip to content


Volume 16 Supplement 1

1st Joint ANIRCEF-SISC Congress

  • Invited speaker presentation
  • Open Access

Chronic migraine: treatability, refractoriness, pseudo-refractoriness

  • 1Email author,
  • 1,
  • 1,
  • 1 and
  • 1
The Journal of Headache and Pain201516 (Suppl 1) :A39

  • Published:


  • Gabapentin
  • Topiramate
  • Personality Disorder
  • Memantine
  • Pregabalin

Chronic migraine (CM), a highly disabling condition affecting 2-3% of the general population, represents a difficult-to-treat disorder for its unclear pathophysiology, complex comorbidities, and disappointing response to available pharmacological treatments[1]. High quality evidence (≥2 RCTs) recommends the prophylactic use of onabotulinum toxin A (155-195 IU) and topiramate (100 mg) in CM, while lower quality evidence (1 RCT) supports the treatment with sodium valproate (800-1500 mg), gabapentin (2400 mg) and tizanidine (18 mg)[2]. Amitriptyline, memantine, zonisamide and pregabalin may also be of help in CM but their use has been suggested only in open studies[2]. CM patients may show poor or no response to preventative therapies. The consensus statement of the European Headache Federation (EHF) defines CM refractory to treatment (rCM) when it does not respond to adequate dosages of at least 3 drugs from the classes of beta-blockers, anticonvulsants, tricyclics, onabotulinum toxin A and others (e.g., flunarizine, candesartan) for at least 3 months each, in absence of medication overuse[3]. This rCM definition has been questioned by some authors who stressed the need of using drugs from different classes, not limited to 3, before making rCM diagnosis[4]. Labeling a patient as affected by rCM may profoundly modify his/her life with heavy psychological, social, work and medico-legal consequences, potentially leading to expensive and still unsatisfying surgical procedures such as occipital nerve stimulation[5]. We point out the risk that the current rCM EHF definition could indeed also include pseudo-refractory CM patients, due to potential bias: firstly, a significant proportion of CM patients may spontaneously reverse to episodic migraine, as clearly evidenced in population-based study[6]; secondly, rCM patients may present underlying psychiatric disturbances (e.g., personality disorders) not easily recognized, classified and treated by headache specialists; thirdly, rCM diagnosis could be biased by unproven evidence as current rCM criteria do not specify who should attest patient's previous headache history (theoretically self-reported or stated by unqualified physicians). We suggest that 1) rCM is probably more rare than presently stated; 2) before formulating a diagnosis of rCM, psychiatric disorders should be carefully ruled out by appropriate and thorough psychiatric investigations; 3) when assessing CM patient's past medical history, only clinical data coming from certified headache centers should be considered; 4) CM patients should be followed up for an adequate period of time before making a definite rCM diagnosis.

Authors’ Affiliations

Headache and Pain Unit, Department of Neurological Motor and Sensorial Sciences, IRCCS San Raffaele Pisana, Rome, Italy


  1. Buse DC, Manack A, Serrano D, Turkel C, Lipton RB: Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry. 2010, 81 (4): 428-32. 10.1136/jnnp.2009.192492.View ArticlePubMedGoogle Scholar
  2. Schwedt TJ: Chronic migraine. BMJ. 2014, 348: g1416-10.1136/bmj.g1416.View ArticlePubMedGoogle Scholar
  3. Martelletti P, Katsarava Z, Lampl C, Magis D, Bendtsen L, Negro A, Russell MB, Mitsikostas DD, Jensen RH: Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain. 2014, 15: 47-10.1186/1129-2377-15-47. doi: 10.1186/1129-2377-15-47PubMed CentralView ArticlePubMedGoogle Scholar
  4. Wöber C, Wessely P: Austrian Consensus Group on Refractory Chronic Migraine: Comment on: Martelletti et al. Refractory chronic migraine: a consensus statement on clinical definition from the European Headache Federation. J Headache Pain. 2014, 15: 77-10.1186/1129-2377-15-77. doi: 10.1186/1129-2377-15-77PubMed CentralView ArticlePubMedGoogle Scholar
  5. Magis D, Schoenen J: Advances and challenges in neurostimulation for headaches. Lancet Neurol. 2012, 11: 708-19. 10.1016/S1474-4422(12)70139-4.View ArticlePubMedGoogle Scholar
  6. Bigal ME, Lipton RB: The prognosis of migraine. Curr Opin Neurol. 2008, 21 (3): 301-8. 10.1097/WCO.0b013e328300c6f5.View ArticlePubMedGoogle Scholar


© Barbanti et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Please note that comments may be removed without notice if they are flagged by another user or do not comply with our community guidelines.