Chronic migraine: treatability, refractoriness, pseudo-refractoriness.

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.