title: Emerging treatment for chronic migraine and refractory chronic migraine.
abstract: BACKGROUND
  Chronic migraine (CM), the suffering of 15 or more headache days with at least 8 of these migraine days, afflicts 1.3% - 5.1% of the global population. CM is the most common disorder faced by experts in tertiary headache centers. When resistant to conventional medical treatment and prophylactic medication this condition is known as refractory chronic migraine (RCM). RCM is one of the greatest challenges in headache medicine.
  
  
  METHODS
  State-of-the-art and future medical treatments of chronic migraine include: OnabotulinumtoxinA, antiepileptic drugs (Levetiracetam, Magnesium valproate hydrate, Lacosamide, BGG-492), 5-HT agonists (Lasmiditan, NXN-188, novel delivery systems of Sumatriptan, a well-established drug treatment for acute migraine), CGRP receptor antagonists (BMS-927711), ML-1 agonists (Ramelteon), orexin receptor antagonist (MK-6096), plant-derived compound (LLL-2011) and other multitarget drugs such as Tezampanel, Tonabersat, intranasal carbon dioxide and BOL-148. The role for neuromodulation, the application of targeted electrical stimulation, will be examined.
  
  
  CONCLUSIONS
  Medication overuse headache (MOH) is now recognized to be a major factor in many cases of both chronic and refractory chronic migraine. MOH must be addressed prior to evaluating the effectiveness of new preventative and prophylactic treatment approaches. Innovative new drugs and electrical neuromodulation are promising CM treatments. Future studies must carefully screen patients and acquire data that can lead to personalized, tailored treatment strategies.
authors.affiliation: Sapienza University and Advanced Molecular Diagnostic Unit, Sant'Andrea Hospital, NESMOS Department, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.forename: Andrea
authors.initials: A
authors.lastname: Negro
authors.forename: Stefano
authors.initials: S
authors.lastname: Palmisani
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gentile
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Fiore
authors.forename: Marco
authors.initials: M
authors.lastname: Mercieri
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.forename: Thomas
authors.initials: T
authors.lastname: Smith
authors.forename: Adnan
authors.initials: A
authors.lastname: Al-Kaisy
authors.forename: Roberto
authors.initials: R
authors.lastname: Arcioni
authors.forename: Paolo
authors.initials: P
authors.lastname: Martelletti
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D055808:Drug Discovery; D006801:Humans; D038801:International Classification of Diseases; D008881:Migraine Disorders / Q000145:classification / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D044122:Receptor, Melatonin, MT1 / Q000819:agonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D044122:Receptor, Melatonin, MT1; D017366:Serotonin Receptor Agonists; D019274:Botulinum Toxins, Type A