Migraine: Expanding our Tx arsenal

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Applied Evidence

Migraine: Expanding our Tx arsenal

J Fam Pract. 2019 January;68(1):10-14,16-24

By

Kathryn McGrath, MD

Allison Rague, MD

Claire Thesing, MD

Elizabeth Collins, MD

Olivia Seecof, MD

John Liantonio, MD

Beyond tried-and-true therapies are new therapeutic targets on the horizon—giving you a bigger toolbox to help patients abort and prevent migraine episodes.

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PRACTICE RECOMMENDATIONS

› Offer treatment with a triptan to adult patients with moderate-to-severe episodic migraine. A

› Consider prescribing topiramate, divalproex sodium, metoprolol, propranolol, or the herbal, Petasites hybridum, for the prevention of recurrent episodic migraine that has not responded to a reduction in headache triggers. A

› Add onabotulinumtoxinA injection to your therapeutic toolbox as an effective preventive treatment for chronic migraine (≥15 headache days a month for 3 months). B

› Recommend magnesium and feverfew as adjunctive preventive treatments for migraine. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

References

1. Stokes M, Becker WJ, Lipton RB, et al. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS). Headache. 2011;51:1058-1077.

2. Smitherman TA, Burch R, Sheikh H, et al. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013;53:427-436.

3. Burch RC, Loder S, Loder E, et al. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache. 2015;55:21-34.

4. Gooch CL, Pracht E, Borenstein AR. The burden of neurological disease in the United States: a summary report and call to action. Ann Neurol. 2017;81:479-484.

5. Ferrari MD, Klever RR, Terwindt GM, et al. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol. 2015;14:65-80.

6. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosc. 2015;35:6619-6629.

7. Maniyar FH, Sprenger T, Monteith T, et al. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain. 2013;137(Pt 1):232-241.

8. Cutrer FM, Sorensen AG, Weisskoff RM, et al. Perfusion‐weighted imaging defects during spontaneous migrainous aura. Ann Neurol. 1998;43:25-31.

9. Hadjikhani N, Sanchez Del Rio MS, Wu O, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A. 2001;98:4687-4692.

10. Pietrobon D, Moskowitz MA. Pathophysiology of migraine. Ann Rev Physiol. 2013;75:365-391.

11. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, (beta version). Cephalalgia. 2013;33:629-808.

12. Lipton RB, Dodick D, Sadovsky RE, et al; ID Migraine validation study. A self-administered screener for migraine in primary care: The ID Migraine^™ validation study. Neurology. 2003;61:375-382.

13. Láinez MJ, Domínguez M, Rejas J, et al. Development and validation of the Migraine Screen Questionnaire (MS‐Q). Headache. 2005;45:1328-1338.

14. Detsky ME, McDonald DR, Baerlocher MO, et al. Does this patient with headache have a migraine or need neuroimaging? JAMA. 2006;296:1274-1283.

15. Becker WJ, Findlay T, Moga C, et al. Guideline for primary care management of headache in adults. Can Fam Physician. 2015;61:670-679.

16. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55:754-762.

17. Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American Headache Society evidence assessment of migraine pharmacotherapies. Headache. 2015;55:3-20.

18. Voss T, Lipton RB, Dodick DW, et al. A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia. 2016;36:887-898.

19. Russo AF. Calcitonin gene-related peptide (CGRP): a new target for migraine. Annu Rev Pharmacol Toxicol. 2015;55:533-552.

20. Färkkilä M, Diener HC, Géraud G, et al; COL MIG-202 study group. Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. Lancet Neurol. 2012;11:405-413.

21. Pringsheim T, Davenport WJ, Marmura MJ, et al. How to apply the AHS evidence assessment of the acute treatment of migraine in adults to your patient with migraine. Headache. 2016;56:1194-1200.

22. Thorlund K, Mills EJ, Wu P, et al. Comparative efficacy of triptans for the abortive treatment of migraine: a multiple treatment comparison meta-analysis. Cephalalgia. 2014;34:258-267.

23. Law S, Derry S, Moore RA. Sumatriptan plus naproxen for acute migraine attacks in adults. Cochrane Database Syst Rev. 2013;(10):CD008541.

24. Orr SL, Aubé M, Becker WJ, et al. Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalalgia. 2015;35:271-284.

25. Ferrari MD, Goadsby PJ, Roon KI, et al. Triptans (serotonin, 5‐HT1B/1D agonists) in migraine: detailed results and methods of a meta‐analysis of 53 trials. Cephalalgia. 2002;22:633-658.

26. Goadsby PJ, Edvinsson L. The trigeminovascular system and migraine: studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats. Ann Neurol. 1993;33:48-56.

27. A phase 3, multicenter, randomized, double-blind, placebo-controlled single attack study to evaluate the efficacy, safety, and tolerability of oral ubrogepant in the acute treatment of migraine. https://clinicaltrials.gov/ct2/show/study/NCT02828020. Accessed November 16, 2018.

28. Rubio-Beltrán E, Labastida-Ramírez A, Villalón CM, et al. Is selective 5-HT_1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018;186:88-97.

29. Diener HC, Charles A, Goadsby PJ, et al. New therapeutic approaches for the prevention and treatment of migraine. Lancet Neurol. 2015;14:1010-1022.

30. Lipton RB, Silberstein SD. Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache. 2015;55 Suppl 2:103-122.

31. Martin PR. Behavioral management of migraine headache triggers: learning to cope with triggers. Curr Pain Headache Rep. 2010;14:221-227.

32. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN guidelines for prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache. 2012;52:930-945.

33. Dodick DW, Turkel CC, DeGryse RE, et al; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double‐blind, randomized, placebo‐controlled phases of the PREEMPT clinical program. Headache. 2010;50:921-936.

34. Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016(6):CD001218.

35. Varkey E, Cider Å, Carlsson J, et al. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia. 2011;31:1428-1438.

36. Guilbot A, Bangratz M, Abdellah SA, et al. A combination of coenzyme Q10, feverfew and magnesium for migraine prophylaxis: a prospective observational study. BMC Complement Altern Med. 2017;17:433.

37. Dalla Volta G, Zavarize P, Ngonga G, et al. Combination of Tanacethum partenium, 5-hydrossitriptophan (5-Http) and magnesium in the prophylaxis of episodic migraine without aura (AURASTOP^®) an observational study. Int J Neuro Brain Dis. 2017;4:1-4.

38. Puledda F, Goadsby PJ. An update on non‐pharmacological neuromodulation for the acute and preventive treatment of migraine. Headache. 2017;57:685-691.

39. Goadsby PJ, Reuter U, Hallström Y, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123-2132.

40. Reuter U. Efficacy and safety of erenumab in episodic migraine patients with 2-4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study. Abstract 009, AAN 2018 Annual Meeting; April 24, 2018.

41. Diener HC, Freitag FG, Danesch U. Safety profile of a special butterbur extract from Petasites hybridus in migraine prevention with emphasis on the liver. Cephalalgia Reports. https://journals.sagepub.com/doi/10.1177/2515816318759304. 2018 May 2. Accessed December 15, 2018.

42. Kingston WS, Halker R. Determinants of suboptimal migraine diagnosis and treatment in the primary care setting. J Clin Outcomes Manag. 2017;24:319-324.

43. Herd CP, Tomlinson CL, Rick C, et al. Botulinum toxins for the prevention of migraine in adults. Cochrane Database of Syst Rev. 2018;6:CD011616.

44. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology. 2004;63:2240-2244.

45. Von Luckner A, Riederer F. Magnesium in migraine prophylaxis—is there an evidence‐based rationale? A systematic review. Headache. 2018;58:199-209.

46. Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425-434.

47. Sonal Sekhar M, Sasidharan S, Joseph S, et al. Migraine management: How do the adult and paediatric migraines differ? Saudi Pharm J. 2012;20:1-7.

48. Lewis DW. Pediatric migraine. In: Lewis DW. Clinician’s Manual on Treatment of Pediatric Migraine. London, UK: Springer Healthcare Ltd; 2010:15-26.

49. Ho TW, Pearlman E, Lewis D, et al. Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized double-blind, placebo controlled trial using a novel adaptive enrichment design. Cephalagia. 2012;32:750-765.

50. Khrizman M, Pakalnis A. Management of pediatric migraine: current therapies. Pediatr Ann. 2018;47:e55-e60.

51. Lipton RB, Bigal ME, Diamond M, et al; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343-349.

52. Powers SW, Coffey CS, Chamberlin LA, et al; CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115-124.

53. Neut D, Fily A, Cuvellier JC, et al. The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents. J Headache Pain. 2012;13:61-65.

54. Ng QX, Venkatanarayanan N, Kumar L. A systematic review and meta‐analysis of the efficacy of cognitive behavioral therapy for the management of pediatric migraine. Headache. s2017;57:349-362.

55. Lipton RB, Baggish JS, Stewart WF, et al. Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Arch Intern Med. 2000;160:3486-3492.

56. Lucas S. Medication use in the treatment of migraine during pregnancy and lactation. Curr Pain Headache Rep. 2009;13:392-398.

57. Marchenko A, Etwel F, Olutunfesse O, et al. Pregnancy outcome following prenatal exposure to triptan medications: a meta-analysis. Headache. 2015:55:490-501.

58. Wells RE, Turner DP, Lee M, et al. Managing migraine during pregnancy and lactation. Curr Neurol Neurosci Rep. 2016;16:40.

59. Haan J, Hollander J, Ferrari MD. Migraine in the elderly: a review. Cephalalgia. 2007;27:97-106.

60. Gladstone JP, Eross EJ, Dodick DW. Migraine in special populations. Treatment strategies for children and adolescents, pregnant women, and the elderly. Postgrad Med. 2004;115:39-44,47-50.

Migraine is a highly disabling primary headache disorder that affects more than 44 million Americans annually.¹ The disorder causes pain, photophobia, phonophobia, and nausea that can last for hours, even days. Migraine headaches are 2 times more common in women than in men; although migraine is most common in people 30 to 39 years of age, all ages are affected.^2,3 Frequency of migraine headache is variable; chronic migraineurs experience more than 15 headache days a month.

^{©Cath Riley/Science Source}

Recent estimates indicate that the cost of acute and chronic migraine headaches reaches approximately $78 million a year in the United States. ⁴ This high burden of disease has made effective migraine treatment options absolutely essential. Recent advances in our understanding of migraine pathophysiology have led to new therapeutic targets; there are now many novel treatment approaches on the horizon.

In this article, we review the diagnosis and management of migraine in detail. Our emphasis is on evidence-based approaches to acute and prophylactic treatment, including tried-and-true options and newly emerging therapies.

Neuronal dysfunction and a genetic predisposition

Although migraine was once thought to be caused by abnormalities of vasodilation, current research suggests that the disorder has its origins in primary neuronal dysfunction. There appears to be a genetic predisposition toward widespread neuronal hyperexcitability in migraineurs.⁵ In addition, hypothalamic neurons are thought to initiate migraine by responding to changes in brain homeostasis. Increased parasympathetic tone might activate meningeal pain receptors or lower the threshold for transmitting pain signals from the thalamus to the cortex.⁶

Prodromal symptoms and aura appear to originate from multiple areas across the brain, including the hypothalamus, cortex, limbic system, and brainstem. This widespread brain involvement might explain why some headache sufferers concurrently experience a variety of symptoms, including fatigue, depression, muscle pain, and an abnormal sensitivity to light, sound, and smell.^6,7

After taking the initial history (headache onset, location, duration, associated symptoms), focus attention on assessing the risk of intracranial pathology.

Although the exact mechanisms behind each of these symptoms have yet to be defined precisely, waves of neuronal depolarization—known as cortical spreading depression—are suspected to cause migraine aura.^8-10 Cortical spreading depression activates the trigeminal pain pathway and leads to the release of pro-inflammatory markers such as calcitonin gene-related protein (CGRP).⁶ A better understanding of these complex signaling pathways has helped provide potential therapeutic targets for new migraine drugs.

Diagnosis: Close patient inquiry is most helpful

The International Headache Society (IHS) criteria for primary headache disorders serve as the basis for the diagnosis of migraine and its subtypes, which include migraine without aura and migraine with aura. Due to variability of presentation, migraine with aura is further subdivided into migraine with typical aura (with and without headache), migraine with brainstem aura, hemiplegic migraine, and retinal migraine.¹¹

Continue to: How is migraine defined?