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Preventive treatment of migraine in adults

Zahid H Bajwa, MD
Jonathan H Smith, MD
Section Editor
Jerry W Swanson, MD, MHPE
Deputy Editor
John F Dashe, MD, PhD


Migraine is a common disorder that affects approximately 17 percent of women and 6 percent of men. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Epidemiology'.)

The preventive treatment of episodic migraine headache in adults is reviewed here. The clinical features and management of chronic migraine are discussed separately. (See "Chronic migraine".)

Other aspects of migraine are reviewed elsewhere. (See "Acute treatment of migraine in adults" and "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults".)


Many migraine sufferers can benefit from preventive migraine treatment. Indications include the following [1-5]:

Frequent or long lasting migraine headaches

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Literature review current through: Nov 2017. | This topic last updated: Dec 12, 2017.
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  1. 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.
  2. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012; 78:1337.
  3. Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol 2009; 16:968.
  4. Pringsheim T, Davenport W, Mackie G, et al. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci 2012; 39:S1.
  5. MacGregor EA. In the clinic. Migraine. Ann Intern Med 2013; 159:ITC5.
  6. Loder E, Biondi D. General principles of migraine management: the changing role of prevention. Headache 2005; 45 Suppl 1:S33.
  7. Goadsby PJ, Lipton RB, Ferrari MD. Migraine--current understanding and treatment. N Engl J Med 2002; 346:257.
  8. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia 2002; 22:491.
  9. Buse DC, Manack A, Serrano D, et al. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry 2010; 81:428.
  10. Pringsheim T, Davenport WJ, Becker WJ. Prophylaxis of migraine headache. CMAJ 2010; 182:E269.
  11. Shamliyan TA, Choi JY, Ramakrishnan R, et al. Preventive pharmacologic treatments for episodic migraine in adults. J Gen Intern Med 2013; 28:1225.
  12. Law M, Morris JK, Jordan R, Wald N. Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo-controlled trials with 24,000 participants. Circulation 2005; 112:2301.
  13. Linde K, Rossnagel K. Propranolol for migraine prophylaxis. Cochrane Database Syst Rev 2004; :CD003225.
  14. Limmroth V, Michel MC. The prevention of migraine: a critical review with special emphasis on beta-adrenoceptor blockers. Br J Clin Pharmacol 2001; 52:237.
  15. Rosen JA. Observations on the efficacy of propranolol for the prophylaxis of migraine. Ann Neurol 1983; 13:92.
  16. Solomon GD, Steel JG, Spaccavento LJ. Verapamil prophylaxis of migraine. A double-blind, placebo-controlled study. JAMA 1983; 250:2500.
  17. Markley HG, Cheronis JC, Piepho RW. Verapamil in prophylactic therapy of migraine. Neurology 1984; 34:973.
  18. Tfelt-Hansen P. Prophylactic pharmacotherapy of migraine. Some practical guidelines. Neurol Clin 1997; 15:153.
  19. Jónsdóttir M, Meyer JS, Rogers RL. Efficacy, side effects and tolerance compared during headache treatment with three different calcium blockers. Headache 1987; 27:364.
  20. Schrader H, Stovner LJ, Helde G, et al. Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study. BMJ 2001; 322:19.
  21. Tronvik E, Stovner LJ, Helde G, et al. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA 2003; 289:65.
  22. Banzi R, Cusi C, Randazzo C, et al. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults. Cochrane Database Syst Rev 2015; 4:CD002919.
  23. Chronicle E, Mulleners W. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev 2004; :CD003226.
  24. Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004; 291:965.
  25. Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 2004; 61:490.
  26. Diener HC, Bussone G, Van Oene JC, et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia 2007; 27:814.
  27. Diener HC, Agosti R, Allais G, et al. Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2007; 6:1054.
  28. Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013; :CD010610.
  29. Linde M, Mulleners WM, Chronicle EP, McCrory DC. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013; :CD010611.
  30. FDA Drug Safety Communication: Valproate anti-seizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. www.fda.gov/Drugs/DrugSafety/ucm350684.htm (Accessed on May 15, 2013).
  31. Linde M, Mulleners WM, Chronicle EP, McCrory DC. Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013; :CD010609.
  32. Silberstein S, Goode-Sellers S, Twomey C, et al. Randomized, double-blind, placebo-controlled, phase II trial of gabapentin enacarbil for migraine prophylaxis. Cephalalgia 2013; 33:101.
  33. Holland S, Silberstein SD, Freitag F, et al. Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012; 78:1346.
  34. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache 2000; 40:445.
  35. Evers S, Vollmer-Haase J, Schwaag S, et al. Botulinum toxin A in the prophylactic treatment of migraine--a randomized, double-blind, placebo-controlled study. Cephalalgia 2004; 24:838.
  36. Elkind AH, O'Carroll P, Blumenfeld A, et al. A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis. J Pain 2006; 7:688.
  37. Naumann M, So Y, Argoff CE, et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2008; 70:1707.
  38. Bravo TP, Vargas BB. Migraine preventative butterbur has safety concerns. Neurology Times. http://www.neurologytimes.com/headache-and-migraine/migraine-preventative-butterbur-has-safety-concerns (Accessed on August 10, 2015).
  39. Grossmann M, Schmidramsl H. An extract of Petasites hybridus is effective in the prophylaxis of migraine. Int J Clin Pharmacol Ther 2000; 38:430.
  40. Diener HC, Rahlfs VW, Danesch U. The first placebo-controlled trial of a special butterbur root extract for the prevention of migraine: reanalysis of efficacy criteria. Eur Neurol 2004; 51:89.
  41. Lipton RB, Göbel H, Einhäupl KM, et al. Petasites hybridus root (butterbur) is an effective preventive treatment for migraine. Neurology 2004; 63:2240.
  42. Dodick DW, Goadsby PJ, Spierings EL, et al. Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014; 13:885.
  43. Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014; 13:1100.
  44. Bigal ME, Dodick DW, Rapoport AM, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol 2015; 14:1081.
  45. Sun H, Dodick DW, Silberstein S, et al. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol 2016; 15:382.
  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.
  47. Goadsby PJ, Reuter U, Hallström Y, et al. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med 2017; 377:2123.
  48. Tepper SJ, Rapoport A, Sheftell F. The pathophysiology of migraine. Neurologist 2001; 7:279.
  49. Sándor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005; 64:713.
  50. Wider B, Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2015; 4:CD002286.
  51. Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed) 1985; 291:569.
  52. Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet 1988; 2:189.
  53. Palevitch D, Earon G, Carasso R. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: a double-blind placebo-controlled study. Phytotherapy Research 1997; 11:508.
  54. Diener HC, Pfaffenrath V, Schnitker J, et al. Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine prevention--a randomized, double-blind, multicentre, placebo-controlled study. Cephalalgia 2005; 25:1031.
  55. De Weerdt CJ, Bootsma HP, Hendriks H. Herbal medicines in migraine prevention Randomized double-blind placebo-controlled crossover trial of a feverfew preparation. Phytomedicine 1996; 3:225.
  56. Pfaffenrath V, Diener HC, Fischer M, et al. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind, multicentre, randomized placebo-controlled dose-response study. Cephalalgia 2002; 22:523.
  57. Teigen L, Boes CJ. An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine. Cephalalgia 2015; 35:912.
  58. Facchinetti F, Sances G, Borella P, et al. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991; 31:298.
  59. Peikert A, Wilimzig C, Köhne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996; 16:257.
  60. Köseoglu E, Talaslioglu A, Gönül AS, Kula M. The effects of magnesium prophylaxis in migraine without aura. Magnes Res 2008; 21:101.
  61. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia 1996; 16:436.
  62. Alstadhaug KB, Odeh F, Salvesen R, Bekkelund SI. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 2010; 75:1527.
  63. Gonçalves AL, Martini Ferreira A, Ribeiro RT, et al. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016; 87:1127.
  64. Lindegaard KF, Ovrelid L, Sjaastad O. Naproxen in the prevention of migraine attacks. A double-blind placebo-controlled cross-over study. Headache 1980; 20:96.
  65. Ziegler DK, Ellis DJ. Naproxen in prophylaxis of migraine. Arch Neurol 1985; 42:582.
  66. Welch KM, Ellis DJ, Keenan PA. Successful migraine prophylaxis with naproxen sodium. Neurology 1985; 35:1304.
  67. Sargent J, Solbach P, Damasio H, et al. A comparison of naproxen sodium to propranolol hydrochloride and a placebo control for the prophylaxis of migraine headache. Headache 1985; 25:320.
  68. Sances G, Martignoni E, Fioroni L, et al. Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. Headache 1990; 30:705.
  69. Gray RN, Goslin RE, McCrory DC, et al. Drug treatments for the prevention of migraine headache. Rockville (MD): Agency for Health Care Policy and Research (US); 1999. http://www.ncbi.nlm.nih.gov/books/NBK45457/ (Accessed on April 30, 2012).
  70. Stensrud P, Sjaastad O. Clinical trial of a new anti-bradykinin, anti-inflammatory drug, ketoprofen (19.583 r.p.) in migraine prophylaxis. Headache 1974; 14:96.
  71. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998; 50:466.
  72. Buettner C, Nir RR, Bertisch SM, et al. Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Ann Neurol 2015; 78:970.
  73. Mauskop A. Nonmedication, alternative, and complementary treatments for migraine. Continuum (Minneap Minn) 2012; 18:796.
  74. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia 2011; 31:1428.
  75. Ahn AH. Why does increased exercise decrease migraine? Curr Pain Headache Rep 2013; 17:379.
  76. Holroyd KA, Cottrell CK, O'Donnell FJ, et al. Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial. BMJ 2010; 341:c4871.
  77. Martin PR. Behavioral management of migraine headache triggers: learning to cope with triggers. Curr Pain Headache Rep 2010; 14:221.
  78. Diener HC. Acupuncture for the treatment of headaches: more than sticking needles into humans? Cephalalgia 2008; 28:911.
  79. Li Y, Zheng H, Witt CM, et al. Acupuncture for migraine prophylaxis: a randomized controlled trial. CMAJ 2012; 184:401.
  80. Molsberger A. The role of acupuncture in the treatment of migraine. CMAJ 2012; 184:391.
  81. Meissner K, Fässler M, Rücker G, et al. Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. JAMA Intern Med 2013; 173:1941.
  82. Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev 2016; :CD001218.
  83. Linde K, Streng A, Jürgens S, et al. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005; 293:2118.
  84. Diener HC, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol 2006; 5:310.
  85. Kaptchuk TJ. Placebo studies and ritual theory: a comparative analysis of Navajo, acupuncture and biomedical healing. Philos Trans R Soc Lond B Biol Sci 2011; 366:1849.
  86. Kerr CE, Shaw JR, Conboy LA, et al. Placebo acupuncture as a form of ritual touch healing: a neurophenomenological model. Conscious Cogn 2011; 20:784.
  87. Schoenen J, Vandersmissen B, Jeangette S, et al. Migraine prevention with a supraorbital transcutaneous stimulator: a randomized controlled trial. Neurology 2013; 80:697.
  88. Martin PR. Managing headache triggers: think 'coping' not 'avoidance'. Cephalalgia 2010; 30:634.
  89. Martin PR, Reece J, Callan M, et al. Behavioral management of the triggers of recurrent headache: a randomized controlled trial. Behav Res Ther 2014; 61:1.
  90. Guyuron B, Reed D, Kriegler JS, et al. A placebo-controlled surgical trial of the treatment of migraine headaches. Plast Reconstr Surg 2009; 124:461.
  91. Mathew PG. A critical evaluation of migraine trigger site deactivation surgery. Headache 2014; 54:142.
  92. Diener HC, Bingel U. Surgical treatment for migraine: Time to fight against the knife. Cephalalgia 2015; 35:465.
  93. Dowson A, Mullen MJ, Peatfield R, et al. Migraine Intervention With STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation 2008; 117:1397.
  94. Mattle HP, Evers S, Hildick-Smith D, et al. Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial. Eur Heart J 2016; 37:2029.
  95. Schwedt TJ, Demaerschalk BM, Dodick DW. Patent foramen ovale and migraine: a quantitative systematic review. Cephalalgia 2008; 28:531.
  96. Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL. Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons. Lancet 2000; 356:1648.
  97. Schwerzmann M, Wiher S, Nedeltchev K, et al. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology 2004; 62:1399.
  98. Post MC, Thijs V, Herroelen L, Budts WI. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology 2004; 62:1439.
  99. Reisman M, Christofferson RD, Jesurum J, et al. Migraine headache relief after transcatheter closure of patent foramen ovale. J Am Coll Cardiol 2005; 45:493.
  100. Azarbal B, Tobis J, Suh W, et al. Association of interatrial shunts and migraine headaches: impact of transcatheter closure. J Am Coll Cardiol 2005; 45:489.
  101. Giardini A, Donti A, Formigari R, et al. Transcatheter patent foramen ovale closure mitigates aura migraine headaches abolishing spontaneous right-to-left shunting. Am Heart J 2006; 151:922.e1.
  102. Anzola GP, Frisoni GB, Morandi E, et al. Shunt-associated migraine responds favorably to atrial septal repair: a case-control study. Stroke 2006; 37:430.
  103. Mortelmans K, Post M, Thijs V, et al. The influence of percutaneous atrial septal defect closure on the occurrence of migraine. Eur Heart J 2005; 26:1533.
  104. Yankovsky AE, Kuritzky A. Transformation into daily migraine with aura following transcutaneous atrial septal defect closure. Headache 2003; 43:496.
  105. Rodés-Cabau J, Molina C, Serrano-Munuera C, et al. Migraine with aura related to the percutaneous closure of an atrial septal defect. Catheter Cardiovasc Interv 2003; 60:540.