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Role of Antiepileptic Drugs as Preventive Agents for Migraine

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Abstract

Migraine is a common neurological disease affecting about 12% of the population in Western Europe and North America, and causing a considerable burden both to migraineurs and to society. Severe, frequent and disabling migraine attacks, as well as those poorly responsive to acute care medication, require preventive treatment, which is often under-utilized. Antiepileptic drugs are used in the prevention of migraine.

We performed a literature search of PubMed through June 2008 for controlled trials of antiepileptic drugs in the prevention of migraine. The search identified 70 papers for a full-text review. The majority of these papers referred to valproate and topiramate, and showed that these drugs are effective and well tolerated in migraine prevention and are suitable for first-line clinical use. On the other hand, acetazolamide, lamotrigine, oxcarbazepine and vigabatrin have been shown to be not effective and gabapentin requires further evaluation. For the rest of the antiepileptic drugs, no data from controlled trials are available.

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References

  1. Rasmussen BK. Epidemiology of headache. Cephalalgia 1995; 15: 45–68

    PubMed  CAS  Google Scholar 

  2. Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001; 41: 646–57

    Article  PubMed  CAS  Google Scholar 

  3. Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007; 68: 343–9

    Article  PubMed  CAS  Google Scholar 

  4. Ferrari MD. The economic burden of migraine to society. Pharmacoeconomics 1998; 13: 667–76

    Article  PubMed  CAS  Google Scholar 

  5. Michel P, Dartigues JF, Lindousli A, et al. Loss of productivity and quality of life in migraineurs among French workers: results from the GAZEL cohort. Headache 1997; 37: 71–8

    Article  PubMed  CAS  Google Scholar 

  6. Scher AI, Stewart WF, Lipton RB. Migraine and headache: a meta-analytic approach. In: Crombie IK, editor. Epidemiology of pain. Seattle (WA): IASP Press, 1999: 159–70

    Google Scholar 

  7. Rapoport AM. Acute and prophylactic treatments for migraine: present and future. Neurol Sci 2008 May; 29Suppl. 1: S110–22

    Article  PubMed  Google Scholar 

  8. Mulleners WM, Cronicle EP. Anticonvulsants in migraine prophylaxis: a Cochrane review. Cephalalgia 2008; 28: 585–97

    Article  PubMed  CAS  Google Scholar 

  9. Evers S, Afra J, Frese A, et al. EFNS guideline on the drug treatment of migraine: report of an EFNS task force. Eur J Neurol 2006 Jun; 13(6): 560–72

    Article  PubMed  CAS  Google Scholar 

  10. 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: 754–62

    CAS  Google Scholar 

  11. Bigal ME, Krymchantowski AV, Rapoport AM. New developments in migraine prophylaxis. Expert Opin Pharmacother 2003; 4(4): 1–11

    Article  Google Scholar 

  12. Lipton RB, Stewart WF. Prevalence and impact of migraine. Neurologic Clinics 1997; 15: 1–13

    Article  PubMed  CAS  Google Scholar 

  13. White HS. Mechanisms of action of the antiepileptic drugs valproic acid, gabapentin and topiramate: implications for the prophylactic management of migraine. In: Olesen J, Silberstein SD, Tfelt-Hansen P, editors. Preventive pharmacotherapy of headache disorders. Oxford: Oxford University Press, 2004: 79–88

    Google Scholar 

  14. Mathew NT, Saper JR, Silberstein SD, et al. Migraine prophylaxis with divalproex. Arch Neurol 1995; 52(3): 281–6

    Article  PubMed  CAS  Google Scholar 

  15. Klapper J. Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia 1997; 17(2): 103–8

    Article  PubMed  CAS  Google Scholar 

  16. Freitag FG, Collins SD, Carlson HA, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology 2002; 58(11): 1652–9

    Article  PubMed  CAS  Google Scholar 

  17. Hering R, Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 1992; 12(2): 81–4

    Article  PubMed  CAS  Google Scholar 

  18. Jensen R, Brinck T, Olesen J. Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study. Neurology 1994; 44(4): 647–51

    Article  PubMed  CAS  Google Scholar 

  19. Mitsikostas DD, Polychronidis I. Valproate versus flunarizine in migraine prophylaxis: a randomized, double-open, clinical trial. Funct Neurol 1997; 12(5): 267–76

    PubMed  CAS  Google Scholar 

  20. Kaniecki RG. A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Arch Neurol 1997; 54(9): 1141–5

    Article  PubMed  CAS  Google Scholar 

  21. Shaygannejad V, Janghorbani M, Ghorbani A, et al. Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study. Headache 2006; 46(4): 642–8

    Article  PubMed  Google Scholar 

  22. Millán-Guerrero RO, Isais-Millán R, Barreto-Vizcaíno S, et al. Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a randomized, controlled, double-blind study. Eur J Neurol 2007; 14(10): 1079–84

    Article  PubMed  Google Scholar 

  23. Blumenfeld AM, Schim JD, Chippendale TJ. Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache 2008; 48(2): 210–20

    Article  PubMed  Google Scholar 

  24. Yurekli VA, Akhan G, Kutluhan S, et al. The effect of sodium valproate on chronic daily headache and its subgroups. J Headache Pain 2008; 9(1): 37–41

    Article  PubMed  CAS  Google Scholar 

  25. Bartolini M, Silvestrini M, Taffi R, et al. Efficacy of topiramate and valproate in chronic migraine. Clin Neuropharmacol 2005; 28(6): 277–9

    Article  PubMed  CAS  Google Scholar 

  26. Schulman EA, Lake 3rd AE, Goadsby PJ, et al. Defining refractory migraine and refractory chronic migraine: proposed criteria from the Refractory Headache Special Interest Section of the American Headache Society. Headache 2008 Jun; 48(6): 778–82

    Article  PubMed  Google Scholar 

  27. Ghose K, Niven B. Prophylactic sodium valproate therapy in patients with drug-resistant migraine. Methods Find Exp Clin Pharmacol 1998; 20(4): 353–9

    Article  PubMed  CAS  Google Scholar 

  28. Erdemoglu AK, Ozbakir S. Valproic acid in prophylaxis of refractory migraine. Acta Neurol Scand 2000; 102(6): 354–8

    Article  PubMed  CAS  Google Scholar 

  29. Pascual J, Leira R, Láinez JM. Combined therapy for migraine prevention? Clinical experience with a beta-blocker plus sodium valproate in 52 resistant migraine patients. Cephalalgia 2003; 23(10): 961–2

    Article  PubMed  CAS  Google Scholar 

  30. Mansoureh T, Rahmat Jirde M, Nilavari K, et al. Cinnarizine in refractory migraine prophylaxis: efficacy and tolerability. A comparison with sodium valproate. J Headache Pain 2008; 9(2): 77–82

    Article  CAS  Google Scholar 

  31. Caruso JM, Brown WD, Exil G, et al. The efficacy of divalproex sodium in the prophylactic treatment of children with migraine. Headache 2000; 40(8): 672–6

    Article  PubMed  CAS  Google Scholar 

  32. Serdaroglu G, Erhan E, Tekgul H, et al. Sodium valproate prophylaxis in childhood migraine. Headache 2002; 42(8): 819–22

    Article  PubMed  Google Scholar 

  33. Ashrafi MR, Shabanian R, Zamani GR, et al. Sodium valproate versus propranolol in paediatric migraine prophylaxis. Eur J Paediatr Neurol 2005; 9(5): 333–8

    Article  PubMed  CAS  Google Scholar 

  34. Apostol G, Cady RK, Laforet GA, et al. Divalproex extended-release in adolescent migraine prophylaxis: results of a randomized, double-blind, placebo-controlled study. Headache 2008; 48(7): 1012–25

    Article  PubMed  Google Scholar 

  35. Storey JR, Calder CS, Hart DE, et al. Topiramate in migraine prevention: a double-blind, placebo-controlled study. Headache 2001; 41(10): 968–75

    Article  PubMed  CAS  Google Scholar 

  36. Mei D, Capuano A, Vollono C, et al. Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study. Neurol Sci 2004; 25(5): 245–50

    Article  PubMed  CAS  Google Scholar 

  37. Martínez HR, Londoño O, Cantú-Martínez L, et al. Topiramate as an adjunctive treatment in migraine prophylaxis. Headache 2003; 43(10): 1080–4

    Article  PubMed  Google Scholar 

  38. Edwards KR, Potter DL, Wu SC, et al. Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot, double-blind, placebo-controlled trials. CNS Spectr 2003; 8(6): 428–32

    PubMed  Google Scholar 

  39. Silberstein SD, Neto W, Schmitt J, et al. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol 2004; 61(4): 490–5

    Article  PubMed  Google Scholar 

  40. Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004; 291(8): 965–73

    Article  PubMed  CAS  Google Scholar 

  41. Diener HC, Tfelt-Hansen P, Dahlöf C, et al. Topiramate in migraine prophylaxis: results from a placebo-controlled trial with propranolol as an active control. J Neurol 2004; 251(8): 943–50

    Article  PubMed  CAS  Google Scholar 

  42. Silberstein SD, Hulihan J, Karim MR, et al. Efficacy and tolerability of topiramate 200mg/d in the prevention of migraine with/without aura in adults: a randomized, placebo-controlled, double-blind, 12-week pilot study. Clin Ther 2006; 28(7): 1002–11

    Article  PubMed  CAS  Google Scholar 

  43. Lee ST, Chu K, Park JE, et al. Paresthesia as a favorable predictor of migraine prophylaxis using topiramate. Eur J Neurol 2007; 14(6): 654–8

    Article  PubMed  Google Scholar 

  44. Rapoport A, Mauskop A, Diener HC, et al. Long-term migraine prevention with topiramate: open-label extension of pivotal trials. Headache 2006; 46(7): 1151–60

    Article  PubMed  Google Scholar 

  45. Limmroth V, Biondi D, Pfeil J, et al. Topiramate in patients with episodic migraine: reducing the risk for chronic forms of headache. Headache 2007; 47(1): 13–21

    Article  PubMed  Google Scholar 

  46. Headache Classification Committee of The International Headache Society. The international classification of headache disorders, 2nd edition. Cephalalgia 2004; 24Suppl. 1: 1–160

    Google Scholar 

  47. 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 Dec; 6(12): 1054–62

    Article  PubMed  CAS  Google Scholar 

  48. Gupta P, Singh S, Goyal V, et al. Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp study). Headache 2007 Mar; 47(3): 402–12

    PubMed  Google Scholar 

  49. Millán-Guerrero RO, Isais-Millán R, Barreto-Vizcaíno S, et al. Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study. Eur Neurol 2008; 59(5): 237–42

    Article  PubMed  Google Scholar 

  50. Dahlöf C, Loder E, Diamond M, et al. The impact of migraine prevention on daily activities: a longitudinal and responder analysis from three topiramate placebo-controlled clinical trials. Health Qual Life Outcomes 2007; 5: 56

    Article  PubMed  Google Scholar 

  51. Brandes JL, Kudrow DB, Rothrock JF, et al. Assessing the ability of topiramate to improve the daily activities of patients with migraine. Mayo Clin Proc 2006 Oct; 81(10): 1311–9

    Article  PubMed  CAS  Google Scholar 

  52. Lofland JH, Gagne JJ, Pizzi LT, et al. Impact of topiramate migraine prophylaxis on workplace productivity: results from two US randomized, double-blind, placebo-controlled, multicenter trials. J Occup Environ Med 2007; 49(3): 252–7

    Article  PubMed  Google Scholar 

  53. Silvestrini M, Bartolini M, Coccia M, et al. Topiramate in the treatment of chronic migraine. Cephalalgia 2003 Oct; 23(8): 820–4

    Article  PubMed  CAS  Google Scholar 

  54. Peres MF, Mercante JP, Tanuri FC, et al. Chronic migraine prevention with topiramate. J Headache Pain 2006 Sep; 7(4): 185–7

    Article  PubMed  CAS  Google Scholar 

  55. 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 Jul; 27(7): 814–23

    Article  PubMed  Google Scholar 

  56. Silberstein SD, Lipton RB, Dodick DW, et al. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache 2007 Feb; 47(2): 170–80

    Article  PubMed  Google Scholar 

  57. Dodick DW, Silberstein S, Saper J, et al. The impact of topiramate on health-related quality of life indicators in chronic migraine. Headache 2007 Nov–Dec; 47(10): 1398–408

    Article  PubMed  Google Scholar 

  58. Pascual J, Sánchez del Rio M, Mateos V, et al. Topiramate for patients with refractory migraine: an observational, multicenter study in Spain. Neurologia 2003 Sep; 18(7): 364–7

    PubMed  CAS  Google Scholar 

  59. Pascual J, Rivas MT, Leira R. Testing the combination beta-blocker plus topiramate in refractory migraine. Acta Neurol Scand 2007 Feb; 115(2): 81–3

    Article  PubMed  CAS  Google Scholar 

  60. Winner P, Gendolla A, Stayer C, et al. Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy and safety. Headache 2006 Nov–Dec; 46(10): 1503–10

    Article  PubMed  Google Scholar 

  61. Campistol J, Campos J, Casas C, et al. Topiramate in the prophylactic treatment of migraine in children. J Child Neurol 2005 Mar; 20(3): 251–3

    PubMed  Google Scholar 

  62. Hershey AD, Powers SW, Vockell AL, et al. Effectiveness of topiramate in the prevention of childhood headaches. Headache 2002 Sep; 42(8): 810–8

    Article  PubMed  Google Scholar 

  63. Winner P, Pearlman EM, Linder SL, et al. Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial. Headache 2005 Nov–Dec; 45(10): 1304–12

    Article  PubMed  Google Scholar 

  64. Lakshmi CV, Singhi P, Malhi P, et al. Topiramate in the prophylaxis of pediatric migraine: a double-blind placebo-controlled trial. J Child Neurol 2007 Jul; 22(7): 829–35

    Article  PubMed  CAS  Google Scholar 

  65. Lewis D, Paradiso E. A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study. Headache 2007 Nov–Dec; 47(10): 1409–17

    PubMed  Google Scholar 

  66. Vahedi K, Taupin P, Djomby R, et al. Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomized placebo-controlled trial. J Neurol 2002 Feb; 249(2): 206–11

    Article  PubMed  CAS  Google Scholar 

  67. Rompel H, Bauermeister PW. Aetiology of migraine and prevention with carbamazepine (Tegretol): results of a double-blind, cross-over study. S Afr Med J 1970; 44: 75–80

    PubMed  CAS  Google Scholar 

  68. Di Trapani G, Mei D, Marra C, et al. Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study. Clin Ther 2000 May–Jun; 151(3): 145–8

    Google Scholar 

  69. Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapentin in migraine prophylaxis. Headache 2001 Feb; 41(2): 119–28

    Article  PubMed  CAS  Google Scholar 

  70. Bigal ME, Krymchantowski AV, Rapoport AM. New developments in migraine prophylaxis. Expert Opin Pharmacother 2003; 4(4): 1–11

    Article  Google Scholar 

  71. Steiner TJ, Findley LJ, Yuen AW. Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia 1997 Apr; 17(2): 109–12

    Article  PubMed  CAS  Google Scholar 

  72. D’Andrea G, Granella F, Cadaldini M, et al. Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study. Cephalalgia 1999 Jan; 19(1): 64–6

    Article  PubMed  Google Scholar 

  73. Lampl C, Katsarava Z, Diener HC, et al. Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. J Neurol Neurosurg Psychiatry 2005 Dec; 76(12): 1730–2

    Article  PubMed  CAS  Google Scholar 

  74. Lampl C, Buzath A, Klinger D, et al. Lamotrigine in the prophylactic treatment of migraine aura: a pilot study. Cephalalgia 1999 Jan; 19(1): 58–63

    Article  PubMed  CAS  Google Scholar 

  75. Pascual J, Caminero AB, Mateos V, et al. Preventing disturbing migraine aura with lamotrigine: an open study. Headache 2004 Nov–Dec; 44(10): 1024–8

    Article  PubMed  Google Scholar 

  76. D’Andrea G, Nordera GP, Allais G. Treatment of aura: solving the puzzle. Neurol Sci 2006 May; 27Suppl. 2: S96–9

    Article  PubMed  Google Scholar 

  77. Brighina F, Palermo A, Aloisio A, et al. Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study. Clin Neuropharmacol 2006 Nov–Dec; 29(6): 338–42

    Article  PubMed  CAS  Google Scholar 

  78. Pakalnis A, Kring D, Meier L. Levetiracetam prophylaxis in pediatric migraine: an open-label study. Headache 2007 Mar; 47(3): 427–30

    Article  PubMed  Google Scholar 

  79. Silberstein S, Saper J, Berenson F, et al. Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study. Neurology 2008 Feb 12; 70(7): 548–55

    Article  PubMed  CAS  Google Scholar 

  80. Ghose K, Niven BE, Berry D. A double-blind crossover comparison of the effects of vigabatrin with placebo in the prevention of migraine headache. J Headache Pain 2002; 3: 79–85

    Article  CAS  Google Scholar 

  81. Drake Jr ME, Greathouse NI, Renner JB, et al. Open-label zonisamide for refractory migraine. Clin Neuropharmacol 2004 Nov–Dec; 27(6): 278–80

    Article  PubMed  CAS  Google Scholar 

  82. Ashkenazi A, Benlifer A, Korenblit J, et al. Zonisamide for migraine prophylaxis in refractory patients. Cephalalgia 2006 Oct; 26(10): 1199–202

    Article  PubMed  CAS  Google Scholar 

  83. Pakalnis A, Kring D. Zonisamide prophylaxis in refractory pediatric headache. Headache 2006 May; 46(5): 804–7

    Article  PubMed  Google Scholar 

  84. Mulleners WM, Chronicle EP. Anticonvulsants in migraine prophylaxis: a Cochrane review. Cephalalgia 2008; 28: 585–97

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

No funding or external support has been received for conducting this review and for the preparation of the manuscript.

The authors report the following possible conflicts of interest. Michail Vikelis is currently a part-time medical advisor for Janssen-Cilag, Hellas. In the past he has worked as a medical advisor for MerckSerono, Hellas. Alan Rapoport is on the speakers’ bureau for Endo, Merck, Pfizer and Forest. He is on the advisory board of MAP, Zogenix, NuPathe and Pfizer. In the past, he has been on the speakers bureau of Ortho-McNeil, GlaxoSmithKline, AstraZeneca and Valiant.

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Vikelis, M., Rapoport, A.M. Role of Antiepileptic Drugs as Preventive Agents for Migraine. CNS Drugs 24, 21–33 (2010). https://doi.org/10.2165/11310970-000000000-00000

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