Advertisement

Current Status of Antiepileptic Drugs as Preventive Migraine Therapy

  • Simy K. Parikh
  • Stephen D. SilbersteinEmail author
Headache (JR Couch, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Headache

Abstract

Background

Antiepileptic drugs (AEDs) are an important class of agents used in the treatment of migraine, a neurological disorder that imparts significant socioeconomic burden. It is important for neurologists to understand the rationale for AEDs in migraine-preventive treatment, as well as each agent’s efficacy and tolerability profile, in order to best determine clinical care.

Purpose of this review

This article specifically provides the following: (1) a review of the mechanism of action, efficacy, and tolerability of topiramate and divalproex sodium/sodium valproate, the most widely used AEDs for migraine prevention, (2) a discussion on emerging evidence regarding the efficacy of zonisamide and levetiracetam, and (3) comments on gabapentin, pregabalin, carbamazepine, oxcarbazepine, and lamotrigine, AEDs which have insufficient evidence for use in migraine prevention.

Recent findings

The potential role for new extended-release formulations of topiramate in migraine prevention is discussed.

Summary

There is substantial evidence supporting the use of AEDs in migraine prevention. Specific agents should be chosen based on their efficacy and tolerability profiles. Further studies are needed to determine the efficacy of the newer AEDs, zonisamide and levetiracetam, in migraine prevention and to clarify the role of gabapentinoids in headache management.

Keywords

Migraine Headache Preventive therapy Pharmacology Antiepileptic drugs Anticonvulsants 

Notes

Funding Information

The research was partially funded by The Groten Family Fund.

Compliance with Ethical Standards

Conflict of Interest

Stephen D. Silberstein reports personal fees from Alder Biopharmaceuticals, grants and personal fees from Allergan, grants and personal fees from Amgen, grants and personal fees from Avanir Pharmaceuticals Inc., personal fees from eNeura, non-financial support from Curelator, Inc., grants and personal fees from electroCore Medical, LLC, grants and personal fees from Dr. Reddy’s Laboratories, personal fees from Medscape, LLC, grants and personal fees from Teva Pharmaceuticals, grants and personal fees from Supernus Pharmaceuticals, Inc., grants and personal fees from Eli Lilly and Company, personal fees from Theranica, non-financial support from Trigemina, Inc., outside the submitted work. Simy Parikh declares that she has no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343–9 This article highlights the significant socioeconomic burden of migraine and the need for efficacious preventive therapy.Google Scholar
  2. 2.
    Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;386:743–800.Google Scholar
  3. 3.
    Stokes M, Becker WJ, Lipton RB, Sullivan SD, Wilcox TK, Wells L, 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(7):1058–77.Google Scholar
  4. 4.
    Linde M, Gustavsson A, Stovner LJ, Steiner TJ, Barré J, Katsarava Z, et al. The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol. 2012;19:703–11.PubMedGoogle Scholar
  5. 5.
    Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States data from the American migraine study II. Headache. 2001;41:646–57.Google Scholar
  6. 6.
    •• Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: Table 1. Neurology. 2012;78:1337–45 This article provides updated evidence-based recommendations based for AEDs in the preventive treatment of migraine headache.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Minen MT, Anglin C, Boubour A, Squires A, Herrmann L. Meta-synthesis on migraine management. Headache J Head Face Pain. 2018;58:22–44.Google Scholar
  8. 8.
    • • Bernstein C, Burstein R. Sensitization of the trigeminovascular pathway: perspective and implications to migraine pathophysiology. J Clin Neurol. 2012;8:89–99 This article provides a comprehensive assessment on the features of migraine pathophysiology.PubMedGoogle Scholar
  9. 9.
    White HS. Molecular pharmacology of topiramate: managing seizures and preventing migraine. Headache. 2005;45(Suppl 1):S48–56.PubMedGoogle Scholar
  10. 10.
    Waeber C, Moskowitz MA. Therapeutic implications of central and peripheral neurologic mechanisms in migraine. Neurology. 2003;61:S9–20.PubMedGoogle Scholar
  11. 11.
    Costa C, Tozzi A, Rainero I, Cupini LM, Calabresi P, Ayata C, et al. Cortical spreading depression as a target for anti-migraine agents. J Headache Pain. 2013;14:62.PubMedPubMedCentralGoogle Scholar
  12. 12.
    •• Linde M, Mulleners WM, Chronicle EP, McCrory DC. Antiepileptics other than gabapentin, pregabalin, topiramate, and valproate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013;(6):CD010608 This is a comprehensive assessment from controlled trials on the efficacy and tolerability of AEDs in migraine-preventive therapy.Google Scholar
  13. 13.
    •• Linde M, Mulleners WM, Chronicle EP, McCrory DC. Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013:1–50 This is a comprehensive assessment from controlled tmigraine-preventive therapy.Google Scholar
  14. 14.
    Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE. An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia. 2000;41(Suppl 1):S3–9.PubMedGoogle Scholar
  15. 15.
    • Shank RP, Maryanoff BE. Molecular pharmacodynamics, clinical therapeutics, and pharmacokinetics of topiramate. CNS Neurosci Ther. 2008;14:120–42 This is a comprehensive review of the molecular and pharmacological aspects of topiramate.Google Scholar
  16. 16.
    •• Silberstein SD. Topiramate in migraine prevention: a 2016 perspective. Headache J Head Face Pain. 2017;57:165–78 This article provides an updated, comprehensive review on the molecular targets, efficacy, and tolerability of topiramate.Google Scholar
  17. 17.
    Sigel E. Functional modulation of ligand-gated GABAA and NMDA receptor channels by phosphorylation. J Recept Signal Transduct Res. 1995;15:325–32.PubMedGoogle Scholar
  18. 18.
    Somjen GG. Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev. 2001;81:1065–96.PubMedGoogle Scholar
  19. 19.
    Zhang X, Velumian AA, Jones OT, Carlen PL. Modulation of high-voltage-activated calcium channels in dentate granule cells by topiramate. Epilepsia. 2000;41(Suppl 1):S52–60.PubMedGoogle Scholar
  20. 20.
    Akerman S, Goadsby PJ. Topiramate inhibits trigeminovascular activation: an intravital microscopy study. Br J Pharmacol. 2005;146:7–14.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Durham PL, Niemann C, Cady R. Repression of stimulated calcitonin gene-related peptide secretion by topiramate. Headache. 2006;46:1291–5.PubMedGoogle Scholar
  22. 22.
    White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia. 2000;41(Suppl 1):S17–20.PubMedGoogle Scholar
  23. 23.
    Herrero AI, Del Olmo N, González-Escalada JR, Solís JM. Two new actions of topiramate: inhibition of depolarizing GABA(A)-mediated responses and activation of a potassium conductance. Neuropharmacology. 2002;42:210–20.PubMedGoogle Scholar
  24. 24.
    Akerman S, Goadsby PJ. Topiramate inhibits cortical spreading depression in rat and cat: impact in migraine aura. Neuroreport. 2005;16:1383–7.PubMedGoogle Scholar
  25. 25.
    Akerman S, Holland PR, Goadsby PJ. Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade. Brain Res. 2008;1229:27–36.PubMedGoogle Scholar
  26. 26.
    Holland PR, Akerman S, Goadsby PJ. Cortical spreading depression-associated cerebral blood flow changes induced by mechanical stimulation are modulated by AMPA and GABA receptors. Cephalalgia. 2010;30:519–27.PubMedGoogle Scholar
  27. 27.
    Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006;59:652–61.Google Scholar
  28. 28.
    Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291:965.PubMedPubMedCentralGoogle Scholar
  29. 29.
    •• Silberstein S, Lipton R, Dodick D, Freitag F, Mathew N, Brandes J, et al. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measures. Headache. 2009;49:1153–62 This study provides data on the benefit of topiramate on clinically relevant secondary outcomes in migraine prevention.Google Scholar
  30. 30.
    Diener H-C, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ, et al. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27:814–23.Google Scholar
  31. 31.
    Diener H-C, Dodick D, Goadsby P, Bigal M, Bussone G, Silberstein S, et al. Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse. Cephalalgia. 2009;29:1021–7.PubMedGoogle Scholar
  32. 32.
    Dodick DW, Silberstein S, Saper J, Freitag FG, Cady RK, Rapoport AM, et al. The impact of topiramate on health-related quality of life indicators in chronic migraine. Headache. 2007;47:1398–408.PubMedGoogle Scholar
  33. 33.
    Lipton RB, Silberstein S, Dodick D, Cady R, Freitag F, Mathew N, et al. Topiramate intervention to prevent transformation of episodic migraine: the topiramate INTREPID study. Cephalalgia. 2011;31:18–30.PubMedGoogle Scholar
  34. 34.
    Ashtari F, Shaygannejad V, Akbari M. A double-blind, randomized trial of low-dose topiramate vs propranolol in migraine prophylaxis. Acta Neurol Scand. 2008;118:301–5.Google Scholar
  35. 35.
    Gupta P, Singh S, Goyal V, Shukla G, Behari M. Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp study). Headache. 2007;47:402–12.PubMedGoogle Scholar
  36. 36.
    Diener H-C, Tfelt-Hansen P, Dahlöf C, Láinez MJA, Sandrini G, Wang S-J, et al. Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control. J Neurol. 2004;251:943–50.PubMedGoogle Scholar
  37. 37.
    •• Silberstein SD. Topiramate in migraine prevention: evidence-based medicine from clinical trials. Neurol Sci. 2004;25:s244–5 This article reviews the evidence that proves the safety and efficacy of topiramate in migraine prevention.PubMedGoogle Scholar
  38. 38.
    •• Silberstein SD, Neto W, Schmitt J, Jacobs D. MIGR-001 Study Group. Topiramate in migraine prevention. Arch Neurol. 2004;61:490 This is a double-blinded, placebo-controlled study providing data on the efficacy and safety of topiramate as a migraine-preventive therapy.Google Scholar
  39. 39.
    Storey JR, Calder CS, Hart DE, Potter DL. Topiramate in migraine prevention: a double-blind, placebo-controlled study. Headache. 41(10):968–75.Google Scholar
  40. 40.
    Dodick DW, Freitag F, Banks J, Saper J, Xiang J, Rupnow M, et al. Topiramate versus amitriptyline in migraine prevention: a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority trial in adult Migraineurs. Clin Ther. 2009;31:542–59.PubMedGoogle Scholar
  41. 41.
    Keskinbora K, Aydinli I. A double-blind randomized controlled trial of topiramate and amitriptyline either alone or in combination for the prevention of migraine. Clin Neurol Neurosurg. 2008;110:979–84.PubMedGoogle Scholar
  42. 42.
    Shaygannejad V, Janghorbani M, Ghorbani A, Ashtary F, Zakizade N, Nasr V. Comparison of the effect of topiramate and sodium valporate in migraine prevention: a randomized blinded crossover study. Headache. 2006;46:642–8.PubMedGoogle Scholar
  43. 43.
    Adelman J, Freitag FG, Lainez M, Shi Y, Ascher S, Mao L, et al. Analysis of safety and tolerability data obtained from over 1,500 patients receiving topiramate for migraine prevention in controlled trials. Pain Med. 2008;9:175–85.PubMedGoogle Scholar
  44. 44.
    Luykx J, Mason M, Ferrari MD, Carpay J. Are migraineurs at increased risk of adverse drug responses? A meta-analytic comparison of topiramate-related adverse drug reactions in epilepsy and migraine. Clin Pharmacol Ther. 2009;85:283–8.PubMedGoogle Scholar
  45. 45.
    Tsai M-J, Chen Y-T, Ou S-M, Shin C-J, Peng K-P, Tang C-H, et al. Increased risk of urinary calculi in patients with migraine: a nationwide cohort study. Cephalalgia. 2015;35:652–61.PubMedGoogle Scholar
  46. 46.
    Brittain ST, Wheless JW. Pharmacokinetic simulations of topiramate plasma concentrations following dosing irregularities with extended-release vs. immediate-release formulations. Epilepsy Behav. 2015;52:31–6.PubMedGoogle Scholar
  47. 47.
    Mulleners WM, Whitmarsh TE, Steiner TJ. Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better. Cephalalgia. 1998;18:52–6.PubMedGoogle Scholar
  48. 48.
    Pascual J, El Berdei Y, Gómez-Sánchez JC. How many migraine patients need prolonged (>1 year) preventive treatment? Experience with topiramate. J Headache Pain. 2007;8:90–3.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Diener H-C, Agosti R, Allais G, Bergmans P, Bussone G, Davies B, et al. Cessation versus continuation of 6-month migraine preventive therapy with topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2007;6:1054–62.PubMedGoogle Scholar
  50. 50.
    Rapoport A, Mauskop A, Diener H-C, Schwalen S, Pfeil J. Long-term migraine prevention with topiramate: open-label extension of pivotal trials. Headache. 2006;46:1151–60.PubMedGoogle Scholar
  51. 51.
    Löscher W. The discovery of valproate. In: Löscher W, editor. Valproate Milestones in Drug Therapy. Birkhäuser, Basel; 1999.Google Scholar
  52. 52.
    •• Silberstein SD. Divalproex sodium in headache: literature review and clinical guidelines. Headache J Head Face Pain. 1996;36:547–55 This is a comprehensive review on the molecular targets and efficacy of divalproex sodium for migraine prevention.Google Scholar
  53. 53.
    Cutrer F, Limmroth V, Moskowitz M. Possible mechanisms of valproate in migraine prophylaxis. Cephalalgia. 1997;17:93–100.PubMedGoogle Scholar
  54. 54.
    Hering R, Kuritzky A. Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia. SAGE PublicationsSage UK: London, England. 1992;12:81–4.Google Scholar
  55. 55.
    Jensen R, Brinck T, Olesen J, Goldstein J, Saper J, Silberstein S, et al. Sodium valproate has a prophylactic effect in migraine without aura: a triple-blind, placebo-controlled crossover study. Neurology. 1994;44:647–51.Google Scholar
  56. 56.
    Klapper J. Divalproex Sodium in Migraine Prophylaxis. Cephalalgia. 1997;17:103–8.PubMedGoogle Scholar
  57. 57.
    Freitag FG, Collins SD, Carlson HA, Goldstein J, Saper J, Silberstein S, et al. A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis. Neurology. 2002;58:1652–9.PubMedGoogle Scholar
  58. 58.
    Kaniecki RG. A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Arch Neurol. 1997;54:1141–5.PubMedGoogle Scholar
  59. 59.
    Afshari D, Rafizadeh S, Rezaei M. A comparative study of the effects of low-dose topiramate versus sodium valproate in migraine prophylaxis. Int J Neurosci. 2012;122:60–8.PubMedGoogle Scholar
  60. 60.
    •• 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;(6):CD010611 This is a comprehensive assessment from controlled trials on the efficacy and tolerability of valporate in migraine-preventive therapy.Google Scholar
  61. 61.
    •• Silberstein SD, Collins SD. Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term safety of Depakote in headache prophylaxis study group. Headache. 1999;39:633–43 This is an open-label study providing evidence for the long-term safety of divalproex sodium for migraine prevention.Google Scholar
  62. 62.
    Amrutkar DV, Ploug KB, Olesen J, Jansen-Olesen I. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system. Neuroscience. 2011;172:510–7.PubMedGoogle Scholar
  63. 63.
    Ashkenazi A, Benlifer A, Korenblit J, Silberstein S. Zonisamide for migraine prophylaxis in refractory patients. Cephalalgia. 2006;26:1199–202.PubMedGoogle Scholar
  64. 64.
    Bermejo PE, Dorado R. Zonisamide for migraine prophylaxis in patients refractory to topiramate. Clin Neuropharmacol. 2009;32(2):103–6.PubMedGoogle Scholar
  65. 65.
    Mohammadianinejad SE, Abbasi V, Sajedi SA, Majdinasab N, Abdollahi F, Hajmanouchehri R, et al. Zonisamide versus topiramate in migraine prophylaxis. Clin Neuropharmacol. 2011;34:174–7.PubMedGoogle Scholar
  66. 66.
    Villani V, Ciuffoli A, Prosperini L, Sette G. Zonisamide for migraine prophylaxis in topiramate-intolerant patients: an observational study. Headache J Head Face Pain. 2011;51:287–91.Google Scholar
  67. 67.
    Baulac M, Patten A, Giorgi L. Long-term safety and efficacy of zonisamide versus carbamazepine monotherapy for treatment of partial seizures in adults with newly diagnosed epilepsy: results of a phase III, randomized, double-blind study. Epilepsia. 2014;55:1534–43.PubMedGoogle Scholar
  68. 68.
    Rapoport AM, Sheftell FD, Tepper SJ, Bigal ME. Levetiracetam in the preventive treatment of transformed migraine: a prospective, open-label, pilot study. Curr Ther Res. 2005;66:212–21.PubMedGoogle Scholar
  69. 69.
    Verma A, Srivastava D, Kumar A, Singh V. Levetiracetam in migraine prophylaxis. Clin Neuropharmacol. 2013;36:193–7.PubMedGoogle Scholar
  70. 70.
    Sadeghian H, Motiei-Langroudi R. Comparison of Levetiracetam and sodium valproate in migraine prophylaxis: a randomized placebo-controlled study. Ann Indian Acad Neurol. 2015;18:45–8.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B. Levetiracetam in the prophylaxis of migraine with aura. Clin Neuropharmacol. 2006;29:338–42.PubMedGoogle Scholar
  72. 72.
    Watkins AK, Gee ME, Brown JN. Efficacy and safety of levetiracetam for migraine prophylaxis: a systematic review. J Clin Pharm Ther. 2018;43:467–75.PubMedGoogle Scholar
  73. 73.
    Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004;101:9861–6.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Richter F, Ebersberger A, Schaible H-G. Blockade of voltage-gated calcium channels in rat inhibits repetitive cortical spreading depression. Neurosci Lett. 2002;334:123–6.PubMedGoogle Scholar
  75. 75.
    Beran RG, Spira PJ. Levetiracetam in chronic daily headache: a double-blind, randomised placebo-controlled study. (The Australian KEPPRA Headache Trial [AUS-KHT]). Cephalalgia. 2011;31:530–6.PubMedGoogle Scholar
  76. 76.
    de Tommaso M, Guido M, Sardaro M, Serpino C, Vecchio E, De Stefano G, et al. Effects of topiramate and levetiracetam vs placebo on habituation of contingent negative variation in migraine patients. Neurosci Lett. 2008;442:81–5.PubMedGoogle Scholar
  77. 77.
    Bootsma HPR, Ricker L, Diepman L, Gehring J, Hulsman J, Lambrechts D, et al. Long-term effects of levetiracetam and topiramate in clinical practice: a head-to-head comparison. Seizure. 2008;17:19–26.PubMedGoogle Scholar
  78. 78.
    Perloff MD, Berlin RK, Gillette M, Petersile MJ, Kurowski D. Gabapentin in headache disorders: what is the evidence? Pain Med. 2016;17:162–71.PubMedGoogle Scholar
  79. 79.
    Zhang Y, Shao G, Zhang W, Li S, Niu J, Hu D, et al. Gabapentin inhibits central sensitization during migraine. Neural Regen Res. 2013;8:3003–12.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Hoffmann U, Dileköz E, Kudo C, Ayata C. Gabapentin suppresses cortical spreading depression susceptibility. J Cereb Blood Flow Metab. 2010;30:1588–92.PubMedPubMedCentralGoogle Scholar
  81. 81.
    •• Silberstein S, Goode-Sellers S, Twomey C, Saiers J, Ascher J. Randomized, double-blind, placebo-controlled, phase II trial of gabapentin enacarbil for migraine prophylaxis. Cephalalgia. 2013;33:101–11 This is a double-blinded, placebo-controlled study providing evidence that gabapentin does not significantly differ from placebo when used for migraine-preventive therapy.Google Scholar
  82. 82.
    Mathew NT, Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, et al. Efficacy of gabapentin in migraine prophylaxis. Headache. 2001;41:119–28.PubMedGoogle Scholar
  83. 83.
    Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs. 2017;77:403–26.PubMedGoogle Scholar
  84. 84.
    Hesami O, Shams MR, Ayazkhoo L, Assarzadegan F, Safarpour Lima B, Delavar Kasmaei H, et al. Comparison of pregabalin and sodium valproate in migraine prophylaxis: a randomized double-blinded study. Iran J Pharm Res IJPR. 2018;17:783–9.PubMedGoogle Scholar
  85. 85.
    Steiner TJ, Findley LJ, Yuen AW. Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia. 1997;17:109–12.PubMedGoogle Scholar
  86. 86.
    Bogdanov VB, Multon S, Chauvel V, Bogdanova OV, Prodanov D, Makarchuk MY, et al. Migraine preventive drugs differentially affect cortical spreading depression in rat. Neurobiol Dis. 2011;41:430–5.PubMedGoogle Scholar
  87. 87.
    Dailey JW, Reith ME, Steidley KR, Milbrandt JC, Jobe PC. Carbamazepine-induced release of serotonin from rat hippocampus in vitro. Epilepsia. 1998;39:1054–63.PubMedGoogle Scholar
  88. 88.
    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.PubMedGoogle Scholar
  89. 89.
    •• Silberstein S, Saper J, Berenson F, Somogyi M, McCague K, D’Souza J. Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study. Neurology. 2008;70:548–55 This is a double-blinded, placebo-controlled study providing evidence that oxcarbazepine does not significantly differ from placebo when used for migraine-preventive therapy.PubMedGoogle Scholar
  90. 90.
    Meadow R. Anticonvulsants in Pregnancy. Arch Dis Child. 1991;66:62–5.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Weston J, Bromley R, Jackson CF, Adab N, Clayton-Smith J, Greenhalgh J, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev. 2016;11:CD010224.PubMedGoogle Scholar
  92. 92.
    Veiby G, Engelsen BA, Gilhus NE. Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding. JAMA Neurol. 2013;70:1367.PubMedGoogle Scholar
  93. 93.
    Veroniki AA, Cogo E, Rios P, Straus SE, Finkelstein Y, Kealey R, et al. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes. BMC Med. BioMed Central. 2017;15:95.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Jefferson Headache CenterThomas Jefferson UniversityPhiladelphiaUSA

Personalised recommendations