Skip to main content

Advertisement

SpringerLink
Log in

Antiepileptic drug therapy in migraine headache

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

  • Severe migraine affects more than 28 million Americans. It is associated with episodic as well as long-term disability and suffering, yet it is underdiagnosed and undertreated.

  • Acute treatments have advanced considerably, ignited by sumatriptan and the subsequent triptans; unfortunately migraine prevention has lagged far behind.

  • There are no great migraine preventives! No migraine preventive agent studied in good randomized, double blind, placebo-controlled trials proved to be 50% better than placebo.

  • Migraine trials typically focus on episodic migraine, a milder, gentler type of migraine that is selected for low frequency, lack of daily headaches, no preventive need, and previous failure to no more than a few preventive agents. These features are not typical of the usual migraine patient seen in most neurologic practices, thus the results of clinical trials may not carryover to real world situations.

  • Treatment of frequent, chronic, or pervasive migraine is inadequate, and never has been studied in randomized controlled trials. Traditional migraine preventives, eg, beta-blockers, calcium channel blockers, and tricyclic antidepressants, are often ineffective in difficult or complicated populations.

  • The antiepileptic drugs represent a category of pharmaceutics that target the neuronal instability and central hyperexcitability of migraine, and, through these actions, may be more effective than traditional preventives.

  • Episodic migraine attacks are associated with peripheral and central sensitization; however, if attacks are frequent, severe, or long lasting, this sensitization may increase the risk of developing daily headaches.

  • If antiepileptic drugs have an effect on central sensitization, perhaps mediated via glutamate inhibition or gamma-aminobutyric acid potentiation, it is appropriate to use these agents early in migraine treatment, particularly in the highly comorbid patient, possibly in conjunction with agents that antagonize the 5HT2 receptor.

  • This report reviews the best currently available evidence on antiepileptic drugs in the prevention of episodic migraine, and tabulates potential drug-drug and cytochrome P450 interactions. All antiepileptic drugs presented are effective in migraine prevention. However, deciding on the best agent for each individual patient will require recognizing comorbidity and assessing antiepileptic drug pharmacodynamics, tolerability, and safety.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Goadsby PJ, Lipton RB, Ferrari MD: Migraine: current understanding and treatment. N Engl J Med 2002, 346:257–270. This is a great overview of migraine and its treatment with acute and preventive agents.

    Article  PubMed  CAS  Google Scholar 

  2. Aurora SK, Ahmad BK, Welch KMA, et al.: Transcranial magnetic stimulation confirms hyperexcitability of occipital cortex in migraine. Neurology 1998, 50:1111–1114.

    PubMed  CAS  Google Scholar 

  3. Palmer JE, Chronicle EP, Rolan P, Mulleners WM: Cortical hyperexcitability is cortical under-inhibition: evidence from a novel functional test of migraine patients. Cephalalgia 2000, 20:525–532. Using a technique of metacontrast visual masking, the evidence presented suggests under-inhibition of inhibitory systems as an explanation of cortical hyperexcitability.

    Article  PubMed  CAS  Google Scholar 

  4. Alam Z, Coombes N, Waring RH, et al.: Plasma levels of neuroexcitatory amino acids in patients with migraine and tension headache. J Neurol Sci 1998, 156:102–106.

    Article  PubMed  CAS  Google Scholar 

  5. Storer RJ, Akerman S, Goadsby PJ: GABA receptors modulate trigeminovascular nociceptive neurotransmission in the trigeminocervical complex. B J Pharm 2001, 134:896–904.

    Article  CAS  Google Scholar 

  6. Chugani DC, Niimura K, Chaturvedi S, et al.: Increased brain serotonin synthesis in migraine. Neurology 1999, 53:1473–1479.

    PubMed  CAS  Google Scholar 

  7. International Headache Society Clinical Trials Subcommittee: Guidelines for controlled trials of drugs in migraine: second edition. Cephalalgia 2000, 20:765–786.

    Article  Google Scholar 

  8. Holloway RG, Dick AW: Clinical trial end points: on the road to nowhere? Neurology 2002, 58:679–686. This article has some interesting insights on clinical trial endpoints as they apply to surrogate outcome measures, particularly since surrogates are substitutes for a clinically meaningful endpoint. Although, it may not be known what migraine patients want from acute therapies, there is not much insight regarding preventives.

    PubMed  Google Scholar 

  9. Ramadan NM, Schultz LL, Gilkey SJ: Migraine prophylactic drugs: proof of efficacy, utilization and cost. Cephalalgia 1997, 17:73–80. This study represents a timely review of migraine prophylactic trials, lack of scientific rigor and overall poor efficacy.

    Article  PubMed  CAS  Google Scholar 

  10. Cutrer FM, Limmroth V, Moskowitz MA: Possible mechanisms of valproate in migraine prophylaxis. Cephalalgia 1997, 17:93–100.

    Article  PubMed  CAS  Google Scholar 

  11. Leppik IE: Issues in the treatment of epilepsy. Epilepsia 2001, 42(suppl):1–6. A historically relevant overview of side effects, metabolism, pharmacokinetics, and pharmacodynamics of the AEDs.

    PubMed  Google Scholar 

  12. Rho JM, Sankar R: The pharmacologic basis of antiepileptic drug action. Epilepsia 1999, 11:1471–1483. This article presents a wonderful review of the multiple known mechanisms of action responsible for antiepileptic efficacy for most of the currently available AEDs.

    Article  Google Scholar 

  13. Goadsby PJ: How do the currently used prophylactic agents work in migraine? Cephalalgia 1997, 17:85–92. This article serves as a good starting point to understand the mechanisms of action of various migraine preventives.

    Article  PubMed  CAS  Google Scholar 

  14. Cutrer FM: Antiepileptic drugs; how they work in migraine. Headache 2001, 41(suppl):3–10. This represents a particularly good review of AED mechanisms of action that might help explain migraine efficacy.

    Article  Google Scholar 

  15. May A, Goadsby PJ: Pharmacological opportunities and pitfalls in the therapy of migraine. Curr Opin Neurol 2001, 14:341–345.

    Article  PubMed  CAS  Google Scholar 

  16. Faught E: Pharmacokinetic considerations in prescribing antiepileptic drugs. Epilepsia 2001, 42(suppl):19–23. Understanding the pharmacokinetics and pharamacodynamics of AEDs will take on huge importance as we use these agents more frequently off-label. This article helps guide in this particular arena.

    PubMed  Google Scholar 

  17. Michalets EL: Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998, 18:84–112. Drug interactions and cytochrome P 450 isoenzymes are detailed in a straightforward and thorough fashion. Particular attention is paid to the 3A4 isoenzyme since many of the AEDs are either substrates or inhibit or induce it.

    PubMed  CAS  Google Scholar 

  18. Physicians’ Desk Reference, edn 56. Montvale, NJ: Medical Economics Company, Inc.; 2002.

  19. Rompel H, Bauermeister PW: Aetiology of migraine and prevention with carbamazepine: results of a doubleblind, cross-over study. S Afr Med J 1970, 24:75–80.

    Google Scholar 

  20. Hering R, Kuritzky A: Sodium valproate in the prophylactic treatment of migraine: a double-blind study versus placebo. Cephalalgia 1992, 12:81–84.

    Article  PubMed  CAS  Google Scholar 

  21. Jensen R, Brinck T, Olesen J: Sodium valproate has a prophylactic effect in migraine without aura: a tripleblind, placebo-controlled crossover study. Neurology 1994, 44:647–651.

    PubMed  CAS  Google Scholar 

  22. Mathew NT, Saper JR, Silberstein SD, et al.: Migraine prophylaxis with divalproex. Arch Neurol 1995, 52:281–286.

    PubMed  CAS  Google Scholar 

  23. Klapper J: Divalproex sodium in migraine prophylaxis: a dose-controlled study. Cephalalgia 1997, 17:103–108.

    Article  PubMed  CAS  Google Scholar 

  24. Kaniecki RG: A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura. Arch Neurol 1997, 54:1141–1145.

    PubMed  CAS  Google Scholar 

  25. Di Trapani G, Mei D, Marra C, et al.: Gabapentin in the prophylaxis of migraine: a double-blind randomized placebo-controlled study. Clin Ter 2000, 151:145–148.

    PubMed  Google Scholar 

  26. Mathew NT, Magnus-Miller L, Saper J, et al.: Migraine prophylaxis with gabapentin. Headache 1999, 39:367.

    Google Scholar 

  27. Mathew NT, Rapoport A, Saper J, et al.: Efficacy of gabapentin in migraine prophylaxis. Headache 2001, 41:119–128.

    Article  PubMed  CAS  Google Scholar 

  28. Steiner TJ, Findley LJ, Yuen AWC: Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Cephalalgia 1997, 17:109–112.

    Article  PubMed  CAS  Google Scholar 

  29. Lampl C, Buzath A, Klinger D, Neumann K: Lamotrigine in the prophylactic treatment of migraine aura—a pilot study. Cephalalgia 1999, 19:58–63.

    Article  PubMed  CAS  Google Scholar 

  30. D’Andrea G, Granella F, Cadaldini M, Manzoni GC: Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study. Cephalalgia 1999, 19:64–66.

    Article  PubMed  CAS  Google Scholar 

  31. Edwards KR, Glantz MJ, Shea P, et al.: A double-blind, randomized trial of topiramate versus placebo in the prophylactic treatment of migraine headache with and without aura. Presented at the 1999 Meeting of the American Pain Society; Fort Lauderdale, FL. October 21–24, 1999;

  32. Edwards KR, Glantz MJ, Norton JA, Cross N: Prophylactic treatment of episodic migraine with topiramate: a double-blind, placebo-controlled trial in 30 patients. Cephalalgia 2000, 20:316.

    Google Scholar 

  33. Storey JR, Calder CS, Hart DE, Potter DL: Topiramate in migraine prevention: a double blind, placebo-controlled study. Headache 2001, 41:968–975.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ryan Wheeler Headache Treatment Center, 20601 Old Cutler Road, 33189, Miami, FL, USA

    Steve D. Wheeler MD

Authors
  1. Steve D. Wheeler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wheeler, S.D. Antiepileptic drug therapy in migraine headache. Curr Treat Options Neurol 4, 383–394 (2002). https://doi.org/10.1007/s11940-002-0049-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-002-0049-6

Keywords

Search

Navigation