Current Treatment Options in Neurology

, Volume 12, Issue 4, pp 287–299

New Antiepileptic Drugs: Lacosamide, Rufinamide, and Vigabatrin

Epilepsy

Opinion statement

The treatment of epilepsy is complicated by the multiple seizure types and epilepsy syndromes needing therapy. In addition, seizures in up to 30% of epilepsy patients are resistant to available medications. The three newest antiepileptic medications (lacosamide, rufinamide, and vigabatrin) all putatively have novel mechanisms of action, which might increase the chance of treatment success in patients failing previous antiepilepsy drug trials and the chance of successful synergy with currently available medications. In our experience, all three drugs generally are well tolerated, although the risk for serious long-term complications with vigabatrin presents special challenges and precautions. Lacosamide is approved for the adjunctive therapy of complex partial seizures in adults and also is available in an intravenous formulation. Rufinamide is a new treatment option for seizures associated with Lennox-Gastaut syndrome, and although it is not FDA approved for partial seizures, it has shown efficacy for that indication as well. Vigabatrin has been approved in adults for drug-resistant complex partial seizures and in infants as a treatment option for infantile spasms.

References and Recommended Reading

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

  1. 1.
    Hauser WA, Annegers JF, Kurland LT: Prevalence of epilepsy in Rochester, Minnesota: 1940–1980. Epilepsia 1991, 32:429–445.CrossRefPubMedGoogle Scholar
  2. 2.
    Ngugi AK, Bottomley C, Kleinschmidt I, et al.: Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 2010 Jan 7 (Epub ahead of print).Google Scholar
  3. 3.••
    Kwan P, Arzimanoglou A, Berg AT, et al.: Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2009 Nov 3 (Epub ahead of print). This recently published ILAE consensus statement on the definition of drug-resistant epilepsy provides a practical construct that may serve as a springboard for future increased consistency in the evaluation of AEDs in clinical trials.Google Scholar
  4. 4.
    Hesdorffer DC, Logroscino G, Cascino G, et al.: Incidence of status epilepticus in Rochester, Minnesota, 1965–1984. Neurology 1998, 50:735–741.PubMedGoogle Scholar
  5. 5.
    Brodie MJ, Rosenfeld WE, Vazquez B, et al.: Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial. Epilepsia 50:1899–1909.Google Scholar
  6. 6.
    Glauser T, Kluger G, Sachdeo R, et al.: Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008, 70:1950–1958.CrossRefPubMedGoogle Scholar
  7. 7.
    Ben-Menachem E, Biton V, Jatuzis D, et al.: Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007, 48(7):1308–1317.CrossRefPubMedGoogle Scholar
  8. 8.
    French JA, Mosier M, Walker S, et al.: A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Vigabatrin Protocol 024 Investigative Cohort. Neurology 1996, 46:54–61.PubMedGoogle Scholar
  9. 9.
    Dean C, Mosier M, Penry K: Dose-response study of vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures. Epilepsia 1999, 40:74–82.CrossRefPubMedGoogle Scholar
  10. 10.
    Chiron C, Dumas C, Jambaque I, et al.: Randomised trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis. Epilepsy Res 1997, 26:389–395.CrossRefPubMedGoogle Scholar
  11. 11.
    Appleton RE, Peters ACB, Memford JP, Shaw DE: Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia 1999, 40:1627–1633.CrossRefPubMedGoogle Scholar
  12. 12.
    Patorno E, Bohn RL, Wahl PM, et al.: Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death. JAMA 2010, 303(14):1401–1409.CrossRefPubMedGoogle Scholar
  13. 13.
    US Food and Drug Administration: Statistical review and evaluation: antiepileptic drugs and suicidality (May 23, 2008). Available at http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-00-index.html. Accessed April 2010.
  14. 14.
    Ben-Menachem E, Biton V, Jatuzis D, et al.: Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007, 48(7):1308–1317.CrossRefPubMedGoogle Scholar
  15. 15.
    Vimpat [prescribing information]. Smyrna, GA: UCB; 2009.Google Scholar
  16. 16.
    Cawello W, Nickel B, Eggert-Formella A: No pharmacokinetic interaction between lacosamide and carbamazepine in healthy volunteers. J Clin Pharmacol 2010, 50(4):459–471.CrossRefPubMedGoogle Scholar
  17. 17.
    Bialer M, Johannessen SI, Levy RH, et al.: Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res 2009, 83:1–43.CrossRefPubMedGoogle Scholar
  18. 18.
    Beyreuther BK, Freitag J, Heers C, et al.: Lacosamide: a review of preclinical properties. CNS Drug Rev 2007, 13:21–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Krauss G, Ben-Menachem E, Mameniskiene R, et al.: Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures. Epilepsia 2009 Dec 22 (Epub ahead of print).Google Scholar
  20. 20.
    Perucca E: What is the promise of new antiepileptic drugs in status epilepticus? Focus on brivaracetam, carisbamate, lacosamide, NS-1209 and topiramate. Epilepsia 2009, 50(Suppl 12):49–50.CrossRefPubMedGoogle Scholar
  21. 21.
    Kellinghaus C, Berning S, Besselmann M: Intravenous lacosamide as successful treatment for nonconvulsive status epilepticus after failure of first-line therapy. Epilepsy Behav 2009, 14:429–431.CrossRefPubMedGoogle Scholar
  22. 22.
    Stöhr T, Kupferberg HJ, Stables JP, et al.: Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res 2007, 74:147–154.CrossRefPubMedGoogle Scholar
  23. 23.
    Wymer JP, Simpson J, Sen D, et al.: on behalf of the Lacosamide SP742 Study Group: Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens. Clin J Pain 2009, 25:376–385.CrossRefPubMedGoogle Scholar
  24. 24.
    Shaibani A, Fares S, Selam JL, et al.: Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. J Pain 2009, 10(8):818–828.CrossRefPubMedGoogle Scholar
  25. 25.
    Red Book, Pharmacy’s Fundamental Reference. Montvale, NJ: Thomson Healthcare; 2009:269.Google Scholar
  26. 26.
    Bolin K, Berggren F, Forsgren L: Lacosamide as treatment of epileptic seizures-cost utility results for Sweden. Acta Neurol Scand 2010 Mar 1 (Epub ahead of print).Google Scholar
  27. 27.
    Wilby J, Kainth A, Hawkins N, et al.: Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation. Health Technol Assess 2005, 9(15):1–157, iii–iv.Google Scholar
  28. 28.
    Wheless JW, Conry J, Krauss G, et al.: 2009 Safety and tolerability of rufinamide in children with epilepsy: a pooled analysis of 7 clinical studies. J Child Neurol 2009, 24(12):1520–1525.CrossRefPubMedGoogle Scholar
  29. 29.
    Perucca E, Cloyd J, Critchley D, Fuseau E: Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia 2008, 49(7):1123–1141.CrossRefPubMedGoogle Scholar
  30. 30.
    Micromedex Healthcare Series [database online]. Greenwood Village, CO: Thomson Reuters (Healthcare) Inc.; updated periodically.Google Scholar
  31. 31.
    Benedict A, Verdian L, Maclaine G: The cost effectiveness of rufinamide in the treatment of Lennox-Gastaut syndrome in the UK. Pharmacoeconomics 2010, 28(3):185–199.CrossRefPubMedGoogle Scholar
  32. 32.••
    Willmore LJ, Abelson MB, Ben-Menachem E, et al.: Vigabatrin: 2008 update. Epilepsia 2009, 50:163–173.CrossRefPubMedGoogle Scholar
  33. 33.
    Schechter PJ, Hanke NFJ, Grove J, et al.: Biochemical and clinical effects of gamma-vinyl GABA in patients with epilepsy. Neurology 1984, 34:182–186.PubMedGoogle Scholar
  34. 34.
    Rimmer EM, Richens A: Interaction between vigabatrin and phenytoin. Br J Clin Pharmacol 1989, 27:27S–33S.PubMedGoogle Scholar
  35. 35.
    Gram L, Klosterskov P, Dam M: Gamma-vinyl GABA: a double-blind placebo-controlled trial in partial epilepsy. Ann Neurol 1985, 17:262–266.CrossRefPubMedGoogle Scholar
  36. 36.
    Loiseau P, Hardenberg JP, Pestre M, et al.: Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy. Epilepsia 1986, 27:115–120.CrossRefPubMedGoogle Scholar
  37. 37.
    Tartara A, Manni R, Galimberti CA, et al.: Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study. Epilepsia 1986, 27:717–723.CrossRefPubMedGoogle Scholar
  38. 38.
    Tassinari CA, Michelucci R, Ambrosetto G, et al.: Double-blind study of vigabatrin in the treatment of drug-resistant epilepsy. Arch Neurol 1987, 44:907–910.PubMedGoogle Scholar
  39. 39.
    French JA, Mosier M, Walker S, et al.: A double-blind, placebo-controlled study of vigabatrin three g/day in patients with uncontrolled complex partial seizures. Neurology 1996, 46:54–61.PubMedGoogle Scholar
  40. 40.
    Dean C, Mosier M, Penry K: Dose-response study of vigabatrin as add-on therapy in patients with uncontrolled complex partial seizures. Epilepsia 1999, 40:74–82.CrossRefPubMedGoogle Scholar
  41. 41.
    Bruni J, Guberman A, Vachon L: Desforges C; the Canadian Vigabatrin Study Group: Vigabatrin as add-on therapy for adult complex partial seizures: multicenter single-blind study with long-term follow-up. Seizure 2000, 9:224–232.CrossRefPubMedGoogle Scholar
  42. 42.
    Luna D, Dulac O, Pajot N, et al.: Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study. Epilepsia 1989, 30:430–437.CrossRefPubMedGoogle Scholar
  43. 43.
    Livingston JH, Beaumont D, Arzimanoglou A, et al.: Vigabatrin in the treatment of epilepsy in children. Br J Clin Pharmacol 1989, 27:109S–112S.PubMedGoogle Scholar
  44. 44.
    Appleton RE, Peters ACB, Memford JP, Shaw DE: Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms. Epilepsia 1999, 40:1627–1633.CrossRefPubMedGoogle Scholar
  45. 45.
    Siemes H, Brandl U, Spohr H-L, et al.: Long-term follow-up study of vigabatrin in pretreated children with West syndrome. Seizure 1998, 7:293–297.CrossRefPubMedGoogle Scholar
  46. 46.
    Chiron C, Dulac O, Luna D, et al.: Vigabatrin in infantile spasms [letter]. Lancet 1990, 335:363–364.CrossRefPubMedGoogle Scholar
  47. 47.
    Curatolo P, Verdecchia M, Bombardieri R: Vigabatrin for tuberous sclerosis complex. Brain Dev 2001, 23:649–653.CrossRefPubMedGoogle Scholar
  48. 48.
    Lux AL, Edwards SW, Hancock E, et al.: The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet 2004, 364:1773–1778.CrossRefPubMedGoogle Scholar
  49. 49.•
    Krauss GL: Evaluating risks for vigabatrin treatment. Epilepsy Curr 2009, 9:125–129CrossRefPubMedGoogle Scholar
  50. 50.
    Jedrzejczak J, Dlawichowska E, Owczarek K, et al.: Effect of vigabatrin addition on carbamazepine blood serum levels in patients with epilepsy. Epilepsy Res 2000, 39:115–120.CrossRefPubMedGoogle Scholar
  51. 51.
    Sanchez-Alcaraz A, Quintana M, Lopez E, et al.: Effect of vigabatrin on the pharmacokinetics of carbamazepine. J Clin Pharm Ther 2002, 27:427–430.CrossRefPubMedGoogle Scholar
  52. 52.
    Grant SM, Heel RC: Vigabatrin: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs 1991, 41:889–926.CrossRefPubMedGoogle Scholar
  53. 53.
    Kalviainen R, Nousiainen I, Mantyjarvi M, et al.: Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field defects. Neurology 1999, 53:922–926.PubMedGoogle Scholar
  54. 54.
    Wild JM, Ahn HS, Baulac M, et al.: Vigabatrin and epilepsy: lessons learned. Epilepsia 2007, 48:1318–1327.CrossRefPubMedGoogle Scholar
  55. 55.
    Hardus P, Verduin WM, Postma G, et al.: Long term changes in the visual fields of patients with temporal lobe epilepsy using vigabatrin. Br J Ophthalmol 2000, 84:788–790.CrossRefPubMedGoogle Scholar
  56. 56.
    Harding GF, Wild JM, Robertson KA, et al.: Separating the retinal electrophysiologic effects of vigabatrin. Neurology 2000, 55:347–352.PubMedGoogle Scholar
  57. 57.
    Gaily E, Jonsson H, Lappi M: Visual fields at school-age in children treated with vigabatrin in infancy. Epilepsia 2009, 50:206–216.CrossRefPubMedGoogle Scholar
  58. 58.
    Pearl P, Vezina LG, Saneto RP, et al.: Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia 2009, 50:184–194.CrossRefPubMedGoogle Scholar
  59. 59.
    Wheless JW, Carmant L, Bebin M, et al.: Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy. Epilepsia 2009, 50:195–205.CrossRefPubMedGoogle Scholar
  60. 60.
    Ben-Menachem E: Viagabatrin’s complicated journey—to be or not to be? Epilepsy Curr 2009, 9:130–132.CrossRefPubMedGoogle Scholar
  61. 61.
    Sabril [prescribing information]. Deerfield, IL: Lundbeck Inc.; 2010.Google Scholar
  62. 62.
    Brodie JD, Case BG, Figueroa E, et al.: Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees. Am J Psychiatry 2009, 166(11):1269–1277.CrossRefPubMedGoogle Scholar
  63. 63.
    Zwanzger P, Baghai T, Boerner RJ, et al.: Anxiolytic effects of vigabatrin in panic disorder. J Clin Psychopharmacol 2001, 21(5):539–540.CrossRefPubMedGoogle Scholar
  64. 64.
    Vermeij FH, van Doorn PA, Busch HF: Improvement of stiff-man syndrome with vigabatrin. Lancet 1996, 348:612.CrossRefPubMedGoogle Scholar
  65. 65.
    Prevett MC, Brown P, Duncan JS: Improvement of stiff-man syndrome with vigabatrin. Neurology 1997, 48:1133–1134.PubMedGoogle Scholar
  66. 66.
    Jaeken J, DeCock P, Casaer P: Vigabatrin as spasmolytic drug. Lancet 1991, 338:1603.CrossRefPubMedGoogle Scholar
  67. 67.
    Malmgren K, Hedström A, Granqvist R, et al.: Cost analysis of epilepsy surgery and of vigabatrin treatment in patients with refractory partial epilepsy. Epilepsy Res 1996, 25(3):199–207.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.The Children’s HospitalAuroraUSA

Personalised recommendations