Current Neurology and Neuroscience Reports

, Volume 10, Issue 4, pp 308–318 | Cite as

Update on Anticonvulsant Drugs

Article

Abstract

In 2009, the US Food and Drug Administration approved three medications for the treatment of epilepsy: rufinamide, lacosamide, and vigabatrin. In addition, extended-release formulations of lamotrigine and levetiracetam were approved recently. When added to the dozen medications for treating epilepsy, the choice is a luxury in terms of additional options, but also a challenge for practitioners to use them all with expertise. Recently, there has been much interest surrounding medications for epilepsy and their possible association with osteoporosis, safety during pregnancy, biological equivalence to generic versions, and possible association with higher rates of suicidality. This review discusses these issues and provides a current overview for the medical management of epilepsy.

Keywords

Epilepsy Treatment Medications Anticonvulsant Suicide Pregnancy Generics Hypersensitivity syndrome Therapeutic monitoring Bone health Lacosamide Rufinamide Vigabatrin 

References

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

  1. 1.
    LaRoche SM, Helmers SL: The new antiepileptic drugs: scientific review. JAMA 2004, 291:605–614.CrossRefPubMedGoogle Scholar
  2. 2.
    Marson AG, Al-Kharusi AM, Alwaidh M, et al.: The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet 2007, 369:1016–1026.CrossRefPubMedGoogle Scholar
  3. 3.
    Marson AG, Appleton R, Baker GA, et al.: A randomised controlled trial examining the longer-term outcomes of standard versus new antiepileptic drugs. The SANAD trial. Health Technol Assess 2007, 11:iii–iv, ix–x, 1–134.Google Scholar
  4. 4.
    Montouris G, Abou-Khalil B: The first line of therapy in a girl with juvenile myoclonic epilepsy: should it be valproate or a new agent? Epilepsia 2009, 50(Suppl 8):16–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Panayiotopoulos CP, Obeid T, Tahan AR: Juvenile myoclonic epilepsy: a 5-year prospective study. Epilepsia 1994, 35:285–296.CrossRefPubMedGoogle Scholar
  6. 6.
    Marson AG, Al-Kharusi AM, Alwaidh M, et al.: The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial. Lancet 2007, 369:1000–1015.CrossRefPubMedGoogle Scholar
  7. 7.
    Rowan AJ, Ramsay RE, Collins JF, et al.: New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology 2005, 64:1868–1873.CrossRefPubMedGoogle Scholar
  8. 8.
    • French JA, Kanner AM, Bautista J, et al.: Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004, 62:1261–1273. Along with Part I by the same authors [9•], this article reviews the evidence-based data for the use of AEDs in specific clinical situations. Although often there is a lack of high-quality published data to support the use of medications that have had good anecdotal results, this review lists and rates the evidence available for most of the modern AEDs.Google Scholar
  9. 9.
    • French JA, Kanner AM, Bautista J, et al.: Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004, 62:1252–1260. This is the first part of a two-part article by the same group.Google Scholar
  10. 10.
    Glauser T, Ben-Menachem E, Bourgeois B, et al.: ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006, 47:1094–1120.CrossRefPubMedGoogle Scholar
  11. 11.
    Kwan P, Brodie MJ: Effectiveness of first antiepileptic drug. Epilepsia 2001, 42:1255–1260.CrossRefPubMedGoogle Scholar
  12. 12.
    Kanner AM, Balabanov AJ: The use of monotherapy in patients with epilepsy: an appraisal of the new antiepileptic drugs. Curr Neurol Neurosci Rep 2005, 5:322–328.CrossRefPubMedGoogle Scholar
  13. 13.
    Kwan P, Brodie MJ: Epilepsy after the first drug fails: substitution or add-on? Seizure 2000, 9:464–468.CrossRefPubMedGoogle Scholar
  14. 14.
    • Liow K, Barkley GL, Pollard JR, et al.: Position statement on the coverage of anticonvulsant drugs for the treatment of epilepsy. Neurology 2007, 68:1249–1250. Neurologists should know about this statement by the American Academy of Neurology.Google Scholar
  15. 15.
    •• Gidal BE, Tomson T: Debate: substitution of generic drugs in epilepsy: is there cause for concern? Epilepsia 2008, 49(Suppl 9):56–62. This is an excellent review of both sides of the argument.Google Scholar
  16. 16.
    Patsalos PN, Berry DJ, Bourgeois BF, et al.: Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008, 49:1239–1276.CrossRefPubMedGoogle Scholar
  17. 17.
    Chiou CC, Yang LC, Hung SI, et al.: Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan. J Eur Acad Dermatol Venereol 2008, 22:1044–1049.CrossRefPubMedGoogle Scholar
  18. 18.
    Newell BD, Moinfar M, Mancini AJ, Nopper AJ: Retrospective analysis of 32 pediatric patients with anticonvulsant hypersensitivity syndrome (ACHSS). Pediatr Dermatol 2009, 26:536–546.CrossRefPubMedGoogle Scholar
  19. 19.
    Arif H, Buchsbaum R, Weintraub D, et al.: Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology 2007, 68:1701–1709.CrossRefPubMedGoogle Scholar
  20. 20.
    Hirsch LJ, Arif H, Nahm EA, et al.: Cross-sensitivity of skin rashes with antiepileptic drug use. Neurology 2008, 71:1527–1534.CrossRefPubMedGoogle Scholar
  21. 21.
    Franciotta D, Kwan P, Perucca E: Genetic basis for idiosyncratic reactions to antiepileptic drugs. Curr Opin Neurol 2009, 22:144–149.CrossRefPubMedGoogle Scholar
  22. 22.
    •• Hesdorffer DC, Kanner AM: The FDA alert on suicidality and antiepileptic drugs: fire or false alarm? Epilepsia 2009, 50:978–986. The authors discuss insights into the process by which the FDA alert came about, some criticisms of it, and, most importantly, constructive suggestions to integrate into clinical practice.Google Scholar
  23. 23.
    Shneker BF, Cios JS, Elliott JO: Suicidality, depression screening, and antiepileptic drugs: reaction to the FDA alert. Neurology 2009, 72:987–991.CrossRefPubMedGoogle Scholar
  24. 24.
    •• Verrotti A, Coppola G, Parisi P, et al.: Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosurg 2010, 112:1–10. This is a succinct review of bone metabolism and a summary of data for the effects of each AED on bone health.Google Scholar
  25. 25.
    Coppola G, Fortunato D, Auricchio G, et al.: Bone mineral density in children, adolescents, and young adults with epilepsy. Epilepsia 2009, 50:2140–2146.CrossRefPubMedGoogle Scholar
  26. 26.
    Meador K, Reynolds MW, Crean S, et al.: Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res 2008, 81:1–13.CrossRefPubMedGoogle Scholar
  27. 27.
    McVearry KM, Gaillard WD, VanMeter J, Meador KJ: A prospective study of cognitive fluency and originality in children exposed in utero to carbamazepine, lamotrigine, or valproate monotherapy. Epilepsy Behav 2009, 16:609–616.CrossRefPubMedGoogle Scholar
  28. 28.
    •• Harden CL, Hopp J, Ting TY, et al.: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): I. obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009, 50:1229–1236. This three-part series should be reviewed by all clinical neurologists because it represents the current standard of care for using AEDs before, during, and after pregnancy.Google Scholar
  29. 29.
    Harden CL, Meador KJ, Pennell PB, et al.: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): II. teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009, 50:1237–1246.CrossRefPubMedGoogle Scholar
  30. 30.
    Harden CL, Pennell PB, Koppel BS, et al.: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): III. vitamin K, folic acid, blood levels, and breast-feeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009, 50:1247–1255.CrossRefPubMedGoogle Scholar
  31. 31.
    Chen YH, Chiou HY, Lin HC, Lin HL: Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 2009, 66:979–984.CrossRefPubMedGoogle Scholar
  32. 32.
    Crawford P: Epilepsy and pregnancy. Seizure 2002, 11(Suppl A):212–219.Google Scholar
  33. 33.
    Tomson T, Palm R, Kallen K, et al.: Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia 2007, 48:1111–1116.CrossRefPubMedGoogle Scholar
  34. 34.
    Glauser T, Kluger G, Sachdeo R, et al.: Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008, 70:1950–1958.CrossRefPubMedGoogle Scholar
  35. 35.
    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 2009, 50:1899–1909.CrossRefPubMedGoogle Scholar
  36. 36.
    Kluger G, Kurlemann G, Haberlandt E, et al.: Effectiveness and tolerability of rufinamide in children and adults with refractory epilepsy: first European experience. Epilepsy Behav 2009, 14:491–495.CrossRefPubMedGoogle Scholar
  37. 37.
    Halasz P, Kalviainen R, Mazurkiewicz-Beldzinska M, et al.: Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia 2009, 50:443–453.CrossRefPubMedGoogle Scholar
  38. 38.
    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, 48:1308–1317.CrossRefPubMedGoogle Scholar
  39. 39.
    Doty P, Rudd GD, Stoehr T, Thomas D: Lacosamide. Neurotherapeutics 2007, 4:145–148.CrossRefPubMedGoogle Scholar
  40. 40.
    Tilz C, Resch R, Hofer T, Eggers C: Successful treatment for refractory convulsive status epilepticus by parenteral lacosamide. Epilepsia 2010, 51:316–317.CrossRefPubMedGoogle Scholar
  41. 41.
    Naritoku DK, Warnock CR, Messenheimer JA, et al.: Lamotrigine extended-release as adjunctive therapy for partial seizures. Neurology 2007, 69:1610–1618.CrossRefPubMedGoogle Scholar
  42. 42.
    Tompson DJ, Ali I, Oliver-Willwong R, et al.: Steady-state pharmacokinetics of lamotrigine when converting from a twice-daily immediate-release to a once-daily extended-release formulation in subjects with epilepsy (The COMPASS Study). Epilepsia 2008, 49:410–417.CrossRefPubMedGoogle Scholar
  43. 43.
    Christensen J, Petrenaite V, Atterman J, et al.: Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 2007, 48:484–489.CrossRefPubMedGoogle Scholar
  44. 44.
    Richy FF, Banerjee S, Brabant Y, Helmers S: Levetiracetam extended release and levetiracetam immediate release as adjunctive treatment for partial-onset seizures: an indirect comparison of treatment-emergent adverse events using meta-analytic techniques. Epilepsy Behav 2009, 16:240–245.CrossRefPubMedGoogle Scholar
  45. 45.
    Ulloa CM, Towfigh A, Safdieh J: Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures. Neuropsychiatr Dis Treat 2009, 5:467–476.PubMedGoogle Scholar
  46. 46.
    Peltola J, Coetzee C, Jimenez F, et al.: Once-daily extended-release levetiracetam as adjunctive treatment of partial-onset seizures in patients with epilepsy: a double-blind, randomized, placebo-controlled trial. Epilepsia 2009, 50:406–414.CrossRefPubMedGoogle Scholar
  47. 47.
    Helmstaedter C, Fritz NE, Kockelmann E, et al.: Positive and negative psychotropic effects of levetiracetam. Epilepsy Behav 2008, 13:535–541.CrossRefPubMedGoogle Scholar
  48. 48.
    Major P, Greenberg E, Khan A, Thiele EA: Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: preliminary results. Epilepsy Behav 2008, 13:557–559.CrossRefPubMedGoogle Scholar
  49. 49.
    Rossi S, Mataluni G, Codeca C, et al.: Effects of levetiracetam on chronic pain in multiple sclerosis: results of a pilot, randomized, placebo-controlled study. Eur J Neurol 2009, 16:360–366.CrossRefPubMedGoogle Scholar
  50. 50.
    Mintzer S, Skidmore CT, Abidin CJ, et al.: Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol 2009, 65:448–456.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Columbia Comprehensive Epilepsy Center, Department of NeurologyColumbia UniversityNew YorkUSA

Personalised recommendations