Advertisement

Antiepileptic Drug Therapy: Management Issues and Pregnancy

  • MJ Eadie
  • FJE Vajda

Abstract

This chapter draws on material discussed in earlier chapters in an attempt to provide a scientifically based discussion of the management of antiepileptic drug therapy in women with epilepsy who are planning pregnancy, while pregnant and in the postpartum period. The aim of the management is to maintain optimal control of epileptic seizures at all times while also minimising the risks to the foetus from developing structural malformations while still in utero and from encountering neurodevelopmental problems during infancy and childhood. The information regarding the management of antiepileptic drug therapy in pregnant women with epilepsy should also, for the most part, be applicable to the use of these drugs in pregnant women for indications other than epilepsy.

Keywords

Status Epilepticus Antiepileptic Drug Seizure Control Plasma Drug Concentration Postpartum Depression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Artama M, Auvinen A, Raudaskoski T, Isojarvi I, Isojarvi J (2005) Antiepileptic drug use of women with epilepsy and congenital malformations in the offspring. Neurology 64:1874–1878CrossRefPubMedGoogle Scholar
  2. Battino D, Tomson T, Bonizzoni E et al (2013) Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 54:1621–1627CrossRefPubMedGoogle Scholar
  3. Bianchi DW, Platt LD, Goldberg JD et al (2012) Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 119:890–901CrossRefPubMedGoogle Scholar
  4. Boon P, Engelborghs S, Hauman H et al (2012) Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update. Acta Neurol Belg 112:119–131PubMedCentralCrossRefPubMedGoogle Scholar
  5. Bromley RL, Mawer G, Clayton-Smith J, Baker GA, Liverpool and Manchester Neurodevelopment Group (2008) Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 71:1923–1924CrossRefPubMedGoogle Scholar
  6. Choi H, Morrell MJ (2003) Review of lamotrigine and its clinical applications in epilepsy. Exp Opin Pharmacother 4:243–251CrossRefGoogle Scholar
  7. Christensen J, Grønborg TK, Sørensen MJ, Schendel D, Parner ET, Pedersen LH, Vestergaard M (2013) Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 309:1696–1703PubMedCentralCrossRefPubMedGoogle Scholar
  8. Cohen MJ, Meador KJ, Browning N et al (2013) Fetal antiepileptic drug exposure: adaptive and emotional/behavioral functioning at age 6 years. Epilepsy Behav 29:308–315PubMedCentralCrossRefPubMedGoogle Scholar
  9. Costa AL, Lopes-Cendes I, Guerreiro CA (2005) Seizure frequency during pregnancy and the puerperium. Int J Gynaecol Obstet 88:148–149CrossRefPubMedGoogle Scholar
  10. Cummings C, Stewart M, Stevenson M, Morrow J, Nelson J (2011) Neurodevelopment of children exposed to lamotrigine, sodium valproate and carbamazepine. Arch Dis Child 96:643–647CrossRefPubMedGoogle Scholar
  11. Garfield SS, Armstrong SO (2012) Clinical and cost consequences of incorporating a novel non-invasive prenatal test into the diagnostic pathway for fetal trisomies. J Manage Care Med 15:34–41Google Scholar
  12. Gjerde IO, Strandjord RE, Ulstein M (1988) The course of epilepsy during pregnancy: a study of 78 cases. Acta Neurol Scand 78:198–205CrossRefPubMedGoogle Scholar
  13. Glauser T, Ben-Menachem E, Bourgeois B et al (2013) Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 54:551–563CrossRefPubMedGoogle Scholar
  14. Harden C, Hopp J, Ting TY et al (2009) Management issues for women with epilepsy – focus on pregnancy (an evidence-based review): 1. Obstetrical complications and change in seizure frequency. Epilepsia 50:1229–1236CrossRefPubMedGoogle Scholar
  15. Holmes LB, Mittendorf R, Shen A, Smith CR, Hernandez-Diaz S (2011) Fetal effects of anticonvulsant polytherapies. Arch Neurol 68:1275–1281CrossRefPubMedGoogle Scholar
  16. Kaneko S, Utami K, Kondo T et al (1992) Malformations in infants of mothers with epilepsy receiving antiepileptic drugs. Neurology 42(Suppl 5):68–74PubMedGoogle Scholar
  17. Knight AH, Rhind EG (1975) Epilepsy and pregnancy: a study of 153 pregnancies in 59 patients. Epilepsia 16:99–110CrossRefPubMedGoogle Scholar
  18. Koren G, Kennedy D (1999) Safe use of valproic acid during pregnancy [Motherisk Update]. Can Fam Physician 45:1451–1453PubMedCentralPubMedGoogle Scholar
  19. Kwan P, Brodie MJ (2004) Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia 45:1141–1149CrossRefPubMedGoogle Scholar
  20. Lindhout D, Omtzigt JG (1992) Pregnancy and the risk of teratogenicity. Epilepsia 33(Suppl 4):S41–S48CrossRefPubMedGoogle Scholar
  21. Mawer G, Briggs M, Baker GA et al (2010) Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure 19:112–119PubMedCentralCrossRefPubMedGoogle Scholar
  22. McGrath A, Sharpe L, Lah S, Parratt K (2014) Pregnancy-related knowledge and information needs of women with epilepsy: a systematic review. Epilepsy Behav 31:246–266CrossRefPubMedGoogle Scholar
  23. Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C (2008) Pregnancy outcomes in women with epilepsy: a systematic review and analysis of published pregnancy registers and cohorts. Epilepsy Res 81:1–13PubMedCentralCrossRefPubMedGoogle Scholar
  24. Meador KJ, Baker GA, Browning N et al (2009) Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 360:1597–1605PubMedCentralCrossRefPubMedGoogle Scholar
  25. Meador KJ, Baker GA, Browning N et al (2010) Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology 75:1954–1960PubMedCentralCrossRefPubMedGoogle Scholar
  26. Meador KJ, Baker GA, Browning N et al (2012) Effects of fetal antiepileptic drug exposure: outcomes at age 4.5 years. Neurology 78:1207–1214PubMedCentralCrossRefPubMedGoogle Scholar
  27. Meador KJ, Baker GA, Browning N et al (2013) Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years study): a prospective observational study. Lancet Neurol 12:244–252PubMedCentralCrossRefPubMedGoogle Scholar
  28. Meador KJ, Baker GA, Browning N et al (2014) Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA Pediatr 168:729–736PubMedCentralCrossRefPubMedGoogle Scholar
  29. Morrow J, Russell A, Guthrie E et al (2006) Malformation risk of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry 77:193–198PubMedCentralCrossRefPubMedGoogle Scholar
  30. Mula M, Trimble MR, Yuen A et al (2003) Psychiatric adverse events during levetiracetam therapy. Neurology 61:704–706CrossRefPubMedGoogle Scholar
  31. Nakane Y, Okuma T, Takahashi R et al (1980) Multi-institutional study on the teratogenicity and fetal toxicity of antiepileptic drugs: a report of a collaborative study group in Japan. Epilepsia 21:663–680CrossRefPubMedGoogle Scholar
  32. Pack AM (2006) Therapy insight: clinical management of pregnant women with epilepsy. Nat Clin Pract Neurol 2:190–200CrossRefPubMedGoogle Scholar
  33. Palomaki GE, Knight GJ, Ashwood ER, Best RG, Haddow JE (2013) Screening for Down syndrome in the United States: results of surveys in 2011 and 2012. Arch Pathol Lab Med 137:921–926CrossRefPubMedGoogle Scholar
  34. Patsalos PN (2000) Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther 85:77–85CrossRefPubMedGoogle Scholar
  35. Patsalos PN, Berry DJ, Bourgeois BF et al (2008) Antiepileptic drugs - best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, I.L.A.E. Commission on Therapeutic Strategies. Epilepsia 49:1239–1276CrossRefPubMedGoogle Scholar
  36. Pennell PB (2005) Using current evidence in selecting antiepileptic drugs for use during pregnancy. Epilepsy Curr 5(2):45–51PubMedCentralCrossRefPubMedGoogle Scholar
  37. Pennell PB, Peng L, Newport DJ et al (2008) Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology 70:2130–2136PubMedCentralCrossRefPubMedGoogle Scholar
  38. Perucca E (2001) Clinical pharmacology and therapeutic use of the new antiepileptic drugs. Fundam Clin Pharmacol 15:405–417CrossRefPubMedGoogle Scholar
  39. Perucca E (2005) An introduction to antiepileptic drugs. Epilepsia 46(Suppl 4):31–37CrossRefPubMedGoogle Scholar
  40. Sabers A (2009) Influences on seizure activity in pregnant women with epilepsy. Epilepsy Behav 15:230CrossRefPubMedGoogle Scholar
  41. Sabers A, Petrenaite V (2009) Seizure frequency in pregnant women treated with lamotrigine monotherapy. Epilepsia 50:2163–2166CrossRefPubMedGoogle Scholar
  42. Sabers A, Dam M, a-Rogvi-Hansen B et al (2004) Epilepsy and pregnancy: lamotrigine as main drug used. Acta Neurol Scand 109:9–13CrossRefPubMedGoogle Scholar
  43. Samrén EB, van Duijn CM, Koch S et al (1997) Maternal use of antiepileptic drugs and the risk of major congenital malformations: a joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 38:981–990CrossRefPubMedGoogle Scholar
  44. Schaffler L (1990) Epilepsy and pregnancy. Schweiz Med Wochenschr 120:1508–1516PubMedGoogle Scholar
  45. Schmidt D (1982) The effect of pregnancy on the natural history of epilepsy: review of the literature. In: Janz D, Bossi L, Dam M, Helge H, Richens A, Schmidt D (eds) Epilepsy, pregnancy, and the child. Raven, New York, pp 3–14Google Scholar
  46. Shorvon S (2002) Commentary. Antiepileptic drug therapy during pregnancy: the neurologist’s perspective Antiepileptic medication in pregnancy. J Med Genet 39:248–250PubMedCentralCrossRefPubMedGoogle Scholar
  47. Thomas SV (2011) Managing epilepsy in pregnancy. Neurol India 59:59–65CrossRefPubMedGoogle Scholar
  48. Tomson T, Battino D, French J et al (2007a) Antiepileptic drug exposure and major congenital malformations: the role of the pregnancy registries. Epilepsy Behav 11:277–282CrossRefPubMedGoogle Scholar
  49. Tomson T, Palm R, Kallen K et al (2007b) Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Nat Clin Pract Neurol 310:538–539Google Scholar
  50. Vajda FJE, Angelis-Stoforidis P, Eadie MJ (1999) Utility of plasma lamotrigine concentration: Concept of the plasma therapeutic range for individual patients. J Neurol 246(Suppl 1):185Google Scholar
  51. Vajda FJE, Lander CM, O’Brien TJ et al (2006a) Foetal malformations and seizure control: 52 months data reported from the Australian Register of Pregnancies. Eur J Neurol 13:645–654CrossRefPubMedGoogle Scholar
  52. Vajda F, Solinas C, Graham J, Hitchcock A, Eadie M (2006b) The case for lamotrigine monitoring in pregnancy. J Clin Neurosci 13:103–104CrossRefPubMedGoogle Scholar
  53. Vajda FJE, Hitchcock A, Graham J, O’Brien T, Lander C, Eadie M (2008) Seizure control in antiepileptic drug-treated pregnancy. Epilepsia 49:172–175CrossRefPubMedGoogle Scholar
  54. Vajda FJE, Dodd S, Horgan D (2010a) Lamotrigine in epilepsy, pregnancy and psychiatry – a drug for all seasons? J Clin Neurosci 20:13–16CrossRefGoogle Scholar
  55. Vajda F, Hitchcock A, Graham J, O’Brien T, Lander C, Eadie M (2010b) The teratogenic risk of antiepileptic drug polytherapy. Epilepsia 51:805–810CrossRefPubMedGoogle Scholar
  56. Vajda FJE, O’Brien TJ, Graham J, Lander CM, Eadie MJ (2013) Dose-dependency of fetal malformations associated with valproate. Neurology 81:999–1003CrossRefPubMedGoogle Scholar
  57. Vajda FJE, O’Brien T, Lander C, Graham J, Eadie M (2014) The efficacy of the newer antiepileptic drugs in controlling seizures in pregnancy. Epilepsia 55:1229–1234CrossRefPubMedGoogle Scholar
  58. Vajda FJ, O’Brien TJ, Graham J, Lander CM, Eadie MJ (2015) The outcomes of pregnancy in women with untreated epilepsy. Seizure 24:77–81CrossRefPubMedGoogle Scholar
  59. Veiby G, Daltveit AK, Schjølberg S et al (2013a) Exposure to antiepileptic drugs in utero and child development: a prospective population-based study. Epilepsia 54:1462–1472PubMedCentralCrossRefPubMedGoogle Scholar
  60. Veiby G, Engelsen BA, Gilhus NE (2013b) Early child development and exposure to antiepileptic drugs prenatally and through breastfeeding: a prospective cohort study on children of women with epilepsy. JAMA Neurol 70:1367–1374CrossRefPubMedGoogle Scholar
  61. Vidović MI, Della Marina BM (1994) Trimestral changes of seizure frequency in pregnant epileptic women. Acta Med Croatica 48:85–87PubMedGoogle Scholar
  62. Weintraub D, Buchsbaum R, Resor SR Jr, Hirsch LJ (2007) Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy Behav 10:105–110CrossRefPubMedGoogle Scholar
  63. Yerby M (2003) Management issues for women with epilepsy: neural tube defects and folic acid supplementation. Neurology 61(Suppl 2):S23–S26CrossRefPubMedGoogle Scholar
  64. Yerby MS, Kaplan P, Tran T (2004) Risks and management of pregnancy in women with epilepsy. Cleve Clin J Med 71(S25):825–837Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • MJ Eadie
    • 1
  • FJE Vajda
    • 2
  1. 1.Clinical Neurology and NeuropharmacologyUniversity of Queensland, and Honorary Consultant Neurologist, Royal Brisbane and Women’s HospitalBrisbaneAustralia
  2. 2.Department of Medicine and Neurology Director of the Australian Epilepsy and Pregnancy RegisterUniversity of Melbourne and Royal Melbourne HospitalMelbourneAustralia

Personalised recommendations