Clinical features of the use of lamotrigine in pregnant women with epilepsy | Український Медичний Часопис

In order to study the existing world experience in the clinical use of lamotrigine as one of the most commonly prescribed antiepileptic drugs for women with epilepsy, including during pregnancy, as well as to provide practically significant recommendations on the peculiarities of its use to practicing neurologists, we carried out an information search articles and abstracts in the MEDLINE, The Cochrane Library, Google Scholar databases as of December 31, 2019 using keywords «safety», «antiepileptic drugs», «epilepsy», «pregnancy», «lamotrigine», «seizures», «congenital abnormalities». It was found that lamotrigine is one of the safest drugs for the treatment of epilepsy in women. The features of its use were studied and five of the most important, from our point of view, clinical recommendations to optimize the therapy are presented: a gradual transition to monotherapy with lamotrigine at the stage of pregnancy planning, taking high doses (5 mg) of folic acid from 3 months before conception to the end of the I trimester of pregnancy, regular clinical examination and monitoring of the drug in plasma, dose adjustment of lamotrigine in every trimester of pregnancy and a reduction in dosage after childbirth, avoiding breastfeeding of the newborn with a careful assesment of potential benefits and the possible risk of side effects.

References:

Adab N., Chadwick D.W. (2006) Management of women with epilepsy during pregnancy. Obstet. Gynaecol., 8: 20–25.
Angelis-Stoforidis P., Morgan D.J., O’Brien T.J. et al. (1999) Determination of lamotrigine in human plasma by high-performance liquid chromatography. J. Chromatogr. B. Biomed. Sci., 727: 113–118.
Ban L., Fleming K.M., Doyle P. et al. (2015) Congenital аnomalies in сhildren of mothers taking antiepileptic drugs with and without periconceptional high dose folic acid use: a population-based cohort study. PLoS ONE, 10(7): e0131130. https://doi.org/10.1371/journal.pone.0131130.
Banerjee P.N. (2009) The descriptive epidemiology of epilepsy. In: P.N. Banerjee, D. Filippi, W. Clen Hauser (Eds.). Epilepsy Res., 85: 31–45.
Bendtsen L., Zakrzewska J.M., Abbott J. et al. (2019) European Academy of Neurology guideline on trigeminal neuralgia. Eur. J. Neurol., 26(6): 831–849.
Benzeer A., Nagavamsidhar M., Qadrie Z.L. (2018) Epilepsy affecting women whole life — a review. IJPPR Human, 11(4): 268–281.
Betchel N.T., Saadabadi A. (2019) Lamotrigine (https://www.ncbi.nlm.nih.gov/books/NBK470442/).
Boggs J.G., Benbadis S.R. (2014) Women’s health and epilepsy (http://emedicine.medscape.com/article/1186482-overview#a3).
Brigo F., Igwe S.C., Lattanzi S. (2019) Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst. Rev., 2: CD003032.
Bromley R., Weston J., Adab N. et al. (2014) Treatment for epilepsy in pregnancy: neurodevelopmental outcomes in the child. Cochrane Database Syst. Rev., 10: CD010236. DOI: 10.1002/14651858.CD010236.pub2.
Burch J., Ciapponi A. (2019) How does lamotrigine compare with other antiepileptic drugs in terms of congenital malformations in children? (https://www.cochranelibrary.com/cca/doi/10.1002/cca.2537/full).
Christensen J., Grønborg T.K., Sørensen M.J. et al. (2013) Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA, 309(16): 1696–703. DOI: 10.1001/jama.2013.2270.
Dalili H., Nayeri F., Shariat M., Asgarzadeh L. (2015) Lamotrigine Effects on Breastfed Infants. Acta Med. Iran, 53(7): 393–394.
Drislane F., Coleman A., Schomer D. et al. (1994) Altered pulsatile secretion of luteinizing hormone in women with epilepsy. Neurology, 44: 306–310.
Drislane F.W., Coleman A.E., Schomer D.L. et al. (2002) Folic acid and epilepsy. Epilepsy Curr., 2(2): 31–34.
Dupont S. (2018) Specific aspects of the management of women with epilepsy. Presse Med., 47(3): 251–260. DOI: 10.1016/j. lpm.2018.01.020.
Edey S., Moran N., Nashef L. (2014) SUDEP and epilepsy-related mortality in pregnancy. Epilepsia, 55: e72–e74.
Harden C. (2008) Sexual dysfunction in women with epilepsy. Seizure: the journal of the British Epilepsy Association, 17: 131–135. 10.1016/j.seizure.2007.11.010.
Harden C.L., Leppik I. (2006) Optimizing therapy of seizures in women who use oral contraceptives. Neurology, 67(12 Suppl. 4): S56–S58.
Harden C.L., Meador K.J., Pennell P.B. et al. (2009a) Management issues for women with epilepsy — focus on pregnancy (an evi-dence-based review). II: Teratogenesis and perinatal outcomes. Epilepsia, 50(5): 1237–1246.
Harden C.L., Meador K.J., Pennell P.B. et al. (2009b) Practice parameter update: management issues for women with epilepsy — focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology, 73(2): 133–141.
Harden C.L., Pennell P.B., Koppel B.S. et al. (2009с) Management issues for women with epilepsy — focus on pregnancy (an evi-dence-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 Socie-ty. Epilepsia, 50(5): 1247–1255.
Hauser W.A., Annegers J.F., Kurland L.T. (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935–1984. Epilepsia, 34: 453–458 (https://doi.org/10.1111/j.1528-1157.1993.tb02586.x).
Herzog A.G. (2006) Menstrual disorders in women with epilepsy. Neurology, 66(Suppl. 3): S23–S28.
Hjorth S., Bromley R., Ystrom E. et al. (2019) Use and validity of child neurodevelopment outcome measures in studies on prenatal exposure to psychotropic and analgesic medications — a systematic review. PLoS One, 14(7): e0219778. doi: 10.1371/journal.pone.0219778.
Jansen A.C., Andermann E. (2007) Progressive myoclonus tpilepsy, Lafora type. In: M.P. Adam, H.H. Ardinger, R.A. Pagon et al. (Eds.). GeneReviews®. University of Washington, Seattle, Seattle (WA).
Johannessen Landmark C., Patsalos P.N. (2010) Drug interactions involving the new second- and third-generation antiepileptic drugs. Expert. Rev. Neurother., 10(1): 119–140.
Kacirova I., Grundmann M., Brozmanova H. (2019) A short communication: lamotrigine levels in milk, mothers and breast-fed infants during the 1st postnatal month. Ther. Drug Monit., 41: 401–404.
Kjaer D., Horvath-Puhó E., Christensen J. et al. (2008) Antiepileptic drug use, folic acid supplementation, and congenital abnormalities: a population-based case — control study. BJOG, 115(1): 98–103.
Kotsopoulos I.A.W., Van Merode T., Kessels F.G.H. et al. (2002) Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia, 43: 1402–1409. https://doi.org/10.1046/ j.1528-1157.2002.t01-1-26901.x.
Lander C.M. (2008) Antiepileptic drugs in pregnancy and lactation. Aust. Prescriber., 31(3): 70–72.
Meador K.J., Baker G.A., Browning N. et al.; NEAD Study Group (2013) Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol., 12: 244–252.
Morrow J., Russell A., Guthrie E. et al. (2006) Systematic review and meta-analysis that provides a comprehensive summary of the effects of AED monotherapy and polytherapy on pregnancy outcomes. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J. Neurol. Neurosurg. Psychiatr., 77(2): 193–198.
Morrow J.I., Hunt S.J., Russell A.J. et al. (2009) Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register. J. Neurol. Neurosurg. Psychiatr., 80(5): 506–511.
Pariente G., Leibson T., Shulman T. et al. (2017) Pregnancy outcomes following in utero exposure to lamotrigine: a systematic review and meta-analysis. CNS Drugs 31, 439–450 (https://doi.org/10.1007/s40263-017-0433-0).
Reddy D.S. (2004) Pharmacology of catamenial epilepsy. Method find Clin. Pharmacol., 26(7): 547–561.
Sabers A. (2011) Algorithm for lamotrigine dose adjustment before, during, and after pregnancy. Acta Neurol. Scand., 126: e1–e4. 10.1111/j.1600-0404.2011.01627.x.
Sabers A., Ohman I., Christensen J., Tomson T. (2003) Oral contraceptives reduce lamotrigine plasma levels. Neurology, 61(4): 570–571.
Tomson T., Gram L., Sillanpaa M., Johannessen S.I. (Eds.) (1997) Epilepsy and pregnancy. Wrightson biomedical publishing LTD: Peters field, UK and Bristol, PA, USA, 215 p.
UK Epilepsy and Pregnancy Register (2016) http://www.epilepsyandpregnancy.co.uk/.
Vajda F.J. (2007) Monitoring antiepileptic drug therapy with serum level measurements. Med. J. Aust., 187: 581.
Vajda F.J., Dodd S., Horgan D. (2013) Lamotrigine in epilepsy, pregnancy and psychiatry — a drug for all seasons? J. Clin. Neurosci., 20(1): 13—16.
Vajda F.J., O’Brien T.J., Hitchcock A. et al. (2003) The Australian registry ofanti-epileptic drugs in pregnancy: experience after 30 months. J. Clin. Neurosci., 10: 543–549.
Vajda F.J., O’Brien T.J., Hitchcock A. et al. (2004) Critical relationship between sodium valproate dose and human teratogenicity: results of the Australian register of anti-epileptic drugs in pregnancy. J. Clin. Neurosci., 11: 854–858.
Veroniki A.A., Rios P., Cogo E. et al. (2017) Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open., 7(7): e017248. doi:10.1136/bmjopen-2017-017248.
Verrotti A., Striano P., Iapadre G. et al. (2018) The pharmacological management of Lennox-Gastaut syndrome and critical literature review. Seizure, 63: 17–25.
Voitiuk A.A. (2019) Epilepsy: age and gender aspects. Arch. Neurol. Neurosci., 3(4): ANN.MS.ID.000570.
Waaler P.E., Blom B.H., Skeidsvoll H., Mykletun A. (2000) Prevalence, classification, and severity of epilep. Epilepsia, 41: 802–810.
Weston J., Bromley R., Jackson C.F. et al. (2016) Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database of Systematic Reviews, Issue 11: CD010224. DOI: 10.1002/14651858.CD010224.pub2.