抗癫痫发作药物不良反应管理指南（2023）

doi:10.7499/j.issn.1008-8830.2306016

摘要
图/表
参考文献(79)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (724 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要癫痫是一种常见的神经系统疾病，病因复杂，发病机制尚未明确。为规范抗癫痫发作药物（anti-seizure medication, ASM）不良反应的管理，中国抗癫痫协会青年委员会联合中国抗癫痫协会精准医学与药物不良反应监测专业委员会组织制定了“抗癫痫发作药物不良反应管理指南（2023）”，对于ASM在神经精神系统、心血管系统及胎儿方面的不良反应管理，解答了13个临床问题，以期指导我国各医疗机构的癫痫专科、儿童神经科、神经内科、神经外科医务工作者的临床实践。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	中国抗癫痫协会青年委员会
	中国抗癫痫协会精准医学与药物不良反应监测专业委员会

关键词 ：抗癫痫发作药物, 癫痫, 不良反应, 管理指南

Abstract：Epilepsy is a prevalent neurological disorder with a complex etiology and an unclear pathogenesis. In order to standardize the management of adverse effects caused by anti-seizure medications (ASMs), the Youth Committee of the Chinese Association Against Epilepsy (CAAE), in collaboration with the CAAE Precision Medicines and Adverse Effect Monitoring Committee, has developed a guideline: guidelines for the management of adverse effects of anti-seizure medications (2023). This guideline addresses 13 clinical questions related to the management of adverse effects of ASMs in the nervous system, cardiovascular system, and fetus. Its primary objective is to provide guidance to medical professionals specializing in pediatric neurology, neurology, and neurosurgery in China, and to facilitate their clinical practice.

Key words： Anti-seizure medication Epilepsy Adverse effect Management guideline

收稿日期: 2023-06-05

通讯作者: 彭镜，女，主任医师，教授，中南大学湘雅医院儿科，Email：pengjing4346@163.com E-mail: pengjing4346@163.com

引用本文:

中国抗癫痫协会青年委员会,中国抗癫痫协会精准医学与药物不良反应监测专业委员会. 抗癫痫发作药物不良反应管理指南（2023）[J]. 中国当代儿科杂志, 2023, 25(9): 889-900.

Youth Committee of the Chinese Association Against Epilepsy (CAAE),CAAE Precision Medicines and Adverse Effect Monitoring Committee. Guidelines for the management of adverse effects of anti-seizure medications (2023)[J]. CJCP, 2023, 25(9): 889-900.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2306016 或 http://www.zgddek.com/CN/Y2023/V25/I9/889

	Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults[J]. Lancet, 2019, 393(10172): 689-701. PMID: 30686584. DOI: 10.1016/S0140-6736(18)32596-0.
	ukawski K, Czuczwar SJ. Understanding mechanisms of drug resistance in epilepsy and strategies for overcoming it[J]. Expert Opin Drug Metab Toxicol, 2021, 17(9): 1075-1090. PMID: 34310255. DOI: 10.1080/17425255.2021.1959912.
	Chen Y, Yang K, Maru?ic A, et al. A reporting tool for practice guidelines in health care: the RIGHT statement[J]. Ann Intern Med, 2017, 166(2): 128-132. PMID: 27893062. DOI: 10.7326/M16-1565.
	4 EEBM. OCEBM levels of evidence[EB/OL]. [2023-07-25]. https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence.
	Brouwers MC, Kho ME, Browman GP, et al. AGREE II: advancing guideline development, reporting and evaluation in health care[J]. CMAJ, 2010, 182(18): E839-E842. PMID: 20603348. PMCID: PMC3001530. DOI: 10.1503/cmaj.090449.
	6 WHO. WHO handbook for guideline development, 2nd Edition[EB/OL]. (2014-12-18)[2022-03-22]. https://www.who.int/publications-detail-redirect/9789241548960.
	Haut SR, Katz M, Masur J, et al. Seizures in the elderly: impact on mental status, mood, and sleep[J]. Epilepsy Behav, 2009, 14(3): 540-544. PMID: 19189862. PMCID: PMC2695969. DOI: 10.1016/j.yebeh.2009.01.005.
	Ho PH, Leung WCY, Leung IYH, et al. Factors associated with depression in people with epilepsy: a retrospective case-control analysis[J]. Hong Kong Med J, 2020, 26(4): 311-317. PMID: 32611830. DOI: 10.12809/hkmj198310.
	Tegegne MT, Mossie TB, Awoke AA, et al. Depression and anxiety disorder among epileptic people at Amanuel Specialized Mental Hospital, Addis Ababa, Ethiopia[J]. BMC Psychiatry, 2015, 15: 210. PMID: 26328614. PMCID: PMC4556015. DOI: 10.1186/s12888-015-0589-4.
	Hendriks MP, Aldenkamp AP, Alpherts WC, et al. Relationships between epilepsy-related factors and memory impairment[J]. Acta Neurol Scand, 2004, 110(5): 291-300. PMID: 15476457. DOI: 10.1111/j.1600-0404.2004.00319.x.
	Majkowski J, Neto W, Wapenaar R, et al. Time course of adverse events in patients with localization-related epilepsy receiving topiramate added to carbamazepine[J]. Epilepsia, 2005, 46(5): 648-653. PMID: 15857429. DOI: 10.1111/j.1528-1167.2005.35904.x.
	Bresnahan R, Hounsome J, Jette N, et al. Topiramate add-on therapy for drug-resistant focal epilepsy[J]. Cochrane Database Syst Rev, 2019, 10(10): CD001417. PMID: 31642054. PMCID: PMC6806021. DOI: 10.1002/14651858.CD001417.pub4.
	13 O'Connor J, Levy P, Wilson SS. Levetiracetam is as effective as phenytoin for status epilepticus with less adverse events in the ED[J]. Crit Care Med, 2015, 43(12): 6. DOI: 10.1097/01.ccm.0000473848.40708.ea.
	Delanty N, Jones J, Tonner F. Adjunctive levetiracetam in children, adolescents, and adults with primary generalized seizures: open-label, noncomparative, multicenter, long-term follow-up study[J]. Epilepsia, 2012, 53(1): 111-119. PMID: 22050371. DOI: 10.1111/j.1528-1167.2011.03300.x.
	Sankar R, Ramsay E, McKay A, et al. A multicenter, outpatient, open-label study to evaluate the dosing, effectiveness, and safety of topiramate as monotherapy in the treatment of epilepsy in clinical practice[J]. Epilepsy Behav, 2009, 15(4): 506-512. PMID: 19643672. DOI: 10.1016/j.yebeh.2009.06.021.
	16 Mohan P, Gupta P, Tripathi M, et al. Adverse effect profile of anti epileptic drugs in persons with epilepsy in India: a cross sectional study[J]. Clin Ther, 2015, 37(8): e135-e136. DOI: 10.1016/j.clinthera.2015.05.387.
	Steinhoff BJ, Klein P, Klitgaard H, et al. Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: a systematic review[J]. Epilepsy Behav, 2021, 118: 107939. PMID: 33839453. DOI: 10.1016/j.yebeh.2021.107939.
	Harbord MG. Significant anticonvulsant side-effects in children and adolescents[J]. J Clin Neurosci, 2000, 7(3): 213-216. PMID: 10833618. DOI: 10.1054/jocn.1999.0190.
	19 Bj?rk MH, Veiby G, Reiter S, et al. Pregnant women with epilepsy: is the risk of peripartum psychiatric symptoms increased?—a prospective, population based cohort study[J]. J Neurol Sci, 2013, 333(S1): E46. DOI: 10.1016/j.jns.2013.07.165.
	Guilfoyle SM, Wagner JL, Smith G, et al. Early screening and identification of psychological comorbidities in pediatric epilepsy is necessary[J]. Epilepsy Behav, 2012, 25(4): 495-500. PMID: 23153713. DOI: 10.1016/j.yebeh.2012.09.041.
	21 Jovic N, Belacevic M. Levetiracetam-induced psychiatric adverse events in children with epilepsy[J]. Eur Neuropsychopharmacol, 2013, 23(Suppl 2): S601. DOI: 10.1016/S0924-977X(13)70956-8.
	Mula M, Trimble MR, Lhatoo SD, et al. Topiramate and psychiatric adverse events in patients with epilepsy[J]. Epilepsia, 2003, 44(5): 659-663. PMID: 12752464. DOI: 10.1046/j.1528-1157.2003.05402.x.
	Lattanzi S, Cagnetti C, Foschi N, et al. Adjunctive perampanel in older patients with epilepsy: a multicenter study of clinical practice[J]. Drugs Aging, 2021, 38(7): 603-610. PMID: 34075567. PMCID: PMC8266697. DOI: 10.1007/s40266-021-00865-3.
	Kanner AM, Wuu J, Faught E, et al. A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events[J]. Epilepsy Behav, 2003, 4(5): 548-552. PMID: 14527497. DOI: 10.1016/j.yebeh.2003.07.007.
	Juhl S, Rubboli G. Add-on perampanel and aggressive behaviour in severe drug-resistant focal epilepsies[J]. Funct Neurol, 2017, 32(4): 215-220. PMID: 29336297. PMCID: PMC5762107.
	26 Fain R, Chung S, Yang H, et al. Aggression adverse events with concomitant levetiracetam use in perampanel phase III partial-onset seizure clinical studies[J]. Epilepsy Curr, 2015, 15: 321-322. DOI: 10.1002/central/CN-01081287.
	Cardenas JF, Rho JM, Ng YT. Reversible lamotrigine-induced neurobehavioral disturbances in children with epilepsy[J]. J Child Neurol, 2010, 25(2): 182-187. PMID: 19494356. DOI: 10.1177/0883073809336874.
	Zaccara G, Giovannelli F, Maratea D, et al. Neurological adverse events of new generation sodium blocker antiepileptic drugs. Meta-analysis of randomized, double-blinded studies with eslicarbazepine acetate, lacosamide and oxcarbazepine[J]. Seizure, 2013, 22(7): 528-536. PMID: 23623245. DOI: 10.1016/j.seizure.2013.03.016.
	Wen X, Meador KJ, Loring DW, et al. Is antiepileptic drug use related to depression and suicidal ideation among patients with epilepsy?[J]. Epilepsy Behav, 2010, 19(3): 494-500. PMID: 20880757. DOI: 10.1016/j.yebeh.2010.08.030.
	Betts T, Goodwin G, Withers RM, et al. Human safety of lamotrigine[J]. Epilepsia, 1991, 32 (Suppl 2): S17-S21. PMID: 1837776. DOI: 10.1111/j.1528-1157.1991.tb05881.x.
	Namazi S, Borhani-Haghighi A, Karimzadeh I. Adverse reactions to antiepileptic drugs in epileptic outpatients: a cross-sectional study in Iran[J]. Clin Neuropharmacol, 2011, 34(2): 79-83. PMID: 21412202. DOI: 10.1097/WNF.0b013e318210ece0.
	R?sche J, Kundt G, Weber R, et al. The impact of antiepileptic polytherapy on mood and cognitive function[J]. Acta Neurol Belg, 2011, 111(1): 29-32. PMID: 21510230.
	Lee JJ, Song HS, Hwang YH, et al. Psychiatric symptoms and quality of life in patients with drug-refractory epilepsy receiving adjunctive levetiracetam therapy[J]. J Clin Neurol, 2011, 7(3): 128-136. PMID: 22087206. PMCID: PMC3212598. DOI: 10.3988/jcn.2011.7.3.128.
	34 Rathore JS, Tesar GE, Obuchowski N, et al. Correlations of PHQ-9 with NDDI-E in epilepsy patients: a pilot study[J]. Epilepsy Curr, 2013, 13: 258. DOI: 10.5698/1535-7511-13.s1.
	Joshi R, Tripathi M, Gupta P, et al. Depression in patients receiving pharmacotherapy for epilepsy: an audit in a tertiary care centre[J]. Pharmacol Rep, 2019, 71(5): 848-854. PMID: 31398575. DOI: 10.1016/j.pharep.2019.04.021.
	36 张静, 魏红艳, 左艳芳, 等. 抗癫痫药和脑电图放电指数对癫痫患儿认知功能的影响[J]. 临床和实验医学杂志, 2019, 18(15): 1625-1628. DOI: 10.3969/j.issn.1671-4695.2019.15.017.
	Yang L, Dong XZ, Cui XH, et al. Comparison of the efficacy and safety of levetiracetam and phenytoin in the treatment of established status epilepticus: a systematic review and meta-analysis[J]. J Clin Neurosci, 2021, 89: 422-429. PMID: 34053822. DOI: 10.1016/j.jocn.2021.05.004.
	Yang C, Peng Y, Zhang L, et al. Safety and tolerability of lacosamide in patients with epilepsy: a systematic review and meta-analysis[J]. Front Pharmacol, 2021, 12: 694381. PMID: 34616294. PMCID: PMC8488108. DOI: 10.3389/fphar.2021.694381.
	Steinhoff BJ, Eckhardt K, Doty P, et al. A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures[J]. Epilepsy Behav, 2016, 58: 35-43. PMID: 27054272. DOI: 10.1016/j.yebeh.2016.02.041.
	Davidson KE, Newell J, Alsherbini K, et al. Safety and efficiency of intravenous push lacosamide administration[J]. Neurocrit Care, 2018, 29(3): 491-495. PMID: 29949010. DOI: 10.1007/s12028-018-0560-6.
	41 Cook R, Whiteside C, Alsherbini K, et al. Adverse events relating to the use of midazolam infusions for refractory status epilepticus[J]. Crit Care Med, 2019, 47(1): 344. DOI: 10.1097/01.ccm.0000551479.49808.1a.
	Brandt C, Klein P, Badalamenti V, et al. Safety and tolerability of adjunctive brivaracetam in epilepsy: in-depth pooled analysis[J]. Epilepsy Behav, 2020, 103(Pt A): 106864. PMID: 31937513. DOI: 10.1016/j.yebeh.2019.106864.
	Kim HK, Hwang IG, Koh IS, et al. Incidence and risk factors of hypotension after intravenous fosphenytoin administration[J]. J Clin Pharm Ther, 2017, 42(5): 561-566. PMID: 28439951. DOI: 10.1111/jcpt.12537.
	44 Torian S, Jones GM. 910: high-dose intravenous push lacosamide: safety and efficiency in administration[J]. Crit Care Med, 2022, 50(1): 452. DOI: 10.1097/01.ccm.0000809964.67465.f7.
	Arnold S, Laloyaux C, Schulz AL, et al. Long-term safety and efficacy of brivaracetam in adults with focal seizures: results from an open-label, multinational, follow-up trial[J]. Epilepsy Res, 2020, 166: 106404. PMID: 32731118. DOI: 10.1016/j.eplepsyres.2020.106404.
	Guldiken B, Rémi J, Noachtar S. Cardiovascular adverse effects of phenytoin[J]. J Neurol, 2016, 263(5): 861-870. PMID: 26645393. DOI: 10.1007/s00415-015-7967-1.
	47 O'Brien J, Klaus S, Jain D, et al. Telemetry monitoring in an epilepsy monitoring unit reveals new arrhythmias in patients on antiepileptic drugs with confirmed arrhythmic side effects[J]. Europace, 2018, 20: i17. DOI: 10.1093/europace/euy015.040.
	Lee-Lane E, Torabi F, Lacey A, et al. Epilepsy, antiepileptic drugs, and the risk of major cardiovascular events[J]. Epilepsia, 2021, 62(7): 1604-1616. PMID: 34046890. DOI: 10.1111/epi.16930.
	Weeke LC, Schalkwijk S, Toet MC, et al. Lidocaine-associated cardiac events in newborns with seizures: incidence, symptoms and contributing factors[J]. Neonatology, 2015, 108(2): 130-136. PMID: 26111505. DOI: 10.1159/000430767.
	50 Yi?in AK, Alay MT, Seven M. Fetal outcomes of anti-epileptic drug use in pregnancy: teratologic approach[J]. Turk J Neurol, 2021, 27: 27-33. DOI: 10.4274/tnd.2020.42402.
	Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child[J]. Cochrane Database Syst Rev, 2016, 11(11): CD010224. PMID: 27819746. PMCID: PMC6465055. DOI: 10.1002/14651858.CD010224.pub2.
	Veroniki AA, Cogo E, Rios P, et al. Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes[J]. BMC Med, 2017, 15(1): 95. PMID: 28472982. PMCID: PMC5418725. DOI: 10.1186/s12916-017-0845-1.
	Wide K, Winbladh B, Tomson T, et al. Psychomotor development and minor anomalies in children exposed to antiepileptic drugs in utero: a prospective population-based study[J]. Dev Med Child Neurol, 2000, 42(2): 87-92. PMID: 10698324. DOI: 10.1017/s0012162200000177.
	Margulis AV, Mitchell AA, Gilboa SM, et al. Use of topiramate in pregnancy and risk of oral clefts[J]. Am J Obstet Gynecol, 2012, 207(5): 405.e1-405.e7. PMID: 22917484. PMCID: PMC3484193. DOI: 10.1016/j.ajog.2012.07.008.
	Almgren M, K?llén B, Lavebratt C. Population-based study of antiepileptic drug exposure in utero: influence on head circumference in newborns[J]. Seizure, 2009, 18(10): 672-675. PMID: 19828334. DOI: 10.1016/j.seizure.2009.09.002.
	Jentink J, Dolk H, Loane MA, et al. Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study[J]. BMJ, 2010, 341: c6581. PMID: 21127116. PMCID: PMC2996546. DOI: 10.1136/bmj.c6581.
	Farmen AH, Grundt J, Tomson T, et al. Intrauterine growth retardation in foetuses of women with epilepsy[J]. Seizure, 2015, 28: 76-80. PMID: 25797889. DOI: 10.1016/j.seizure.2015.02.026.
	Veiby G, Daltveit AK, Engelsen BA, et al. Fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy[J]. J Neurol, 2014, 261(3): 579-588. PMID: 24449062. DOI: 10.1007/s00415-013-7239-x.
	Vajda FJ, O'Brien TJ, Hitchcock A, et al. The Australian registry of anti-epileptic drugs in pregnancy: experience after 30 months[J]. J Clin Neurosci, 2003, 10(5): 543-549. PMID: 12948456. DOI: 10.1016/s0967-5868(03)00158-9.
	Wen X, Hartzema A, Delaney JA, et al. Combining adverse pregnancy and perinatal outcomes for women exposed to antiepileptic drugs during pregnancy, using a latent trait model[J]. BMC Pregnancy Childbirth, 2017, 17(1): 10. PMID: 28061833. PMCID: PMC5219655. DOI: 10.1186/s12884-016-1190-7.
	Artama M, Gissler M, Malm H, et al. Effects of maternal epilepsy and antiepileptic drug use during pregnancy on perinatal health in offspring: nationwide, retrospective cohort study in Finland[J]. Drug Saf, 2013, 36(5): 359-369. PMID: 23615755. DOI: 10.1007/s40264-013-0052-8.
	Titze K, Koch S, Helge H, et al. Prenatal and family risks of children born to mothers with epilepsy: effects on cognitive development[J]. Dev Med Child Neurol, 2008, 50(2): 117-122. PMID: 18177411. DOI: 10.1111/j.1469-8749.2007.02020.x.
	Tomson T, Battino D, Bonizzoni E, et al. Declining malformation rates with changed antiepileptic drug prescribing: an observational study[J]. Neurology, 2019, 93(9): e831-e840. PMID: 31391249. DOI: 10.1212/WNL.0000000000008001.
	Vajda FJ, O'Brien TJ, Lander CM, et al. Teratogenesis in repeated pregnancies in antiepileptic drug-treated women[J]. Epilepsia, 2013, 54(1): 181-186. PMID: 22882134. DOI: 10.1111/j.1528-1167.2012.03625.x.
	Viinikainen K, Heinonen S, Eriksson K, et al. Community-based, prospective, controlled study of obstetric and neonatal outcome of 179 pregnancies in women with epilepsy[J]. Epilepsia, 2006, 47(1): 186-192. PMID: 16417548. DOI: 10.1111/j.1528-1167.2006.00386.x.
	Hernández-Díaz S, Werler MM, Walker AM, et al. Folic acid antagonists during pregnancy and the risk of birth defects[J]. N Engl J Med, 2000, 343(22): 1608-1614. PMID: 11096168. DOI: 10.1056/NEJM200011303432204.
	Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry[J]. Lancet Neurol, 2011, 10(7): 609-617. PMID: 21652013. DOI: 10.1016/S1474-4422(11)70107-7.
	Mawer G, Clayton-Smith J, Coyle H, et al. Outcome of pregnancy in women attending an outpatient epilepsy clinic: adverse features associated with higher doses of sodium valproate[J]. Seizure, 2002, 11(8): 512-518. PMID: 12464511. DOI: 10.1016/s1059-1311(02)00135-8.
	Vajda FJ, Lander CM, Hitchcock A, et al. Changing Australian prescribing patterns for antiepileptic drugs in pregnancy and their possible consequences[J]. J Clin Neurosci, 2007, 14(7): 611-617. PMID: 17400456. DOI: 10.1016/j.jocn.2006.04.025.
	Harden C, Lu C. Epilepsy in pregnancy[J]. Neurol Clin, 2019, 37(1): 53-62. PMID: 30470275. DOI: 10.1016/j.ncl.2018.09.008.
	Battino D, Binelli S, Caccamo ML, et al. Malformations in offspring of 305 epileptic women: a prospective study[J]. Acta Neurol Scand, 1992, 85(3): 204-207. PMID: 1575005. DOI: 10.1111/j.1600-0404.1992.tb04029.x.
	Mawer G, Briggs M, Baker GA, et al. Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study[J]. Seizure, 2010, 19(2): 112-119. PMID: 20036166. PMCID: PMC2823982. DOI: 10.1016/j.seizure.2009.11.008.
	Campbell E, Devenney E, Morrow J, et al. Recurrence risk of congenital malformations in infants exposed to antiepileptic drugs in utero[J]. Epilepsia, 2013, 54(1): 165-171. PMID: 23167802. DOI: 10.1111/epi.12001.
	Cunnington MC. The international lamotrigine pregnancy registry update for the epilepsy foundation[J]. Epilepsia, 2004, 45(11): 1468. PMID: 15509254. DOI: 10.1111/j.0013-9580.2004.451105.x.
	Mawhinney E, Craig J, Morrow J, et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers[J]. Neurology, 2013, 80(4): 400-405. PMID: 23303847. DOI: 10.1212/WNL.0b013e31827f0874.
	Rauchenzauner M, Ehrensberger M, Prieschl M, et al. Generalized tonic-clonic seizures and antiepileptic drugs during pregnancy: a matter of importance for the baby?[J]. J Neurol, 2013, 260(2): 484-488. PMID: 22955634. DOI: 10.1007/s00415-012-6662-8.
	Thomas SV, Jeemon P, Pillai R, et al. Malformation risk of new anti-epileptic drugs in women with epilepsy; observational data from the Kerala registry of epilepsy and pregnancy (KREP)[J]. Seizure, 2021, 93: 127-132. PMID: 34740142. DOI: 10.1016/j.seizure.2021.10.015.
	Scheuerle AE, Holmes LB, Albano JD, et al. Levetiracetam pregnancy registry: final results and a review of the impact of registry methodology and definitions on the prevalence of major congenital malformations[J]. Birth Defects Res, 2019, 111(13): 872-887. PMID: 31124321. DOI: 10.1002/bdr2.1526.
	Sabers A, Dam M, A-Rogvi-Hansen B, et al. Epilepsy and pregnancy: lamotrigine as main drug used[J]. Acta Neurol Scand, 2004, 109(1): 9-13. PMID: 14653845. DOI: 10.1034/j.1600-0404.2003.00200.x.