275
Views
0
CrossRef citations to date
0
Altmetric
Review

Targeting adverse effects of antiseizure medication on offspring: current evidence and new strategies for safety

, , , , , , & show all
Pages 141-156 | Received 10 Oct 2022, Accepted 01 Feb 2023, Published online: 12 Feb 2023

References

  • Devinsky O, Vezzani A, O’Brien TJ, et al. Epilepsy. Nat Rev Dis Primers. 2018 May;3(4):18024.
  • Thijs RD, Surges R, O’Brien TJ, et al. Epilepsy in adults. Lancet. 2019 Feb 16;393(10172):689–701.
  • Chen TS, Lai MC, Huang HI, et al. Immunity, ion channels and epilepsy. Int J Mol Sci. 2022 Jun 9;23:12.
  • Librizzi L, Noè F, Vezzani A, et al. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood-brain barrier damage. Ann Neurol. 2012 Jul;72(1):82–90.
  • Godale CM, Danzer SC. Signaling pathways and cellular mechanisms regulating mossy fiber sprouting in the development of epilepsy. Front Neurol. 2018;9:298.
  • Devinsky O, Vezzani A, Najjar S, et al. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 2013 Mar;36(3):174–184.
  • Pitkänen A, Lukasiuk K, Dudek FE, et al. Epileptogenesis. In: Holmes GL, Noebels JL, editors. Cold spring harb perspect med. 2015 Sep 18; Vol. 5. p. 10. Cold Spring Harbor, NY.
  • Henshall DC, Hamer HM, Pasterkamp RJ, et al. MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol. 2016 Dec;15(13):1368–1376.
  • Dingledine R, Coulter DA, Fritsch B, et al. Transcriptional profile of hippocampal dentate granule cells in four rat epilepsy models. Sci Data. 2017 May;9(4):170061.
  • Manford M. Recent advances in epilepsy. J Neurol. 2017 Aug;264(8):1811–1824.
  • Sauro KM, Wiebe S, Dunkley C, et al. The current state of epilepsy guidelines: a systematic review. Epilepsia. 2016 Jan;57(1):13–23.
  • Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004 Jul;5(7):553–564.
  • Sills GJ, Rogawski MA. Mechanisms of action of currently used antiseizure drugs. Neuropharmacology. 2020 May;15(168):107966.
  • Chen Z, Brodie MJ, Liew D, et al. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018 Mar 1;75(3):279–286.
  • Löscher W, The Pharmacology KP. Clinical efficacy of antiseizure medications: from bromide salts to cenobamate and beyond. CNS Drugs. 2021 Sep;35(9):935–963.
  • Global, regional, and national incidence, prevalence, and years lived with disability for. 310 diseases and injuries, 1990-2015: a systematic analysis for the global burden of disease study 2015. Lancet. 2016 Oct 8;388(10053):1545–1602.
  • Ngugi AK, Bottomley C, Kleinschmidt I, et al. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia. 2010 May;51(5):883–890.
  • Fiest KM, Sauro KM, Wiebe S, et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology. 2017 Jan 17;88(3):296–303.
  • Vélez-Ruiz NJ, Pennell PB. Issues for Women with Epilepsy. Neurol Clin. 2016 May;34(2):411–425.
  • Abou-Khalil BW. Update on Antiseizure Medications 2022. Continuum (Minneap Minn). 2022 Apr 1;28(2):500–535.
  • AA V, 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. BMC Med. 2017 May 5;15(1):95.
  • Tomson T, Battino D, Bonizzoni E, et al. Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. Lancet Neurol. 2018 Jun;17(6):530–538.
  • Meador KJ, Cohen MJ, Loring DW, et al. Two-Year-Old Cognitive Outcomes in Children of Pregnant Women With Epilepsy in the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs Study. JAMA Neurol. 2021 Aug 1;78(8):927–936.
  • Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013 Mar;12(3):244–252.
  • Weckesser A, Denny E. Women living with epilepsy, experiences of pregnancy and reproductive health: a review of the literature. Seizure. 2013 Mar;22(2):91–98.
  • Zhao Z, Nelson AR, Betsholtz C, et al. Establishment and Dysfunction of the Blood-Brain Barrier. Cell. 2015 Nov 19;163(5):1064–1078.
  • Burton GJ, Fowden AL. The placenta: a multifaceted, transient organ. Philos Trans R Soc Lond B Biol Sci. 2015 Mar 5;370(1663):20140066.
  • Truchet S, Honvo-Houéto E. Physiology of milk secretion. Best Pract Res Clin Endocrinol Metab. 2017 Aug;31(4):367–384.
  • Wm P. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab. 2012 Nov;32(11):1959–1972.
  • Lin L, Yee SW, Kim RB, et al. SLC transporters as therapeutic targets: emerging opportunities. Nat Rev Drug Discov. 2015 Aug;14(8):543–560.
  • Theodoulou FL, Kerr ID. ABC transporter research: going strong 40 years on. Biochem Soc Trans. 2015 Oct;43(5):1033–1040.
  • Tomson T, Battino D. Teratogenic effects of antiepileptic drugs. Lancet Neurol. 2012 Sep;11(9):803–813.
  • Hernández-Díaz S, Smith CR, Shen A, et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012 May 22;78(21):1692–1699.
  • Morrow J, Russell A, Guthrie E, et al. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):193–198.
  • Bromley RL, Weston J, Marson AG. Maternal Use of Antiepileptic Agents During Pregnancy and Major Congenital Malformations in Children. Jama. 2017 Nov 7;318(17):1700–1701.
  • Lockwood PA, Pauer L, Scavone JM, et al. The Pharmacokinetics of Pregabalin in Breast Milk, Plasma, and Urine of Healthy Postpartum Women. J Hum Lact. 2016 Aug 1;32(3):1–8.
  • Drug Product Database (DPD). HCitDPD. Gabapentin: DPD Approved Drugs; 2018.
  • Ohman I, Vitols S, Tomson T. Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy? Epilepsia. 2005 Oct;46(10):1621–1624.
  • Drisaldi A, Weeda E, Neyens R, et al. Accuracy of Valproic Acid Concentration Correction Based on Serum Albumin. Neurocrit Care. 2019 Apr;30(2):301–306.
  • Zaccara G, Messori A, Moroni F. Clinical pharmacokinetics of valproic acid–1988. Clin Pharmacokinet. 1988 Dec;15(6):367–389.
  • Ben-Menachem E. Pregabalin pharmacology and its relevance to clinical practice. Epilepsia. 2004;45(Suppl 6):13–18.
  • Buvanendran A, Kroin JS, Kari M, et al. Can a single dose of 300 mg of pregabalin reach acute antihyperalgesic levels in the central nervous system? Reg Anesth Pain Med. 2010 Nov-Dec;35(6):535–538.
  • Bockbrader HN, Wesche D, Miller R, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661–669.
  • Fagerberg L, Hallström BM, Oksvold P, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014 Feb;13(2):397–406.
  • Brukner AM, Billington S, Benifla M, et al. Abundance of P-glycoprotein and Breast Cancer Resistance Protein Measured by Targeted Proteomics in Human Epileptogenic Brain Tissue. Mol Pharm. 2021 Jun 7;18(6):2263–2273.
  • Nucera B, Brigo F, Trinka E, et al. Treatment and care of women with epilepsy before, during, and after pregnancy: a practical guide. Ther Adv Neurol Disord. 2022;15:17562864221101687.
  • 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. Lancet Neurol. 2011 Jul;10(7):609–617.
  • Goasdoué K, Miller SM, Colditz PB, et al. Review: the blood-brain barrier; protecting the developing fetal brain. Placenta. 2017;54:111–116.
  • Ek CJ, Wong A, Liddelow SA, et al. Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat. Toxicol Lett. 2010 Aug 1;197(1):51–59.
  • Rambeck B, Uh J, TW M, et al. Comparison of brain extracellular fluid, brain tissue, cerebrospinal fluid, and serum concentrations of antiepileptic drugs measured intraoperatively in patients with intractable epilepsy. Epilepsia. 2006 Apr;47(4):681–694.
  • AM B, Zn S, Dj N, et al. Placental passage of antiepileptic drugs at delivery and neonatal outcomes. Epilepsia. 2017 May;58(5):e82–e86.
  • AK B, KJ M, Karanam A, et al. Antiepileptic Drug Exposure in Infants of Breastfeeding Mothers With Epilepsy. JAMA Neurol. 2020 Apr 1;77(4):441–450.
  • Pienimäki P, Lampela E, Hakkola J, et al. Pharmacokinetics of oxcarbazepine and carbamazepine in human placenta. Epilepsia. 1997 Mar;38(3):309–316.
  • May TW, Brandt C, Helmer R, et al. Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy. Epilepsia. 2015 Jul;56(7):1134–1140.
  • Steen B, Rane A, Lönnerholm G, et al. Phenytoin excretion in human breast milk and plasma levels in nursed infants. Ther Drug Monit. 1982;4(4):331–334.
  • Kumagai N, Seki T, Yamada T, et al. Concentrations of zonisamide in serum, free fraction, mixed saliva and cerebrospinal fluid in epileptic children treated with monotherapy. Jpn J Psychiatry Neurol. 1993 Jun;47(2):291–292.
  • Hovinga CA, Pennell PB. Antiepileptic drug therapy in pregnancy II: fetal and neonatal exposure. Int Rev Neurobiol. 2008;83:241–258.
  • Rives ML, Javitch JA, Wickenden AD. Potentiating SLC transporter activity: emerging drug discovery opportunities. Biochem Pharmacol. 2017 Jul;1(135):1–11.
  • Nigam SK. What do drug transporters really do? Nat Rev Drug Discov. 2015 Jan;14(1):29–44.
  • Liu T, Wang Y, Wang J, et al. DYRK1A inhibitors for disease therapy: current status and perspectives. Eur J Med Chem. 2022 Feb 5;229:114062.
  • Tian X, Angioletti-Uberti S, Battaglia G. On the design of precision nanomedicines. Sci Adv. 2020 Jan;6(4):eaat0919.
  • Dickens D, Owen A, Alfirevic A, et al. Lamotrigine is a substrate for OCT1 in brain endothelial cells. Biochem Pharmacol. 2012 Mar 15;83(6):805–814.
  • Chen EC, Khuri N, Liang X, et al. Discovery of Competitive and Noncompetitive Ligands of the Organic Cation Transporter 1 (OCT1; SLC22A1). J Med Chem. 2017 Apr 13;60(7):2685–2696.
  • Ghosh C, Myers R, O’Connor C, et al. Mol Neurobiol. In: Albensi BC, editor. Cortical Dysplasia in Rats Provokes Neurovascular Alterations, GLUT1 Dysfunction, and Metabolic Disturbances That Are Sustained Post-Seizure Induction. NY. Jan, 2022. p. 27.
  • Lauritzen F, Perez EL, Melillo ER, et al. Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy. Neurobiol Dis. 2012 Jan;45(1):165–176.
  • Lauritzen F, de Lanerolle NC, Lee TS, et al. Monocarboxylate transporter 1 is deficient on microvessels in the human epileptogenic hippocampus. Neurobiol Dis. 2011 Feb;41(2):577–584.
  • Yang L, Lin IH, Ting CT, et al. Modulation of the transport of valproic acid through the blood-brain barrier in rats by the Gastrodia elata extracts. J Ethnopharmacol. 2021 Oct;5(278):114276.
  • Ilyas-Feldmann M, Asselin MC, Wang S, et al. P-glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)-[(11) C]verapamil PET. Epilepsia. 2020 Jul;61(7):1472–1480.
  • Han H, Mann A, Ekstein D, et al. Breaking Bad: the Structure and Function of the Blood-Brain Barrier in Epilepsy. Aaps j. 2017 Jul;19(4):973–988.
  • Lazarowski A, Lubieniecki F, Camarero S, et al. Multidrug resistance proteins in tuberous sclerosis and refractory epilepsy. Pediatr Neurol. 2004 Feb;30(2):102–106.
  • Mathias AA, Hitti J, Unadkat JD. P-glycoprotein and breast cancer resistance protein expression in human placentae of various gestational ages. Am J Physiol Regul Integr Comp Physiol. 2005 Oct;289(4):R963–9.
  • Yeboah D, Sun M, Kingdom J, et al. Expression of breast cancer resistance protein (BCRP/ABCG2) in human placenta throughout gestation and at term before and after labor. Can J Physiol Pharmacol. 2006 Dec;84(12):1251–1258.
  • Alcorn J, Lu X, Moscow JA, et al. Transporter gene expression in lactating and nonlactating human mammary epithelial cells using real-time reverse transcription-polymerase chain reaction. J Pharmacol Exp Ther. 2002 Nov;303(2):487–496.
  • Kwok B, Yamauchi A, Rajesan R, et al. Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A. Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R793–802.
  • Kimura S, Morimoto K, Okamoto H, et al. Development of a human mammary epithelial cell culture model for evaluation of drug transfer into milk. Arch Pharm Res. 2006 May;29(5):424–429.
  • Wang Y, Wang Y, Sun R, et al. The treatment value of IL-1β monoclonal antibody under the targeting location of alpha-methyl-L-tryptophan and superparamagnetic iron oxide nanoparticles in an acute temporal lobe epilepsy model. J Transl Med. 2018 Dec 4;16(1):337.
  • Johnson AC, Hammer ES, Sakkaki S, et al. Inhibition of blood-brain barrier efflux transporters promotes seizure in pregnant rats: role of circulating factors. Brain Behav Immun. 2018 Jan;67:13–23.
  • Morin-Brureau M, Lebrun A, Rousset MC, et al. Epileptiform activity induces vascular remodeling and zonula occludens 1 downregulation in organotypic hippocampal cultures: role of VEGF signaling pathways. J Neurosci. 2011 Jul 20;31(29):10677–10688.
  • Librizzi L, Vila Verde D, Colciaghi F, et al. Peripheral blood mononuclear cell activation sustains seizure activity. Epilepsia. 2021 Jul;62(7):1715–1728.
  • Runtz L, Girard B, Toussenot M, et al. Hepatic and hippocampal cytochrome P450 enzyme overexpression during spontaneous recurrent seizures. Epilepsia. 2018 Jan;59(1):123–134.
  • Li YJ, Wang ZH, Zhang B, et al. Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels. J Neuroinflammation. 2013 Jul 5;10:80.
  • Milesi S, Boussadia B, Plaud C, et al. Redistribution of PDGFRβ cells and NG2DsRed pericytes at the cerebrovasculature after status epilepticus. Neurobiol Dis. 2014;71:151–158.
  • Ivens S, Kaufer D, Flores LP, et al. TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain. 2007 Feb;130(Pt 2):535–547.
  • Thomas SV, Jose M, Divakaran S, et al. Malformation risk of antiepileptic drug exposure during pregnancy in women with epilepsy: results from a pregnancy registry in South India. Epilepsia. 2017 Feb;58(2):274–281.
  • Han L, Jiang C. Evolution of blood-brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies. Acta Pharm Sin B. 2021 Aug;11(8):2306–2325.
  • Gao H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharm Sin B. 2016 Jul;6(4):268–286.
  • Ahmadimoghaddam D, Zemankova L, Nachtigal P, et al. Organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter in the placenta and fetal tissues: expression profile and fetus protective role at different stages of gestation. Biol Reprod. 2013 Mar;88(3):55.
  • Nozohouri S, Noorani B, Al-Ahmad A, et al. Estimating Brain Permeability Using In Vitro Blood-Brain Barrier Models. Methods Mol Biol. 2021;2367:47–72.
  • Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017 Jan;114(1):184–194.
  • Oddo A, Peng B, Tong Z, et al. Advances in Microfluidic Blood-Brain Barrier (BBB) Models. Trends Biotechnol. 2019 Dec;37(12):1295–1314.
  • Vatine GD, Barrile R, Workman MJ, et al. Human iPSC-Derived Blood-Brain Barrier Chips Enable Disease Modeling and Personalized Medicine Applications. Cell Stem Cell. 2019 Jun 6;24(6):995–1005.e6.
  • Park TE, Mustafaoglu N, Herland A, et al. Hypoxia-enhanced Blood-Brain Barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies. Nat Commun. 2019 Jun 13;10(1):2621.
  • Blundell C, Yi YS, Ma L, et al. Placental Drug Transport-on-a-Chip: a Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier. In:Goebel U, editor. Adv Healthc Mater. Hoboken, NJ. Vol. 7. 2018 Jan. p. 2.
  • Yin F, Zhu Y, Zhang M, et al. A 3D human placenta-on-a-chip model to probe nanoparticle exposure at the placental barrier. Toxicol In Vitro. 2019;54:105–113.
  • Song K, Zu X, Du Z, et al. Diversity Models and Applications of 3D Breast Tumor-on-a-Chip. Micromachines (Basel). 2021 12;12(7):Jul.
  • Subia B, Dahiya UR, Mishra S, et al. Breast tumor-on-chip models: from disease modeling to personalized drug screening. J Control Release. 2021 Mar;10(331):103–120.
  • Mark D, Haeberle S, Roth G, et al. Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. Chem Soc Rev. 2010 Mar;39(3):1153–1182.
  • Wang X, Qi B, Su H, et al. Pyrilamine-sensitive proton-coupled organic cation (H(+)/OC) antiporter for brain-specific drug delivery. J Control Release. 2017 May;28(254):34–43.
  • Charalambous M, Volk HA, Tipold A, et al. Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: a multi-center randomized parallel group clinical study. J Vet Intern Med. 2019 Nov;33(6):2709–2717.
  • von Blomberg A, Kay L, Knake S, et al. Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring. CNS Drugs. 2020 May;34(5):545–553.
  • Segal EB, Tarquinio D, Miller I, et al. Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: an interim subgroup analysis from a phase 3, long-term, open-label safety study. Epilepsia. 2021 Jun;62(6):1442–1450.
  • Achar A, Myers R, Ghosh C. Drug Delivery Challenges in Brain Disorders across the Blood-Brain Barrier: novel Methods and Future Considerations for Improved Therapy. Biomedicines. 2021 4;9(12):Dec.
  • Wang Z, Zhang C, Huang F, et al. Breakthrough of ZrO(2) nanoparticles into fetal brains depends on developmental stage of maternal placental barrier and fetal blood-brain-barrier. J Hazard Mater. 2021 Jan 15;402:123563.
  • Kuze K, Graves P, Leahy A, et al. Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519–1524.
  • Geddes JR, Gardiner A, Rendell J, et al. Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): a 2 × 2 factorial randomised trial. Lancet Psychiatry. 2016 Jan;3(1):31–39.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.