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Growth-related effects of antiseizure medications are of concern in children with epilepsy

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Abstract

Epilepsy is a common chronic neurological condition in children that is treated with antiseizure medications as first-line (and subsequent-line) therapy. Sometimes the underlying cause of epilepsy can be associated with aberrant growth. Antiseizure medications can also increase or decrease the appetite, weight and growth in children with epilepsy. If an antiseizure medication is suspected of impacting appetite and growth, options include dose reduction, switching to another antiseizure medication and adding supportive options. However, these should be considered after weighing the benefits versus the risks of intervention.

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References

  1. Centers for Disease Control and Prevention. Epilepsy fast facts. 2020. https://www.cdc.gov/epilepsy/about/fast-facts.htm. Accessed 30 Nov 2022.

  2. Aaberg KM, Gunnes N, Bakken IJ, et al. Incidence and prevalence of childhood epilepsy: a nationwide cohort study. Pediatrics. 2017;139(5): e20163908.

    Article  PubMed  Google Scholar 

  3. Buraniqi E, Dabaja H, Wirrell EC. Impact of antiseizure medications on appetite and weight in children. Paediatr Drugs. 2022;24(4):335–63.

    Article  PubMed  Google Scholar 

  4. Genetic and rare diseases information center. Dravet syndrome. 2021. https://rarediseases.info.nih.gov/diseases/10430/dravet-syndrome. Accessed 30 Nov 2022.

  5. Eschbach K, Scarbro S, Juarez-Colunga E, et al. Growth and endocrine function in children with Dravet syndrome. Seizure. 2017;52:117–22.

    Article  PubMed  Google Scholar 

  6. Nicita F, Ruggieri M, Polizzi A, et al. Seizures and epilepsy in Sotos syndrome: analysis of 19 Caucasian patients with long-term follow-up. Epilepsia. 2012;53(6):e102–5.

    Article  PubMed  Google Scholar 

  7. Pressler RM, Lagae L. Why we urgently need improved seizure and epilepsy therapies for children and neonates. Neuropharmacology. 2020;170: 107854.

    Article  CAS  PubMed  Google Scholar 

  8. Sondhi V, Sharma S. Non-pharmacological and non-surgical treatment of refractory childhood epilepsy. Indian J Pediatr. 2020;87(12):1062–9.

    Article  PubMed  Google Scholar 

  9. Manitpisitkul P, Shalayda K, Todd M, et al. Pharmacokinetics and safety of adjunctive topiramate in infants (1–24 months) with refractory partial-onset seizures: a randomized, multicenter, open-label phase 1 study. Epilepsia. 2013;54(1):156–64.

    Article  CAS  PubMed  Google Scholar 

  10. Sachdeo RC, Glauser TA, Ritter F, et al. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL Study Group. Neurology. 1999;52(9):1882–7.

    Article  CAS  PubMed  Google Scholar 

  11. Glauser TA, Levisohn PM, Ritter F, et al. Topiramate in Lennox-Gastaut syndrome: open-label treatment of patients completing a randomized controlled trial. Topiramate YL Study Group. Epilepsia. 2000;41:86–90.

    Article  CAS  PubMed  Google Scholar 

  12. Shinnar S, Pellock JM, Conry JA. Open-label, long-term safety study of zonisamide administered to children and adolescents with epilepsy. Eur J Paediatr Neurol. 2009;13(1):3–9.

    Article  PubMed  Google Scholar 

  13. Canger R, Vignoli A, Bonardi R, et al. Felbamate in refractory partial epilepsy. Epilepsy Res. 1999;34(1):43–8.

    Article  CAS  PubMed  Google Scholar 

  14. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group. Epilepsia. 1999;40(8):1147–54.

    Article  CAS  PubMed  Google Scholar 

  15. Appleton R, Fichtner K, LaMoreaux L, et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 24-week, multicentre, open-label study. Dev Med Child Neurol. 2001;43(4):269–73.

    Article  CAS  PubMed  Google Scholar 

  16. Lagae L, Sullivan J, Knupp K, et al. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial. Lancet. 2019;394(10216):2243–54.

    Article  CAS  PubMed  Google Scholar 

  17. Nabbout R, Mistry A, Zuberi S, et al. Fenfluramine for treatment-resistant seizures in patients with dravet syndrome receiving stiripentol-inclusive regimens: a randomized clinical trial. JAMA Neurol. 2020;77(3):300–8.

    Article  PubMed  Google Scholar 

  18. Gil-Nagel A, Sullivan J, Ceulemans B, et al. Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth. Epilepsy Behav. 2021;122: 108212.

    Article  PubMed  Google Scholar 

  19. Arroyo S, Dodson WE, Privitera MD, et al. Randomized dose-controlled study of topiramate as first-line therapy in epilepsy. Acta Neurol Scand. 2005;112(4):214–22.

    Article  CAS  PubMed  Google Scholar 

  20. Glauser TA, Dlugos DJ, Dodson WE, et al. Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents. J Child Neurol. 2007;22(6):693–9.

    Article  PubMed  Google Scholar 

  21. Elterman RD, Glauser TA, Wyllie E, et al. A double-blind, randomized trial of topiramate as adjunctive therapy for partial-onset seizures in children. Topiramate YP Study Group. Neurology. 1999;52(7):1338–44.

    Article  CAS  PubMed  Google Scholar 

  22. Faught E, Ayala R, Montouris GG, et al. Randomized controlled trial of zonisamide for the treatment of refractory partial-onset seizures. Neurology. 2001;57(10):1774–9.

    Article  CAS  PubMed  Google Scholar 

  23. Guerrini R, Rosati A, Segieth J, et al. A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy. Epilepsia. 2013;54(8):1473–80.

    Article  CAS  PubMed  Google Scholar 

  24. Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut Syndrome). N Engl J Med. 1993;328(1):29–33.

    Article  Google Scholar 

  25. Bergen DC, Ristanovic RK, Waicosky KKA, Hoeppner TJ. Weight loss in patients taking felbamate. Clin Neuropharmacol. 1995;18(1):23–7.

    Article  CAS  PubMed  Google Scholar 

  26. Arzimanoglou A, Ferreira JA, Satlin A, et al. Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: an interim analysis from a multicenter, randomized, active-controlled, open-label study. Eur J Paediatr Neurol. 2016;20(3):393–402.

    Article  PubMed  Google Scholar 

  27. Arzimanoglou A, Ferreira J, Satlin A, et al. Evaluation of long-term safety, tolerability, and behavioral outcomes with adjunctive rufinamide in pediatric patients (>/=1 to <4 years old) with Lennox-Gastaut syndrome: final results from randomized study 303. Eur J Paediatr Neurol. 2019;23(1):126–35.

    Article  PubMed  Google Scholar 

  28. Ohtsuka Y, Yoshinaga H, Shirasaka Y, et al. Long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome receiving adjunctive rufinamide therapy: an open-label study following a randomized clinical trial. Epilepsy Res. 2016;121:1–7.

    Article  CAS  PubMed  Google Scholar 

  29. Chiron C, Marchand MC, Tran A, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group Lancet. 2000;356(9242):1638–42.

    CAS  Google Scholar 

  30. Miller I, Scheffer IE, Gunning B, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in dravet syndrome: a randomized clinical trial. JAMA Neurol. 2020;77(5):613–21.

    Article  PubMed  Google Scholar 

  31. Patel AD, Mazurkiewicz-Beldzinska M, Chin RF, et al. Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: results of a long-term open-label extension trial. Epilepsia. 2021;62(9):2228–39.

    Article  CAS  PubMed  Google Scholar 

  32. Liu E, Dilley D, McDonough B, et al. Safety and tolerability of adjunctive brivaracetam in pediatric patients < 16 years with epilepsy: an open-label trial. Paediatr Drugs. 2019;21(4):291–301.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013;54(1):141–55.

    Article  CAS  PubMed  Google Scholar 

  35. Verity CM, Hosking G, Easter DJ. A multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. The Paediatric EPITEG Collaborative Group. Dev Med Child Neurol. 1995;37(2):97–108.

    Article  CAS  PubMed  Google Scholar 

  36. Biton V, Mirza W, Montouris G, et al. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology. 2001;56(2):172–7.

    Article  CAS  PubMed  Google Scholar 

  37. Mann D, Antinew J, Knapp L, et al. Pregabalin adjunctive therapy for focal onset seizures in children 1 month to <4 years of age: a double-blind, placebo-controlled, video-electroencephalographic trial. Epilepsia. 2020;61(4):617–26.

    Article  CAS  PubMed  Google Scholar 

  38. Piña-Garza JE, Rosenfeld W, Saeki K, et al. Efficacy and safety of adjunctive perampanel in adolescent patients with epilepsy: post hoc analysis of six randomized studies. Epilepsy Behav. 2020;104(Pt A): 106876.

    Article  PubMed  Google Scholar 

  39. Lagae L, Villanueva V, Meador KJ, et al. Adjunctive perampanel in adolescents with inadequately controlled partial-onset seizures: a randomized study evaluating behavior, efficacy, and safety. Epilepsia. 2016;57(7):1120–9.

    Article  CAS  PubMed  Google Scholar 

  40. Rosenfeld W, Conry J, Lagae L, et al. Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. Eur J Paediatr Neurol. 2015;19(4):435–45.

    Article  PubMed  Google Scholar 

  41. Chadwick D. Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study Vigabatrin European Monotherapy Study Group. Lancet. 1999;354(9172):13–9.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Arnold Lee.

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E. S. Kim, a contracted employee of Adis International Ltd/Springer Nature, and A. Lee, a salaried employee of Adis International Ltd/Springer Nature, declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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Kim, E.S., Lee, A. Growth-related effects of antiseizure medications are of concern in children with epilepsy. Drugs Ther Perspect 39, 96–101 (2023). https://doi.org/10.1007/s40267-023-00981-7

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