Effects of Antiepileptic Monotherapy with Clobazam, Phenobarbital, Carbamazepine, and Levetiracetam on Thyroid Hormone Profiles in Children Aged 2–16 Years

Document Type : original article

Authors

1 Department of Pediatrics, School of Medicine, Bu'ali Hospital, Ardabil University of Medical Sciences, Ardabil, Iran.

2 Department of Community Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Abstract

Background: Antiepileptic drugs (AEDs) constitute the cornerstone of epilepsy management in children. However, accumulating evidence suggests that certain AEDs may alter endocrine function, particularly the hypothalamic–pituitary–thyroid axis. Given the critical role of thyroid hormones in growth and neurodevelopment, clarifying the endocrine safety profile of these agents in pediatric populations is clinically essential.
Objective: To evaluate the effects of carbamazepine, phenobarbital, clobazam, and levetiracetam on serum thyroid hormone levels (TSH, FT4, and T3) in children aged 2–16 years over a 6-month treatment period.
Methods: In this prospective before-and-after interventional study, 80 children with epilepsy receiving monotherapy (20 per drug group) were enrolled. Baseline demographic and anthropometric characteristics were comparable across groups. Serum TSH, FT4, and T3 levels, along with weight and height, were measured at treatment initiation and after 6 months. Within-group changes were analyzed using paired t tests, and between-group differences were assessed using one-way analysis of variance (ANOVA). Statistical significance was defined as P < 0.05.
Results: After 6 months, significant alterations in FT4 and T3 levels were observed exclusively in the carbamazepine group (P < 0.05), with mean hormonal changes differing significantly from those in the other treatment groups. No significant thyroid hormone changes were detected in the phenobarbital, clobazam, or levetiracetam groups. Although weight and height increased significantly in all groups (P < 0.01), the magnitude of growth changes did not differ between treatments.
Conclusion: Carbamazepine was associated with measurable alterations in thyroid hormone levels over 6-month, whereas phenobarbital, clobazam, and levetiracetam demonstrated relative short-term endocrine stability. Ongoing thyroid function monitoring may be warranted, particularly in children receiving conventional enzyme-inducing AEDs.

Keywords

References

  1. Li J, Liu T, Liu C, Deng J, Wu S, Kuang S, et al. Treatment of pediatric epilepsy. Pediatric Investigation. 2026.
  2. Cai AJ, Gao K, Zhang F, Jiang YW. Recent advances and current status of gene therapy for epilepsy. World Journal of Pediatrics. 2024 Nov;20(11):1115-37.
  3. Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):522-30.
  4. Vohr BR, Poggi Davis E, Wanke CA, Krebs NF. Neurodevelopment: the impact of nutrition and inflammation during preconception and pregnancy in low-resource settings. Pediatrics. 2017 Apr 1;139(Supplement_1):S38-49.
  5. Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic disorders. 2015 Jun;17(2):117-23.
  6. Kim YS, Kim MS, Park S, Smith L, Radua J, Oh SS, et al. Global, regional and national burden of epilepsy in children and adolescents, 1990–2021: A systematic analysis for the Global Burden of Disease Study 2021. European journal of clinical investigation. 2026 Jan;56(1):e70139.
  7. Pakdaman H, Harandi AA, Gharagozli K, Alaeddini F, Esfandani A, Mirbehbahani SH, et al. Epilepsy lifetime prevalence in Iran: a large population-based national survey. Scientific Reports. 2021 May 3;11(1):9437.
  8. Ravat SH, Gupta R. Antiepileptic drugs in pediatric epilepsy. Journal of Pediatric Neurosciences. 2008 Jan 1;3(1):7-15.
  9. Rosati A, De Masi S, Guerrini R. Antiepileptic drug treatment in children with epilepsy. CNS drugs. 2015 Oct;29(10):847-63.
  10. Han Y, Yang J, Zhong R, Guo X, Cai M, Lin W. Side effects of long-term oral anti-seizure drugs on thyroid hormones in patients with epilepsy: a systematic review and network meta-analysis. Neurological sciences. 2022 Sep;43(9):5217-27.
  11. Zimmermann MB. The importance of adequate iodine during pregnancy and infancy. World Rev Nutr Diet. 2016 May 19;115(10):118-24.
  12. Kim SH, Chung HR, Kim SH, Kim H, Lim BC, Chae JH, et al. Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy. Neuropediatrics. 2012 Jun;43(03):135-9.
  13. Elshorbagy HH, Barseem NF, Suliman HA, Talaat E, AlSHOKARY AH, Abdelghani WE, et al. The impact of antiepileptic drugs on thyroid function in children with epilepsy: new versus old. Iranian Journal of Child Neurology. 2020;14(1):31.
  14. Hamed SA. The effect of antiepileptic drugs on thyroid hormonal function: causes and implications. Expert review of clinical pharmacology. 2015 Nov 2;8(6):741-50.
  15. Attilakos A, Dinopoulos A, Tsirouda M, Paschalidou M, Prasouli A, Stamati A, et al. Effect of levetiracetam monotherapy on lipid profiles and thyroid hormones in children with epilepsy: a prospective study. Epilepsy research. 2019 Sep 1;155:106162.
  16. Yılmaz Ü, Yılmaz TS, Akıncı G, Korkmaz HA, Tekgül H. The effect of antiepileptic drugs on thyroid function in children. Seizure. 2014 Jan 1;23(1):29-35.
  17. Mohankumar S, Rameshkumar R, Selvan T, Nandeesha H, Cg D. A Prospective Cohort Study on the Effect of Antiseizure Medications on Thyroid Function in Children Aged 6 Months to 12 Years with Epilepsy. Sultan Qaboos University Medical Journal. 2024 Nov 27;24(4):528.
  18. El-Farahaty RM, El-Mitwalli A, Azzam H, Wasel Y, Elrakhawy MM, Hasaneen BM. Atherosclerotic effects of long-term old and new antiepileptic drugs monotherapy: a cross-sectional comparative study. Journal of child neurology. 2015 Mar;30(4):451-7.
  19. Güngör O, Özkaya AK, Temiz F. The effect of antiepileptic drugs on thyroid hormonal function: valproic acid and phenobarbital. Acta Neurologica Belgica. 2020 Jun;120(3):615-9.
  20. Cansu A, Serdaroğlu A, Camurdan O, Hırfanoğlu T, Bideci A, Gücüyener K. The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short‐term administration of oxcarbazepine and valproate. Epilepsia. 2006 Nov;47(11):1855-9.
  21. Zhang YX, Shen CH, Lai QL, Fang GL, Ming WJ, Lu RY, et al. Effects of antiepileptic drug on thyroid hormones in patients with epilepsy: a meta-analysis. Seizure. 2016 Feb 1;35:72-9.
  22. Aygün F, Ekici B, Aydınlı N, Aydın BK, Baş F, Tatlı B. Thyroid hormones in children on antiepileptic therapy. International Journal of Neuroscience. 2012 Jan 1;122(2):69-73.
  23. Bidabadi E, Zarkesh M, Mirzaiichaghakabudi M. Thyroid Hormone Levels in Preterm Neonates with Birth Weight Less than 2500 g, Treated with Phenobarbital. Iranian Journal of Child Neurology. 2023 Oct 26;17(4):155.
  24. Cayir A, Turan  MI,  Esin  IS.  An  Examination  of  the  Effects  of  Phenobarbital  on  Thyroid  Function  Tests  in  Childhood  Epilepsy.  HK  J  Paediatr (new series). 2014;19(2):71-4.
  25. Li Y, Kumazawa T, Ishiguro T, Kawakami Y, Nishitani H, Tagawa Y, et al. Hypothyroidism caused by phenobarbital affects patterns of estrous cyclicity in rats. Congenital Anomalies. 2011 Jun;51(2):55-61.
  26. Seymen G, Kutlubay BI. Effects of levetiracetam monotherapy on thyroid function in pediatric epilepsy patients. Northern Clinics of Istanbul. 2025 Dec 29:707.
  27. Isojärvi JI, Turkka J, Pakarinen AJ, Kotila M, Rättyä J, Myllylä VV. Thyroid function in men taking carbamazepine, oxcarbazepine, or valproate for epilepsy. Epilepsia. 2001 Jul 7;42(7):930-4.
  28. Tiihonen M, Liewendahl K, Waltimo O, Ojala M, Välimäki M. Thyroid status of patients receiving long‐term anticonvulsant therapy assessed by peripheral parameters: a placebo‐controlled thyroxine therapy trial. Epilepsia. 1995 Nov;36(11):1118-25.
  29. Verrotti A, Laus M, Scardapane A, Franzoni E, Chiarelli F. Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate. European journal of endocrinology. 2009 Jan;160(1):81-6.
  30. Lossius MI, Taubøll E, Mowinckel P, Gjerstad L. Reversible effects of antiepileptic drugs on thyroid hormones in men and women with epilepsy: a prospective randomized double-blind withdrawal study. Epilepsy & Behavior. 2009 Sep 1;16(1):64-8.
  31. Shih FY, Chuang YC, Chuang MJ, Lu YT, Tsai WC, Fu TY, et al. Effects of antiepileptic drugs on thyroid hormone function in epilepsy patients. Seizure. 2017 May 1;48:7-10.
  32. Güngör O, Yüzbaşı BK, Özhan B, Orhan O, Şevik R, Güngör G. Effects of valproic acid, levetiracetam, carbamazepine, and oxcarbazepine on thyroid function tests in children. Revista da Associação Médica Brasileira. 2024 Dec 16;70(12):e20241177.
  33. Benedetti MS, Whomsley R, Baltes E, Tonner F. Alteration of thyroid hormone homeostasis by antiepileptic drugs in humans: involvement of glucuronosyltransferase induction. European journal of clinical pharmacology. 2005 Dec;61(12):863-72.
Journal of Pediatric Perspectives
Volume 14, Issue 4
April 2026
Pages 20051-20060

Files

Share

How to cite

Statistics