The impact of antiepileptic drug therapy on oral health in children with epilepsy: current evidence, mechanisms, and management strategies

Elżbieta Sołowiej; Weronika Sołowiej; Kamilla Blecharz-Klin

doi:10.56782/pps.809

Published : 2025-11-30

Vol. 24 No. 2 (2026)

The impact of antiepileptic drug therapy on oral health in children with epilepsy: current evidence, mechanisms, and management strategies

Elżbieta Sołowiej

Weronika Sołowiej

Kamilla Blecharz-Klin

DOI: https://doi.org/10.56782/pps.809

Abstract

Epilepsy represents one of the most common chronic neurological disorders worldwide, with approximately half of all cases diagnosed during childhood or adolescence. Although the condition remains incurable, effective seizure control can be achieved in up to 70% of patients through appropriately selected antiepileptic drugs (AEDs), administered as monotherapy or in combination. Despite their therapeutic efficacy, AEDs are associated with a range of adverse effects, including those affecting oral health, which may substantially impair patients’ quality of life. This review summarizes current evidence regarding the impact of AED therapy on oral health in children with epilepsy and discusses potential pathophysiological mechanisms underlying these adverse effects. A comprehensive literature search was performed in the PubMed and Google Scholar databases using the free-text terms and Medical Subject Headings (MeSH), such as “Epilepsy/drug therapy” and “Anticonvulsants/adverse effects” and the following keywords: “antiepileptic drugs & side effects,” “antiepileptic drugs & oral health status in children,” “oral side effects,” “antiepileptic drugs,” as well as relevant synonyms such as “antiseizure medications,” “AEDs,” and “anticonvulsants.” The review includes data from systematic reviews, meta-analyses, and original research conducted in Europe and globally. Reported oral manifestations associated with AED use include gingival overgrowth, gingivitis, xerostomia, and glossitis, particularly linked to first-generation agents such as phenytoin and valproic acid. Pediatric patients undergoing long-term AED therapy demonstrate increased susceptibility to dental caries, periodontal disease, tooth loss, and maxillofacial bone demineralization, which may elevate the risk of fractures following trauma. Further studies are warranted to elucidate the oral health implications of newer-generation AEDs and to clarify the molecular mechanisms responsible for these complications. Given the chronic nature of epilepsy and the cumulative impact of long-term pharmacotherapy, children receiving AEDs require individualized preventive strategies, emphasizing meticulous oral hygiene and regular dental monitoring to reduce the risk of treatment-related oral pathology.

Keywords:

AEDs, antiepileptic drugs, anticonvulsants adverse effects, oral health, gingival overgrowth

Similar Articles

Anna Dominiczak, Agata Janczak, Martyna Wołek, Katarzyna Mazurek, Maciej Bara, Proton pump inhibitors: prolonged intake and adverse effects , Prospects in Pharmaceutical Sciences: Vol. 22 No. 4 (2024)
Agnieszka Sienicka, Krzysztof Kubasik, Agata Pisula, The glucagon-like peptide-1 analogues therapy in the non-diabetic patients , Prospects in Pharmaceutical Sciences: Vol. 21 No. 1 (2023)
Paula Abola, George Jabishvili, Incidence of adverse and safety events in individuals with Parkinson’s disease treated with catechol-o-methyltransferase inhibitor opicapone as an add-on to levodopa treatment: a systematic review and meta-analysis , Prospects in Pharmaceutical Sciences: Vol. 23 No. 4 (2025)
Paulina Brewczyńska, Justyna Makowska, Dorota Skrajnowska, Marta Teryks, Andrzej Tokarz, ADDICTION TO CONVENTIONAL AND ELECTRONIC CIGARETTES AND THE RISKS OF PHARMACOTHERAPY IN SMOKERS. , Prospects in Pharmaceutical Sciences: Vol. 13 No. 3 (2015)
Paulina Oleksa, Daria Żuraw, Kacper Jasiński, Mateusz Sobczyk, Mikołaj Porzak, Alicja Sodolska, Karolina Haczkur-Pawłowska, Drugs and other chemical substances inducing diabetes – review of the literature , Prospects in Pharmaceutical Sciences: Vol. 22 No. 2 (2024)
Aleksandra Białczyk, Gabriela Leśniak, Filip Nadolny, Justyna Mrowiec, Antoni Otałęga, Exploring digital health horizons: a narrative review of e-health innovations in Poland, Spain, Romania and Estonia. , Prospects in Pharmaceutical Sciences: Vol. 22 No. 1 (2024)
Yunus Emre Kahraman, Yılmaz Çalışkan, A financial perspective on the pharmaceutical industry , Prospects in Pharmaceutical Sciences: Vol. 22 No. 1 (2024)
Dominika Winiarz, Kamila Domańska, Kinga Paluch, Dorota Dorota Skrajnowska, PROBIOTICS AND HEALTH - TODAY AND TOMORROW , Prospects in Pharmaceutical Sciences: Vol. 15 No. 10 (2017)
Aneta Emilia Jabłońska, Krzysztof Adam Stępień, COUNTERFEITING OF MEDICINAL PRODUCTS AND THREATS ASSOCIATED WITH THEIR TAKING , Prospects in Pharmaceutical Sciences: Vol. 17 No. 11 (2019)
Agnieszka Kalicka, Natalia Tarłowska, Counterfeit and illegal medicinal products as an example of drugs that do not meet the basic quality requirements , Prospects in Pharmaceutical Sciences: Vol. 21 No. 4 (2023)

1 2 3 4 5 6 7 8 9 10 > >>

You may also start an advanced similarity search for this article.

Details

References

Statistics

Authors

Download files

PDF

Citation rules

Sołowiej, E., Sołowiej, W., & Blecharz-Klin, K. (2025). The impact of antiepileptic drug therapy on oral health in children with epilepsy: current evidence, mechanisms, and management strategies. Prospects in Pharmaceutical Sciences, 24(2), 67–78. https://doi.org/10.56782/pps.809

Altmetric indicators

Cited by / Share

Licence

This work is licensed under a Creative Commons Attribution 4.0 International License.

References

1. Cowan; L.D. The epidemiology of the epilepsies in children. Ment. Retard. Dev. Disabil. Res. Rev. 2002, 8(3), 171-181. DOI: 10.1002/mrdd.10035

2. Beniczky, S.; Trinka, E.; Wirrell, E.; Abdulla, F.; Al Baradie, R.; Alonso Vanegas, M.; Auvin, S.; Singh, M.B.; Blumenfeld, H.; Bogacz Fressola, A.; Caraballo, R.; Carreño, M.; Cendes, F.; Charway, A.; Cook; M.; Craiu, D.; Ezeala-Adikaibe, B.; Frauscher, B.; French, J.; Gule, M.V.; Higurashi, N.; Ikeda, A.; Jansen, F.E.; Jobst, B.; Kahane, P.; Kishk, N.; Khoo, C.S.; Vinayan, K.P.; Lagae, L.; Lim, K.S.; Lizcano, A.; McGonigal, A.; Pérez-Gosiengfiao, K.T.; Ryvlin, P.; Specchio, N.; Sperling, M.R.; Stefan, H.; Tatum, W.; Tripathi, M.; Yacubian, E.M.; Wiebe, S.; Wilmshurst, J.; Zhou, D.; Cross, J.H. Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy. Epilepsia 2025, 66(6), 1804–1823. DOI: 10.1111/epi.18338

3. Specchio, N.; Wirrell, E.C.; Scheffer, I.E.; Nabbout, R.; Riney, K.; Samia, P.; Guerreiro, M.; Gwer, S.; Zuberi, S.M.; Wilmshurst, J.M.; Yozawitz, E.; Pressler, R.; Hirsch, E.; Wiebe, S.; Cross, H.J.; Perucca, E.; Moshé, S.L.; Tinuper, P. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022, 63(6), 1398-1442. DOI: 10.1111/epi.17241

4. Wirrell, E. Infantile, Childhood, and Adolescent Epilepsies. Continuum (Minneap Minn). 2016, 22(1 Epilepsy), 60-93. DOI: 10.1212/CON.0000000000000269

5. Gogou, M.; Cross, J.H. Seizures and Epilepsy in Childhood. Continuum (Minneap Minn). 2022, 28(2), 428-456. DOI: 10.1212/CON.0000000000001087

6. Zuberi, S.M.; Wirrell, E.; Yozawitz, E.; Wilmshurst, J.M.; Specchio, N.; Riney, K.; Pressler, R.; Auvin, S.; Samia, P.; Hirsch, E.; Galicchio, S.; Triki, C.; Snead, O.C.; Wiebe, S.; Cross, J.H.; Tinuper, P.; Scheffer, I.E.; Perucca, E.; Moshé, S.L.; Nabbout, R. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022, 63(6), 1349–1397. DOI: 10.1111/epi.17239

7. Riney, K.; Bogacz, A.; Somerville, E.; Hirsch, E.; Nabbout, R.; Scheffer, I.E.; Zuberi, S.M.; Alsaadi, T.; Jain, S.; French, J.; Specchio, N.; Trinka, E.; Wiebe, S.; Auvin, S.; Cabral-Lim, L.; Naidoo, A.; Perucca, E.; Moshé, S.L.; Wirrell, E.C.; Tinuper, P. International League Against Epilepsy classification and definition of epilepsy syndromes with onset at a variable age: position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia 2022, 63(6), 1443–1474. DOI: 10.1111/epi.17240

8. Covanis, A. Panayiotopoulos syndrome: a benign childhood autonomic epilepsy frequently imitating encephalitis, syncope, migraine, sleep disorder, or gastroenteritis. Pediatrics 2006, 118(4), e1237-e1243. DOI: 10.1542/‌peds.2006-0623

9. Shinnar, S.; Pellock, J.M. Update on the epidemiology and prognosis of paediatric epilepsy. J. Child Neurol. 2002, 17 Suppl 1, 4–17. DOI: 10.1177/08830738020170010201

10. Kumar, G. Evaluation and management of drug resistant epilepsy in children. Curr. Probl. Pediatr. Adolesc. Health Care 2021, 51(7), Art. No: 101035. DOI: 10.1016/j.cppeds.2021.101035

11. Karacabey, B.N.; Pembegül Yıldız, E.; Çalışkan, M. Çocuklarda Antiepileptik İlaçlar. Çocuk Dergisi. 2022, 22(2), 117-123. DOI: 10.26650/jchild.2022.837819

12. Pons, G. Side effects of antiepileptic drugs in children. Bratisl. Lék. Listy 1991, 92(12), 586-588.

13. D’Onofrio, G.; Roberti, R.; Riva, A.; Russo, E.; Verrotti, A.; Striano, P.; Belcastro, V. Pharmacodynamic rationale for the choice of antiseizure medications in the paediatric population. Neurotherapeutics 2024, 21(3), Art. No: e00344. DOI: 10.1016/j.neurot.2024.e00344

14. Liu, Y.; Wang, Y.; Li, X.; Wu, X. Efficacy and safety of levetiracetam vs. oxcarbazepine in the treatment of children with epilepsy: a systematic review and meta-analysis. Front. Pediatr. 2024, 12, Art. No: 1336744. DOI: 10.3389/fped.2024.1336744

15. Latif, Z.; Mukhtar, M.; Rohan, A.; Shah, W.F.; Aslam, Z.; Akbar, M.; Raza, H.M.Z. Comparison of Levetiracetam Versus Sodium Valproate as a Monotherapy in Early Childhood Epilepsy. Cureus 2025, 17(7), Art. No: e87574. DOI: 10.7759/cureus.87574

16. Halma, E.; de Louw, A.J.; Klinkenberg, S.; Aldenkamp, A.P.; IJff, D.M.; Majoie, M. Behavioural side-effects of levetiracetam in children with epilepsy: a systematic review. Seizure 2014, 23(9), 685–691. DOI: 10.1016/j.seizure.2014.06.004

17. Sridharan, S.; Nunna, P.; Jaicob, T.E.; Agustine, D.; Shetty, V.; Srirangarajan, D. Role of Epithelial Mesenchymal Transition in Phenytoin Influenced Gingival Overgrowth in Children and Young Adults. A Preliminary Clinical and Immunohistochemical Study. J. Clin. Pediatr. Dent. 2019, 43(5), 350-355. DOI: 10.17796/1053-4625-43.5.9

18. Suneja, B.; Chopra, S.; Thomas, A.M.; Pandian, J. A Clinical Evaluation of Gingival Overgrowth in Children on Antiepileptic Drug Therapy. J. Clin. Diagn. Res. 2016, 10(1), ZC32–ZC36. DOI:10.7860/JCDR/2016/16443.7069

19. Kumar, R.; Singh, R.K.; Verma, N.; Verma, U.P. Phenytoin-induced severe gingival overgrowth in a child. BMJ Case Rep. 2014, 2014, Art. No: bcr2014204046 DOI: 10.1136/bcr-2014-204046

20. Kopciuch, D.; Kus, K.; Fliciński, J.; Steinborn, B.; Winczewska-Wiktor, A.; Paczkowska, A.; Zaprutko, T.; Ratajczak, P.; Nowakowska, E. Pharmacovigilance in pediatric patients with epilepsy using antiepileptic drugs. Int. J. Environ. Res. Public Health 2022, 19(8), Art. No: 4509. DOI: 10.3390/ijerph19084509

21. Ghafoor P.A.; Rafeeq M.; Dubey A. Assessment of oral side effects of Antiepileptic drugs and traumatic oro-facial injuries encountered in Epileptic children. J. Int. Oral Health 2014, 6(2), 126-128.

22. Beaumont, J.; Chesterman, J.; Kellett, M.; Durey, K. Gingival overgrowth: Part 1: aetiology and clinical diagnosis. Br. Dent. J. 2017, 222, 85-91. DOI: 10.1038/sj.bdj.2017.71

23. Dongari-Bagtzoglou, A.; Research, Science and Therapy Committee, American Academy of Periodontology. Drug-associated gingival enlargement. J. Periodontol. 2004, 75(10), 1424-1431. DOI: 10.1902/jop.2004.75.10.1424

24. Thomas, D.C.; Parekh, S.; Jayaraman, S.; Anjum, K.; Naik, V.; Chandrashekar, J.; Pitchumani, P.K. Gingival enlargements: Review of concepts in the context of evolving terminology and implications in clinical dentistry. J. Am. Dent. Assoc. 2025, 156(10), 802–815. DOI: 10.1016/j.adaj.2025.07.012

25. Tungare, S.; Paranjpe, A.G. Drug-Induced Gingival Overgrowth. 2022 Sep 19. In: StatPearls Internet. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30860753

26. Trackman, P.C.; Kantarci, A. Molecular and clinical aspects of drug-induced gingival overgrowth. J. Dent. Res. 2015, 94(4), 540-546. DOI: 10.1177/0022034515571265

27. Kimball, O.P. The treatment of epilepsy with sodium diphenyl hydantoinate. J. Am. Med. Assoc. 1939, 112, 1244-1245. DOI: 10.1001/jama.1939.02800130028009

28. Tan, H.; Gürbüz, T.; Dağsuyu, I.M. Gingival enlargement in children treated with antiepileptics. J. Child Neurol. 2004, 19(12), 958-963. DOI: 10.1177/0883073 8040190120901

29. Majola, M.P.; McFadyen, M.L.; Connolly, C.; Nair, Y.P.; Govender, M.; Laher, M.H. Factors influencing phenytoin-induced gingival enlargement. J. Clin. Periodontol. 2000, 27(7), 506-512. DOI:10.1034/j.1600-051X.2000.027007506.x

30. Casetta, I.; Granieri, E.; Desiderá, M.; Monetti, V.C.; Tola, M.R.; Paolino, E.; Govoni, V.; Calura, G. Phenytoin-induced gingival overgrowth: a community-based cross-sectional study in Ferrara, Italy. Neuroepidemiology 1997, 16(6), 296-303. DOI: 10.1159/000109700

31. Prasad, V.N.; Chawla, H.S.; Goyal, A.; Gauba, K.; Singhi, P. Incidence of phenytoin-induced gingival overgrowth in epileptic children: a six-month evaluation. J. Indian Soc. Pedod. Prev. Dent. 2002, 20(2), 73-80.

32. Dahllöf, G.; Axiö, E.; Modéer, T. Regression of phenytoin-induced gingival overgrowth after withdrawal of medication. Swed. Dent. J. 1991, 15(3), 139-143.

33. Corrêa, J.D.; Queiroz-Junior, C.M.; Costa, J.E.; Teixeira, A.L.; Silva, T.A. Phenytoin-induced gingival overgrowth: a review of the molecular, immune, and inflammatory features. ISRN Dent. 2011, 2011, Art. No: 497850. DOI: 10.5402/2011/497850

34. Gallo, C.; Bonvento, G.; Zagotto, G.; Mucignat-Caretta, C. Gingival overgrowth induced by anticonvulsant drugs: A cross-sectional study on epileptic patients. J. Periodontal Res. 2021, 56(2), 363-369. DOI: 10.1111/jre.12828

35. James, J.; Jose, J.; Gafoor, V.A. Levetiracetam-induced gingival hyperplasia. J. Postgrad. Med. 2022, 68(3), 168-169. DOI: 10.4103/jpgm.jpgm_1059_21

36. Shata, M.O.; Shatla, H.M.; Badawy, S.; Metkees, M.M. Effects of Levetiracetam and Topiramate Monotherapy on Oral Health in Epileptic Children. Egypt. J. Hosp. Med. 2021, 84(1), 2411–2416. DOI: 10.21608/ejhm.2021.184657

37. Kato, T.; Okahashi, N.; Kawai, S.; Kato, T.; Inaba, H.; Morisaki, I.; Amano, A. Impaired degradation of matrix collagen in human gingival fibroblasts by the antiepileptic drug phenytoin. J. Periodontol. 2005, 76(6), 941-950. DOI: 10.1902/jop.2005.76.6.941

38. Kato, T.; Okahashi, N.; Ohno, T.; Inaba, H.; Kawai, S.; Amano, A. Effect of phenytoin on collagen accumulation by human gingival fibroblasts exposed to TNF-alpha in vitro. Oral Dis. 2006, 12(2), 156-162. DOI: 10.1111/j.1601-0825.2005.01175.x

39. Kataoka, M.; Kido, J.; Shinohara, Y.; Nagata, T. Drug-induced gingival overgrowth – a review. Biol. Pharm. Bull. 2005, 28(10), 1817-1821. DOI: 10.1248/bpb.28.1817

40. Hassell, T.M.; Gilbert, G.H. Phenytoin sensitivity of fibroblasts as the basis for susceptibility to gingival enlargement. Am. J. Pathol. 1983, 112(2), 218-223.

41. Deng, Y.T.; Wu, K.J.; Kuo, M.Y. Phenytoin induces connective tissue growth factor (CTGF/CCN2) production through NADPH oxidase 4-mediated latent TGFβ1 activation in human gingiva fibroblasts: Suppression by curcumin. J. Periodontal. Res. 2022, 57(6), 1219-1226. DOI: 10.1111/jre.13058

42. Zorlu, S.; Öner Özdaş, D.; İkikarakayalı, G.; Erdem, A.P.; Sepet, E.; Trosola, Ş.C.; Güven, Y.; Karataban, P.K.; Tatlı, B.; Çalışkan, M.M. The Effect of Valproic Acid Therapy on Dental and Periodontal Health of Children With Epilepsy. Nobel Med. 2017, 13(1), 26-30.

43. Huang, C.; Chu, C.; Peng, Y.; Zhang, N.; Yang, Z.; You, J.; Wei, F. Correlations between gastrointestinal and oral microbiota in children with cerebral palsy and epilepsy. Front Pediatr. 2022, 10, Art. No: 988601. DOI: 10.3389/fped.2022.988601

44. Mielnik-Błaszczak, M.; Skawińska, A.; Michałowski, A.; Błaszczak, J.; Książek, K. The impact of antiepileptic drugs on the condition of the oral cavity in children and youth affected with epilepsy. Pol. J. Public Health 2015, Art. No: 125. DOI: 10.1515/pjph-2015-0035

45. Choo, P.J.; Taing, M-W.; Teoh, L. A retrospective study of drugs associated with xerostomia from the Australian Database of Adverse Event Notifications. Int. J. Pharm. Pract. 2022, 30(6), 548-553. DOI: 10.1093/ijpp/riac051

46. Abed, F.; Al-Jubouri, R. Evaluation of Oral Health Status in Patients Receiving Antiepileptic Medications. J. Baghdad Coll. Dent. 2014, 26, 69-73. DOI: 10.12816/0015198

47. Tian, J.; Zhu, Y.; Gui, J. Oral adverse events associated with antiseizure medications: An analysis of the FDA adverse event reporting system (FAERS) database. Epilepsy Behav. 2025, 171, Art. No: 110619. DOI: 10.1016/j.yebeh.2025.110619

48. Walsh, L.J. Dry mouth: a clinical problem for children and young adults. Int. Dent. SA. 2007, 9(6), 48–58.

49. Fortuna, G.; Whitmire, S.; Sullivan, K.; Alajbeg, I.; Andabak-Rogulj, A.; Pedersen, A.M.L.; Vissink, A.; di Fede, O.; Aria, M.; Jager, D.J.; Noll, J.; Jensen, S.B.; Wolff, A.; Brennan, M.T. Impact of medications on salivary flow rate in patients with xerostomia: a retrospective study by the Xeromeds Consortium. Clin. Oral Investig. 2023, 27(1), 235-248. DOI: 10.1007/s00784-022-04717-1

50. Chiș, I.A.; Andrei, V.; Muntean, A.; Moldovan, M.; Mesaroș, A.Ș.; Dudescu, M.C.; Ilea, A. Salivary Biomarkers of Anti-Epileptic Drugs: A Narrative Review. Diagnostics (Basel) 2023, 13(11), Art. No: 1962. DOI:10.3390/diagnostics13111962

51. Mauz, P.S.; Mörike, K.; Kaiserling, E.; Brosch, S. Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects. Acta Otolaryngol. 2005, 125(4), 386-391. DOI: 10.1080/00016480410024460

52. Farooq, I.; Bugshan, A. The role of salivary contents and modern technologies in the remineralisation of dental enamel: a narrative review. F1000Res. 2020, 9, Art. No: 171. DOI: 10.12688/f1000research.22499.3

53. Pedersen, A.M.L.; Sørensen, C.E.; Proctor, G.B.; Carpenter, G.H.; Ekström, J. Salivary secretion in health and disease. J. Oral Rehabil. 2018, 45(9), 730-746. DOI: 10.1111/joor.12664

54. Baxter-Jones, D.G.; Faulkner, R.A.; Forwood, M.R.; Mirwald, R.L.; Bailey, D.A. Bone mineral accrual from 8 to 30 years of age: An estimation of peak bone mass. J. Bone Miner. Res. 2011, 26(8), 1729–1739. DOI: 10.1002/jbmr.412

55. Zhang, Y.; Zheng, Y.X.; Zhu, J.M.; Zhang, J.M.; Zheng, Z. Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: A meta-analysis. J. Zhejiang Univ. Sci. B 2015, 16, 611–621. DOI: 10.1631/jzus.B1500021

56. Babayigit, A.; Dirik, E.; Bober, E.; Cakmakci, H. Adverse Effects of Antiepileptic Drugs on Bone Mineral Density. Pediatr. Neurol. 2006, 35(3), 177–181. DOI: 10.1016/j.pediatrneurol.2006.03.004

57. Berkvens, J.J.L.; Mergler, S.; Beerhorst, K.; Verschuure, P.; Tan, I.Y.; Majoie, H.J.M.; van den Bergh, J.P.W. Bone mineral density and fractures in institutionalised children with epilepsy and intellectual disability. J. Intellect. Disabil. Res. 2021, 65(11), 962–970. DOI: 10.1111/jir.12880

58. Fabiani, L.; Mosca, G.; Giannini, D.; Giuliani, A.R.; Farello, G.; Marci, M.C.; Ballatori, E. Dental caries and bone mineral density: a cross sectional study. Eur. J. Paediatr. Dent. 2006, 7(2), 67–72.

59. Tumani Üstdal, B.; Soydan Çabuk, D.; Coşgunarslan, A.; Evlice, B.; Evlice, A. Evaluation of the effect of antiepileptic drugs on mandibular bone quality by fractal analysis. Oral Radiol. 2023, 39(3), 563-569. DOI: 10.1007/s11282-023-00671-0

60. Pack, A.M.; Olarte, L.S.; Morrell, M.J.; Flaster, E.; Resor, S.R.; Shane, E. Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav. 2003, 4(2), 169-174. DOI: 10.1016/s1525-5050(03)00036-2.

61. Kumandas, S.; Koklu, E.; Gümüs, H.; Koklu, S.; Kurtoglu, S.; Karakukcu, M.; Keskin, M. Effect of Carbamezapine and Valproic Acid on Bone Mineral Density, IGF-I and IGFBP-3. J. Pediatr. Endocrinol. Metab. 2006, 19(4), 529–534. DOI: 10.1515/jpem-2006-190411

62. Jones, G.; Prosser, D.E.; Kaufmann, M. Cytochrome P450-mediated metabolism of vitamin D. J. Lipid Res. 2014, 55(1), 13-31. DOI: 10.1194/jlr.R031534

63. Feldkamp, J.; Becker, A.; Witte, O.W.; Scharff, D.; Scherbaum, W.A. Long-term anticonvulsant therapy leads to low bone mineral density – evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. Exp. Clin. Endocrinol. Diabetes 2000, 108(1), 37–43. DOI: 10.1055/s-0032-1329213

64. Zhong, R.; Chen, Q.; Zhang, X.; Li, M.; Liang, J.; Lin, W. Bone Mineral Density Loss in People With Epilepsy Taking Valproate as a Monotherapy: A Systematic Review and Meta-Analysis. Front. Neurol. 2019, 10, Art. No: 1171. DOI: 10.3389/fneur.2019.01171

65. Jacobsen, P.E.; Henriksen, T.B.; Haubek, D.; Østergaard, J.R. Prenatal exposure to antiepileptic drugs and dental agenesis. PLoS One 2014, 9(1), Art. No: e84420. DOI:10.1371/journal.pone.0084420

66. Zhuo, L.; Zhang, Y. Effects of new antiseizure medication on bone metabolism and bone mineral density in children: A meta-analysis. Front. Pediatr. 2022, 10, Art. No: 1015691. DOI: 10.3389/fped.2022.1015691

67. Josephson, C.B.; Gonzalez-Izquierdo, A.; Denaxas, S.; Sajobi, T.T.; Klein, K.M.; Wiebe, S. Independent associations of incident epilepsy and enzyme-inducing and non-enzyme-inducing antiseizure medications with the development of osteoporosis. JAMA Neurol. 2023, 80(8), 843-850. DOI: 10.1001/jamaneurol.2023.1580

68. Cornacchio, A.L.; Burneo, J.G.; Aragon, C.E. The effects of antiepileptic drugs on oral health. J. Can. Dent. Assoc. 2011, 7, Art. No: b140.

69. Church, L.F.Jr.; Brandt, S.K. Phenytoin-induced gingival overgrowth resulting in delayed eruption of the primary dentition. A case report. J. Periodontol. 1984, 55(1), 19-21. DOI: 10.1902/jop.1984.55.1.19

70. Girgis, S.S.; Staple, P.H.; Miller, W.A.; Sedransk, N.; Thompson, T. Dental root abnormalities and gingival overgrowth in epileptic patients receiving anticonvulsant therapy. J. Periodontol. 1980, 51(8), 474-482. DOI: 10.1902/jop.1980.51.8.474

71. Arya, R.; Gulati, S.; Kabra, M.; Sahu, J.K.; Kalra, V. Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children. Neurology 2011, 76(15), 1338-1343. DOI: 10.1212/WNL.0b013e3182152844

72. Prasad, V.N.; Chawla, H.S.; Goyal, A.; Gauba, K.; Singhi, P. Folic acid and phenytoin-induced gingival overgrowth – is there a preventive effect. J. Indian Soc. Pedod. Prev. Dent. 2004, 22(2), 82-91.

73. Karn, M.; Sah, R.; Sapkota, S. Phenytoin-induced gingival overgrowth. Clev. Clin. J. Med. 2022, 89(9), 488-489. DOI: 10.3949/ccjm.89a.21107

74. Modéer, T.; Dahllöf, G. Development of phenytoin-induced gingival overgrowth in non-institutionalised epileptic children subjected to different plaque control programmes. Acta Odontol. Scand. 1987, 45(2), 81-85. DOI: 10.3109/00016358709098361

75. Dawar, A.; Gumber, B.; Makker, K. Periodontal Management to Improve Oral Health-related Quality of Life in an Adolescent Girl with Phenytoin-induced Gingival Enlargement: A Case Report. Int. J. Clin. Pediatr. Dent. 2025, 18(5), 599-605. DOI: 10.5005/jp-journals-10005-3133.

76. Balcı, T.; Çakır Biçer, N.; Gazeteci Tekin, H.; Edem, P. Evaluation of the Effect of Parenting Style and Parental Mealtime Actions on the Eating Behavior of Children with Epilepsy. Nutrients 2024, 16(9), Art. No: 1384. DOI: 10.3390/nu16091384

77. Amrollahi, N.; Ghorbani, F.; Chegeni, M. Impact of epilepsy on oral and dental health status in children: a systematic review and meta-analysis. Saudi Dent. J. 2025, 37(7-9), Art. No: 45. DOI:10.1007/s44445-025-00053-8

78. Dogan, M.S.; Yıldız, Ş. Effects of Different Anti-Epileptic Drug Groups and Brushing on the Color Stability of Restorative Materials Used in Pedodontics: An In Vitro Evaluation. Children (Basel) 2024, 11(2), Art. No: 235. DOI: 10.3390/children11020235

79. Nayyar, A.S.; Khan, M.; Vijayalakshmi, K.R.; Suman, B.; Subhas, G.T.; Nataraju, B.; Anitha, M. Phenytoin, folic acid and gingival enlargement: Breaking myths. Contemp Clin Dent. 2014, 5(1), 59-66. DOI: 10.4103/0976-237X.128666

80. Shah, S.; Garritano, F.G. Pediatric oral anatomy. Oper. Tech. Otolaryngol. Head Neck Surg. 2015, 26(1), 2-7. DOI: 10.1016/j.otot.2015.01.007

81. Goswami, M.; Johar, S.; Khokhar, A. Oral Health Considerations and Dental Management for Epileptic Children in Pediatric Dental Care. Int J Clin Pediatr Dent. 2023, 16(1), 170-176. DOI: 10.5005/jp-journals-10005-2516

82. Gürbüz, T.; Tan, H. Oral health status in epileptic children. Pediatr. Int. 2010, 52(2), 279-283. DOI: 10.1111/j.1442-200X.2009.02965.x

83. Valmadrid, C.; Voorhees, C.; Litt, B.; Schneyer, C.R. Practice patterns of neurologists regarding bone and mineral effects of antiepileptic drug therapy. Arch. Neurol. 2001, 58(9), 1369-1374. DOI: 10.1001/archneur.58.9.1369.

84. Tripodi, D.; Cacciagrano, G.; D Ercole, S.; Verrotti, A.; Tieri, M. Effects of anti-epileptic drugs on the oral health of paediatric patients. Eur. J. Paediatr. Dent. 2023, 24(1), 45-48. DOI: 10.23804/ejpd.2023.24.01.08

85. Morgan, H.I.; Abou El Fadl, R.K.; Kabil, N.S.; Elagouza, I. Assessment of oral health status of children with epilepsy: A retrospective cohort study. Int. J. Paediatr. Dent. 2019, 29(1), 79-85. DOI: 10.1111/ipd.12432

86. Devinsky, O.; Boyce, D.; Robbins, M.; Pressler, M. Dental health in persons with disability. Epilepsy Behav. 2020, 110, Art. No: 107174. DOI: 10.1016/j.yebeh.2020.107174

87. Lauritano, D.; Moreo, G.; Limongelli, L.; Tregambi, E.; Palmieri, A.; Carinci, F. Drug-Induced Gingival Overgrowth: A Pilot Study on the Effect of Diphenylhydantoin and Gabapentin on Human Gingival Fibroblasts. Int. J. Environ. Res. Public Health 2020, 17(21), Art. No: 8229. DOI: 10.3390/ijerph17218229.

88. Rajendran, P. Lamotrigine-Induced Gingival Enlargement: An Older Problem Due to a Newer Drug - A Rare Case Report. Clin. Adv. Periodontics. 2022, 12(2), 130-133. DOI: 10.1002/cap.10123

89. Alahmari, A.M.; Alkhathaami, A.M. Gingival enlargement following levetiracetam treatment: A clinical case analysis. Epilepsia Open. 2025, 10(5), 1695-1698. DOI: 10.1002/epi4.70051

90. Ramírez-Rámiz, A.; Brunet-Llobet, L.; Lahor-Soler, E.; Miranda-Rius, J. On the Cellular and Molecular Mechanisms of Drug-Induced Gingival Overgrowth. Open Dent. J. 2017, 11, 420-435. DOI: 10.2174/1874210601711010420

91. Nandana, J.; George, J.; Priya, L.; Pidiyancheril, T.E.; Manisha, K.Y.; Menon, R.N.; Radhakrishnan, A. Are Newer Antiseizure Medications Better Off in Maintaining Oral Health in Persons with Epilepsy? Ann. Indian Acad. Neurol. 2025, 28(2), 213-219. DOI: 10.4103/aian.aian_773_24

92. Cornacchio, A.L.; Burneo, J.G.; Aragon, C.E. The effects of antiepileptic drugs on oral health. J. Can. Dent. Assoc. 2011, 77, Art. No: b140.

93. de Baat, C.; Zweer, P.G.M.A.; Vissink, A. Serie: Medicamenten en mondzorg. Proliferatie van de gingiva Medicaments and oral healthcare. Proliferation of the gingiva. Ned. Tijdschr. Tandheelkd. 2018, 125(7-8), 397-402. DOI: 10.5177/ntvt.2018.07/08.18123

Elżbieta Sołowiej

elzbieta.solowiej@wum.edu.pl

Weronika Sołowiej

Kamilla Blecharz-Klin

kamilla.blecharz-klin@wum.edu.pl

Affiliation:

a:1:{s:5:"en_US";s:131:"Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Centre for Preclinical Research and Technology ";} Poland