The impact of antiepileptic drug therapy on oral health in children with epilepsy: current evidence, mechanisms, and management strategies
DOI:
https://doi.org/10.56782/pps.809Keywords:
AEDs, antiepileptic drugs, anticonvulsants adverse effects, oral health, gingival overgrowthAbstract
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.
Downloads
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
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Elżbieta Sołowiej, Weronika Sołowiej, Kamilla Blecharz-Klin

This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.