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

No. 2025 (Early Access)

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 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, pediatric dentistry

Similar Articles

Memet Yazar, Mustafa Sevindik, Abdullah Ozan Polat, Oğuzhan Koçer, Hilal Kuşçu Karatepe, İmran Uysal, General properties, biosynthesis, pharmacological properties, biological activities and daily uses of luteolin , Prospects in Pharmaceutical Sciences: Vol. 22 No. 4 (2024)
Kinga Kocur, Katarzyna Camlet, Anna Ziobro, Mateusz Ziomek, Wojciech Kaźmierski, Paulina Lis, Jakub Jurek, Anna Lis, Renaissance of Ketamine , Prospects in Pharmaceutical Sciences: Vol. 22 No. 3 (2024)
Katarzyna Kozon, Małgorzata Krzyżanowska, Jakub Olszewski, Andrzej Patyra, Spinal muscular atrophy – the effectiveness of treatment and new therapeutic possibilities for selected groups of patients in Poland , Prospects in Pharmaceutical Sciences: Vol. 21 No. 2 (2023)
Magdalena Bamburowicz-Klimkowska, Urszula Bogucka, Mirosław M. Szutowski, FUNCTIONS OF ATP-BINDING CASSETTE (ABC) TRANSPORTERS , Prospects in Pharmaceutical Sciences: Vol. 9 No. 3 (2011)
Paulina Dąbrowska, Michał Żuber, Michał Dacka, Efficacy and safety of bempedoic acid in lipid disorder therapy: a review of clinical trials , Prospects in Pharmaceutical Sciences: Vol. 22 No. 3 (2024)
Dr. Ashwini Madgulkar, Dr. Mangesh Bhalekar, Abhishek Kunjir, Maryam Mulla, A SCIENTIFIC EXPLORATION OF CO-AMORPHOUS FORMULATION DRIVEN BY KNOWLEDGE BASED VIRTUAL SCREENING FOR SOLUBILITY AND BIOAVAILABILITY ENHANCEMENT OF DARUNAVIR , Prospects in Pharmaceutical Sciences: No. 2025 (Early Access)
Jadwiga Turło, FUNGAL BIOTECHNOLOGY. APPLICATIONS IN PHARMACY AND SUPPLEMENTATION , Prospects in Pharmaceutical Sciences: Vol. 11 No. 3 (2013)
Katarzyna Herjan, Piotr Armański, Jakub Olszewski, Magdalena Sitnik, Maciej Bara, Positive impact of tranexamic acid in various medical settings , Prospects in Pharmaceutical Sciences: Vol. 22 No. 3 (2024)
Kinga Grużewska-Piotrowska, Agnieszka Grużewska, Medication overuse headache as a consequence of taking painkillers – a review of current literature , Prospects in Pharmaceutical Sciences: Vol. 21 No. 3 (2023)
Justyna Śledź, ORAL CAVITY CANCER - EPIDEMIOLOGICAL DATA AND RISK FACTORS , Prospects in Pharmaceutical Sciences: Vol. 13 No. 2 (2015)

<< < 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, (2025 (Early Access). 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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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):e1237-43. doi: 10.1542/peds.2006-0623 DOI: https://doi.org/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 DOI: https://doi.org/10.1177/08830738020170010201

[10] Kumar, G. Evaluation and management of drug resistant epilepsy in children. Curr. Probl. Pediatr. Adolesc. Health Care 2021, 51(7), 101035. doi:10.1016/j.cppeds.2021.101035 DOI: https://doi.org/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 DOI: https://doi.org/10.26650/jchild.2022.927535

[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), e00344. doi:10.1016/j.neurot.2024.e00344 DOI: https://doi.org/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, 1336744. doi:10.3389/fped.2024.1336744 DOI: https://doi.org/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), e87574. doi:10.7759/cureus.87574 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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, bcr2014204046 doi:10.1136/bcr-2014-204046 DOI: https://doi.org/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), 4509. doi:10.3390/ijerph19084509 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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:10.1177/08830738040190120901 DOI: https://doi.org/10.1177/08830738040190120901

[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 DOI: https://doi.org/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 DOI: https://doi.org/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. PMID: 12435021

[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. PMID: 1876981

[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, 497850. doi:10.5402/2011/497850 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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, 988601. doi: 10.3389/fped.2022.988601 DOI: https://doi.org/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, 125. doi:10.1515/pjph-2015-0035 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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, 110619. doi: 10.1016/j.yebeh.2025.110619 DOI: https://doi.org/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 DOI: https://doi.org/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), 1962. doi:10.3390/diagnostics13111962 DOI: https://doi.org/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 DOI: https://doi.org/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, 171. doi:10.12688/f1000research.22499.3 DOI: https://doi.org/10.12688/f1000research.22499.2

[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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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. PMID: 16842026

[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 DOI: https://doi.org/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), 169-74. doi: 10.1016/s1525-5050(03)00036-2. PMID: 12697142 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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, 1171. doi:10.3389/fneur.2019.01171 DOI: https://doi.org/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), e84420. doi:10.1371/journal.pone.0084420 DOI: https://doi.org/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, 1015691. doi:10.3389/fped.2022.1015691 DOI: https://doi.org/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 DOI: https://doi.org/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, b140. PMID: 22260801

[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. DOI: https://doi.org/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), 474-82. doi: 10.1902/jop.1980.51.8.474. DOI: https://doi.org/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 DOI: https://doi.org/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. PMID: 15491092

[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 DOI: https://doi.org/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 DOI: https://doi.org/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. DOI: https://doi.org/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), 1384. doi:10.3390/nu16091384 DOI: https://doi.org/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), 45. doi:10.1007/s44445-025-00053-8 DOI: https://doi.org/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), 235. doi:10.3390/children11020235 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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 DOI: https://doi.org/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), 1369-74. doi: 10.1001/archneur.58.9.1369. PMID: 11559307 DOI: https://doi.org/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 DOI: https://doi.org/10.1111/ipd.12432

[86] Devinsky, O.; Boyce, D.; Robbins, M.; Pressler, M. Dental health in persons with disability. Epilepsy Behav. 2020, 110, 107174. doi: 10.1016/j.yebeh.2020.107174 DOI: https://doi.org/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), 8229. doi: 10.3390/ijerph17218229. DOI: https://doi.org/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. DOI: https://doi.org/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. DOI: https://doi.org/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. DOI: https://doi.org/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 DOI: https://doi.org/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:b140. PMID: 22260801.

[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. DOI: https://doi.org/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