Objective: To study the effect of commonly prescribed anti epileptic drugs as Carbamazepine, Phenytoin and  newer antiepileptic drug as Lamotrigine, Levetiracetam on lipid profile of epileptic children (2-12 yrs) who had taken them for long term presented in outdoor or indoor  Department of Pediatrics, Darbhanga Medical College and Hospital, Laheriasarai.

Method: Prospective observational study done in indoor and outdoor of Department of Pediatrics, Darbhanga Medical College and Hospital, Laheriasarai. All children aged 2 years to 12 years, of either sex having partial or generalized seizures and recently started on anti-epileptic drugs, (Carbamazepine, Phenytoin, Lamotrigine, Levetiracetam) were selected for 6 months from March 2012 to august 2012. Patients who had taken prior anticonvulsant  or taking more than one AED, family history of dyslipidemia, metabolic disease or disease which has propensity to alter lipid profile like diabetes mellitus, nephrotic syndrome, hypothyroidism, storage diseases, renal failure and cholestatis were  excluded from the study. Patients were classified into 4 groups: (1) PHT-treated subgroup (22 patients); (2) CBZ-treated group (23 patients); (3) Lamotrigine - treated group (6patients) (4). Levetiracetam treated group (10 patients) in all cases patients were adequately treated. Serum lipid profile included total cholesterol (TC), triglycerides (TG), LDL-Cholesterol (low density lipoprotein cholesterol) and HDL-Cholesterol (high density lipoprotein cholesterol). These were done before and after treatment with AED over 6 and 12 months The study was approved by ethical committee of DMCH.  All investigations were done in department of pathology, DMCH.

Results: Cases were selected for 6 months from March 2012 to august 2012 and followed up for 12 months, total 18 months .79 cases were selected and followed up. 18 patients were lost to follow-up and 61 cases were followed up till 12 months. So we ended up with 61 patients in which 31.1% (n=19) were females and 68.8 %( n=42) were males.77.0 %(n=47) patients were above 6 yr of age.  73.7% patients were taking older enzyme inducing AED (CBZ & PHT, n=45) while 26.2% (n=16) of patients taking Levetiracetam & Lamotrigine. Carbamazepine (CBZ) significantly increases the total cholesterol, HDL cholesterol, Triglycerides, LDL cholesterol. Increase in the Total Cholesterol: HDL and LDL: HDL ratio is not significant. There was significant increase in mean Total Cholesterol, Triglycerides, HDL, LDL in patients treated with Phenytoin (PHT). There was no significant increase in ratio of LDL/HDL and Total cholesterol / HDL. Lamotrigine produces no significant increase in the Total Cholesterol, HDL, LDL, Triglycerides or any other alterations in the ratio of Total Cholesterol: HDL and LDL: HDL  Levetiracetam  showed a significant increase in Total cholesterol , Triglycerides , HDL, But there was no statistical significance of its effect on LDL cholesterol or the ratios of Total Cholesterol: HDL and LDL: HDL ratio.

Conclusion: Hepatic enzyme inducers like Carbamazepine, Phenytoin and new AED Levetiracetam may have adverse effect on serum   lipid profile. These alterations in serum lipids may have clinical relevance in development of atherosclerosis thus causing cardiovascular disease (CVD). Lamotrigine has no significant effect on lipid profile thus may be preferred over enzyme inducing AED when effect on serum lipid profile is considered. Monitoring of serum lipid should be done in children with epilepsy taking Carbamazepine Phenytoin and levetiracetam.

Keywords: older antiepileptic drugs, Newer antiepileptic drugs, serum lipid profile, hepatic enzyme inducers, cardiovascular disease.

1. WHO Epilepsy in the WHO region: Bridging the Gap: The Global Campaign Against Epilepsy.:”Out Of the Shadows”. Geneva: WHO;2004
2. Ngugi AK, Bottomley C, Kleinschimdt I, Sander J W ,Newton C R. Estimation of the burden of active and life time epilepsy: a meta-analytiacal approach.Epilepsia 2010;51:883-890  Pubmed
3. Mac TL, Tran DS, Quet F, Odermatt P. Epidemiology, aetiology, and clinical management of epilepsy in Asia: a systematic review. Lancet Neurol. 2007; 6:533–43.
4. Luoma, P.V., Pelkonen, R.O., Myllyla, V., Sotaneimi, E.A. (1989) Relationship between serum lipid levels and indices of drug metabolism in epileptic on anticonvulsant. Clinical.Pharmaocol.Therp.25, 235-237.
5. Smith, D.B., Delgade, E.S., Cueta, A.V., Cramer, J.A., Maltson, R.H. (1983) Historical prospective on the choice of antiepileptic drug for the treatment of seizures in adults. Neurology. 33, 2-4.
6. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1257-66.
7. Fisher RS, Boas WVE, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: Definitions proposed by the Interna-tional League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-2.
8. Sridharan R, Murthy BN. Prevalence and pattern of epilepsy in India. Epilepsia 1999; 40:631-6.
9. Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990;I:228-37.
10. Billings RE. Interactions between folate metabolism, phenytoin metabolism, and liver microsomal cytochrome P450. Drug Nutr Interact 1984;3:21-32.
11. Tümer L, Serdaroglu A, Hasanoglu A, Biberoglu G, Aksoy E: Plasma homocysteine and lipoprotein (a) levels as risk factors for atherosclerotic vascular disease in epileptic children taking anticonvulsants. Acta Paediatr, 2002, 91, 923–926.
12. Annegers JF, Hauser WA, Shirts SB: Heart disease mortality and morbidity in patients with epilepsy. Epilepsia, 1984, 25, 699–704.
13. Elliott JO, Jacobson MP, Haneef Z: Cardiovascular risk factors and homocysteine in epilepsy. Epilepsy Res, 2007, 76, 113–123.
14. Gaitatzis A, Carroll K, Majeed A, WSander J: The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia, 2004, 45, 1613–1622.
15. Muuronen A, Kaste M, Nikkilä EA, Tolppanen EM: Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study. Br Med J, 1985, 23, 1481–1483.
16. Glass CK, Witztum JL: Atherosclerosis: the road ahead. Cell, 2001, 104, 503–516.
17. Demircioðlu S, Soylu A, Dirik E: Carbamazepine and valproic acid: effects on the serum lipids and liver functions in children. Pediatr Neurol, 2000, 23, 142–146.
18. Hamed S, Hamed E, Hamdy R, Nabeshima T: Vascular risk factors and oxidative stress as independent predictors of asymptomatic atherosclerosis in adult patients with epilepsy. Epilepsy Res, 2007, 74, 183–192.
19. Rho JM and Sankar R: The pharmacologic basis of antiepileptic drug action. Epilepsia 1999; 40(11):1471-1483.
20. Sirven JI, Noe K, Hoerth M and Drazkowski J: Antiepileptic drugs: recent advances and trends. Mayo Clinic Proceedings 2012; 87(9):879-889.
21. Luoma PV, Myllyla¨ VV, Sotaniemi EA, Lehtinen IA, and Hokkanen EJ.Plasma high density lipoprotein cholesterol in epileptics treated with various anticonvulsants .EurNeurol19:67–72, 1980.
22. Brown DW, Ketter TA, Crumlish J, Post RMCarbamazepine-induced increases in total Serum cholesterol: clinical and theoretical implications.. J Clin Psychopharmacol12: 431–437,1992
23. Nermin Bolukbasi, FerdaAkar, SinanBir the effects of Antiepileptic Drugs on Lipid Profiles and Liver Enzymes (Archives of Neuropsychiatry 2011; 48: 11-6).
24. Manimekalai, B. Visakan etal Journal of Clinical and Diagnostic Research. 2014 Aug, Vol-8(8): HC05-HC09
25. Yis U, Dog an M. Effects of oxcarbazepine treatment on serum lipids and carotid intima media thickness in children. Brain Dev. 2012;34(3):185-88.
26. Nikkila, M. Kaste, C.Ehnholm, J.ViikariIfrom the Third Department of Medicine, University of Helsinki, Finland Increase of serum high-density lipoprotein in phenytoin users. Acta Medica Scandinavica Volume 204, Issue 1-6,517–520, January/December 1978.
27. Calandre EP, Porta BS, Dolores Calzada GDL. The Effect of Chronic phenytoin Treatment on Serum Lipid Profile in Adult Epileptic Patients. Epilepsia. 1992:33 (1):154-57.
28. Dewan P, Aggarwal A, Faridi A. Effect of phenytoin and valproic acid therapy on serum lipid levels and liver function tests. Indian Pediatrics. 2008;45:855-58.
29. Castro-Gago M, Novo-Rodríguez MI, Blanco-Barca MO, Urisarri-Ruíz de Cortázar A, Rodríguez-García J, Rodríguez-Segade S, Eirís-Puñal J: Evolution of serum lipids and lipoprotein (a) levels in epileptic children treated with carbamazepine, valproic acid, and phenobarbital. J Child Neurol, 2006, 21, 48–53.
30. Demircioðlu S, Soylu A, Dirik E: Carbamazepine and valproic acid: effects on the serum lipids and liver functions in children. Pediatr Neurol, 2000, 23, 142–146.
31. Franzoni E, Govoni M, D’Addato S, Gualandi S, Sangiorgi Z, Descovich GC, Salvioli GP: Total cholesterol, high-density lipoprotein cholesterol, and triglycerides inchildren receiving antiepileptic drugs. Epilepsia, 1992, 33, 932–935.
32. Gibbons GF. The role of cytochrome P450 in the regulation of cholesterol biosynthesis. 2002;37:1163-70.
33. Svalheim, G, Luef, M. Rauchenzauner, L. Mørkrid, L. Gjerstad, E. Taubøll The Cardiovascular risk factors in epilepsy patients taking levetiracetam, carbamazepine or lamotrigine. (Acta Neurologica Scandinavica, 122: 30–33. doi: 10.1111/j.1600- 0404.2010.01372.x)
34. Chuang YC, Chuang HY, Lin TK, Chang CC, Lu CH, Chang WN, Chen SD, Tan TY, Huang CR, Chan SHThe Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Epilepsia. 2012 Jan; 53(1):120-8.

Madhurima Prasad M.B.B.S, MS (Surgery)

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