Effect of Antiepileptic Drugs on Serum Lipid Profile among Children with Epilepsy at a Tertiary Care Hospital, Chennai, India

Abstract

Introduction: An arsenal of Antiepileptic Drugs (AED) is used in the management of childhood seizure disorders. Most of them are taken long-term. These drugs have the potential to cause hyperlipidemia by inducing the P450 enzyme system. The alteration in lipid profile caused by long-term use of antiepileptic drugs in children needs to be studied to reduce the risk of future atherosclerosis. Aim: To analyse the effect of antiepileptic drugs on serum lipid profile in children with epilepsy in a tertiary care. Materials and Methods: This prospective descriptive study was conducted in the Outpatient and Inpatient Wards of the Department of Paediatrics and Neurology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India, from February 2017 to September 2017. The study involved a total of 155 children, who were on monotherapy antiepileptic drugs for atleast 6 months (33 on phenytoin, 42 on phenobarbitone, 20 on levetiracetam, 20 on carbamazepine, 40 on sodium valproate). A corresponding numbers of children, who attended the General Outpatient Department for acute upper respiratory tract and were otherwise healthy, were included as controls. A blood sample (3 mL) was drawn after an overnight fast for serum glucose, liver enzymes, total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), Low Density LipoproteinCholesterol (LDL-C), Very Low Density Lipoprotein (VLDL) cholesterol and Triglycerides (TG) measurement. Chi-square test was performed to find out the significance of association and independent t-test was used to compare the mean between various groups. Results: Cytochrome P450 (CYP) enzyme inducers like carbamazepine, phenytoin and phenobarbitone significantly modified serum lipids in epileptic children when compared to healthy controls. In children on long-term phenytoin monotherapy, mean cholesterol levels were significantly higher in the cases compared to controls (156.73±31.93 mg/dL vs 105.03±8.60 mg/dL, p-value <0.0001), significantly elevated triglycerides (123.48±25.99 mg/dL vs 87.88±12.16 mg/dL, p-value <0.0001), and HDL-C level was significantly lower (44.52±10.14 mg/ dL vs 56.73±12.56 mg/dL, p-value <0.0001) than in controls. Phenobarbitone use was associated with significantly higher levels of cholesterol (164.97±34.41 mg/dL vs 107.76±9.28 mg/dL, p-value <0.0001), LDL (155.27±28.55 mg/dL vs 93.36±6.81 mg/ dL, p-value <0.0001), and triglycerides (125.55±42.19 mg/dL vs 86.30±8.12 mg/dL, p-value <0.001) and lower HDL (46.30±9.47 mg/dL vs 57.73±14.41 mg/dL, p-value <0.0001). Levetiracetam was not associated in significant alteration in both liver enzymes and lipid profile (p-value >0.05). Carbamazepine monotherapy was associated with higher levels of cholesterol (180.50±28.06 mg/dL vs 112.15±13.55 mg/dL, p-value <0.0001), LDL (138.85±22.55 mg/dL vs 82.45±12.12 mg/dL, p-value<0.0001) and triglycerides (142.80±9.48 mg/dL vs 85.40±6.29 mg/dL, p-value <0.0001) when compared to healthy controls. There was no alteration in lipid profile in valproate monotherapy. Valproate monotherapy was associated with significant increase in levels of SGOT and SGPT when compared to mean levels (40.35±11.208 (IU/L), and 40.70±8.809 (IU/L), respectively) observed in other AEDs and significant increase in SGPT levels when compared to healthy controls (36.50±10.61(IU/L) in cases vs 40.70±8.81 (IU/L) in controls). Conclusion: Levetiracetam did not produce significant changes in the serum lipid profile and liver enzymes and appears to be safe to use in children for long-term epilepsy management especially in children with baseline deranged lipid profile.