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Metabolic implications of antiepileptic therapy among children with epilepsy

1 Department of Neurology, Lady Hardinge Medical College, New Delhi, India
2 Department of Pediatrics (Neurology Division), Lady Hardinge Medical College, New Delhi, India

Date of Submission27-Dec-2020
Date of Acceptance29-Dec-2020
Date of Web Publication19-Jul-2021

Correspondence Address:
Suvasini Sharma,
Department of Pediatrics (Neurology Division), Lady Hardinge Medical College, New Delhi.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_333_20


How to cite this URL:
Garg D, Sharma S. Metabolic implications of antiepileptic therapy among children with epilepsy. J Pediatr Neurosci [Epub ahead of print] [cited 2023 Dec 8]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=321796

An important consideration within the side effects profile of antiseizure medications (ASM) is the impact of these medications on metabolic parameters. Scientific literature is replete with descriptions of the adverse metabolic profile of the older or first and second generation ASMs, such as carbamazepine, valproate, phenytoin, phenobarbitone, and to a lesser extent, among the newer ASMs.[1] ASMs, particularly enzyme-inducing drugs, can precipitate early atherosclerosis. However, in resource-limited settings such as India, these older medications continue to maintain a stronghold in the epilepsy therapeutic armamentarium due to their affordability and wide availability. Hence, epilepsy practitioners in our settings must be aware of these metabolic effects.

A number of cross-sectional as well as prospective studies demonstrate an association between duration of ASM usage and the development of vascular metabolic risk factors.[1],[2],[3],[4] These adverse effects are broad and range from hyperhomocysteinemia, derangement of lipid profile, elevated uric acid level, development of weight gain and obesity, thyroid dysfunction, insulin resistance, and diabetes.[1],[2],[3],[4] Increasingly, carotid intima-media thickness (CIMT) has been reported as a marker of early atherosclerosis among children with epilepsy who were on valproate, or even levetiracetam, lamotrigine or topiramate.[5],[6] Whether these findings can be delinked with adverse effects of these ASMs on lipid levels is unclear.

In the present cross-sectional study from southern India, adverse metabolic effects of ASMs on CWE have been compared to healthy children.[7] This study bulks the limited data from India on this issue. Interestingly, the authors of this study observed worse metabolic effects of oxcarbazepine compared to even valproate and also levetiracetam. This finding, which has been echoed in previous studies as well,[8] has concerning connotations as both carbamazepine and oxcarbazepine remain preferred drugs for focal epilepsy. Additionally, children on polytherapy (≥ASMs) had significantly more insulin resistance compared to children on monotherapy or controls.

The study raises a few questions which are pertinent to ask in this respect. Should there be regular screening of metabolic parameters among CWE, particularly if they are being managed with the older ASMs? At what point into the treatment course should this be initiated, and what should be the frequency of screening? This would be of particular relevance among CWE who will remain on ASMs for definitely prolonged periods, such as those with Juvenile Myoclonic Epilepsy (JME) who embark on antiepileptic treatment at relatively younger age. It is known that long-term therapy with ASMs contributes to acceleration of atherosclerosis.[9] Moreover, children with drug-resistant epilepsy who are on polytherapy may require more stringent monitoring.

Data among CWE in India is fairly limited regarding metabolic considerations of antiseizure medications,[10] despite the enormous burden of epilepsy among Indian children. Future studies must focus on larger numbers and prospectively evaluate these concerns raised.

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Conflicts of interest

There are no conflicts of interest.

   References Top

El-Farahaty RM, El-Mitwalli A, Azzam H, Wasel Y, Elrakhawy MM, Hasaneen BM. Atherosclerotic effects of long-term old and new antiepileptic drugs monotherapy: a cross-sectional comparative study. J Child Neurol 2015;30:451-7.  Back to cited text no. 1
Hamed SA. Atherosclerosis in epilepsy: its causes and implications. Epilepsy Behav 2014;41:290-6.  Back to cited text no. 2
Eirís J, Novo-Rodríguez MI, Del Río M, Meseguer P, Del Río MC, Castro-Gago M. The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy. Epilepsy Res 2000;41:1-7.  Back to cited text no. 3
Verrotti A, Basciani F, Morresi S, Morgese G, Chiarelli F. Thyroid hormones in epileptic children receiving carbamazepine and valproic acid. Pediatr Neurol 2001;25:43-6.  Back to cited text no. 4
Karatoprak E, Tosun O. Effects of valproic acid and levetiracetam monotherapy on carotid intima-media and epicardial adipose tissue thickness in non-obese children with epilepsy. Brain Dev 2020;42:165-70.  Back to cited text no. 5
Mehrpour M, Shojaie M, Zamani B, Gharibzadeh S, Abbasi M. Atherogenic consequence of antiepileptic drugs: a study of intima-media thickness. Neurol Sci 2014;35:253-7.  Back to cited text no. 6
XXXX. Metabolic effects of long-term antiepileptic drug therapy in south Indian children- a case control study. J Pediatr Neurosc2021;XX:XX-XX.  Back to cited text no. 7
Garoufi A, Koemtzidou E, Katsarou E, Dinopoulos A, Kalimeraki I, Fotinou A, et al. Lipid profile and thyroid hormone concentrations in children with epilepsy treated with oxcarbazepine monotherapy: a prospective long-term study. Eur J Neurol 2014;21:118-23.  Back to cited text no. 8
Tan TY, Lu CH, Chuang HY, Lin TK, Liou CW, Chang WN, et al. Long-term antiepileptic drug therapy contributes to the acceleration of atherosclerosis. Epilepsia 2009;50:1579-86.  Back to cited text no. 9
Dhir A, Sharma S, Jain P, Bhakhri BK, Aneja S. Parameters of metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. J Pediatr Neurosci 2015;10:222-6.  Back to cited text no. 10
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