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Metabolic implications of antiepileptic therapy among children with epilepsy
Divyani Garg1, Suvasini Sharma2
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 Submission||27-Dec-2020|
|Date of Acceptance||29-Dec-2020|
|Date of Web Publication||19-Jul-2021|
Department of Pediatrics (Neurology Division), Lady Hardinge Medical College, New Delhi.
Source of Support: None, Conflict of Interest: None
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. 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.,,, 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.,,, 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., 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. 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, 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. 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, despite the enormous burden of epilepsy among Indian children. Future studies must focus on larger numbers and prospectively evaluate these concerns raised.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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