Anti-Epileptic Drug Toxicity in Children

Abstract

Anti-epileptic drugs (AEDs) have had a major impact on children, improving their quality of life and significantly reducing both morbidity and mortality. They are, however, associated with significant toxicity. Behavioural problems and somnolence are the most frequent adverse drug reactions for many AEDs. Unfortunately, the comparative risk of drug toxicity for different AEDs has been inadequately studied. Drug toxicity is poorly reported in randomised controlled trials. Prospective cohort studies are the best way to study drug toxicity. There have been a few prospective cohort studies of children with epilepsy, but the numbers of children have been small. Systemic reviews of the toxicity of individual AEDs have been helpful in identifying the risk of drug toxicity. Parents of children with epilepsy and the children and young people who are due to receive AED treatment have the right to know the likelihood of them experiencing drug toxicity. Unfortunately, the evidence base on which health professionals can provide such information is limited.

Correlation of elevated lamotrigine and levetiracetam serum/plasma levels with toxicity: A long-term retrospective review at an academic medical center

“…Our findings with levetiracetam also largely match the reported literature [ 17 , [22] , [23] , [24] , [25] , [26] , [27] , [28] ]. In our study, approximately 45 % of patients with a levetiracetam serum/plasma level of 80 mg/L or higher were asymptomatic.…”

“…Dose adjustments are required for those with renal insufficiency [ 3 , 4 ]. Overdoses are typically well tolerated, with the majority of patients remaining asymptomatic [ 17 , [22] , [23] , [24] , [25] , [26] , [27] , [28] ]. The proposed reference range is 12–46 mg/L [ 19 ].…”

Analysis of Adverse Drug Reactions in Pediatric Patients with Epilepsy: An Intensive Pharmacovigilance Study

“…The annual cost of adverse events in hospital care amounts to hundreds of billions of US dollars worldwide [20]. Prospective studies have suggested that between one-third and up to two-thirds of children who receive ASM will experience an ADR and that the risk of an ADR is significantly higher among patients receiving polytherapy than among those receiving monotherapy [15,21,22]. Additionally, ASM-ADRs have been associated with fatality, elevated frequency, and high severity [15,23,24]; however, clinical information regarding their frequency, efficacy, and safety is often not registered and, therefore, not reported.…”

Alterations of Plasma Pro-Inflammatory Cytokine Levels in Children with Refractory Epilepsies

“…Nonetheless, the research on the role of inflammation in the pathogenesis of Developmental and Epileptic Encephalopathies is of particular clinical importance. The currently available anti-seizure medications are neither preventive nor curative and have multisystem side-effects, including reduced cognitive and memory function, as well as behavioural problems in children [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Additionally, the abovementioned proinflammatory markers are one of the plentiful groups that are keenly overexpressed in epileptic zones, implying that via targeted anti-inflammatory immunotherapies these may be novel therapeutic keys in the future in amending mechanisms of epileptogenesis to prevent seizure recurrence and refractoriness in epilepsies [ 31 ].…”