Single and in combination antiepileptic drug therapy in children with epilepsy: how to use it

Oliva, Claudia; Gangi, Gloria; Marıno, Silvia; Marino, Lidia; Messina, Giulia; Sciuto, Sarah; Cacciaguerra, Giuseppe; Comella, Mattia; Falsaperla, Raffaele; Pavone, Piero

doi:10.3934/medsci.2021013

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…We found that male children with low birth weight, assisted vaginal delivery, and site-specific epilepsy were less responsive to monotherapy of AEDs. A study by Oliva et al [ 13 ] also suggested that perinatal complications reduce the responsiveness of AEDs leading to the requirement of combination therapy for the same. We observed that children with low birth weight, preterm birth, and maternal history of epilepsy had lower incidences of seizure-free periods than others.…”

Section: Discussionmentioning

confidence: 99%

Kaleidoscopic Hues of Antiepileptics in Pediatric Population: Comparison of Prevailing Antiepileptics

Rout¹,

Pattanayak²,

Mishra³

et al. 2023

Cureus

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Background and objectives: Currently, we have a shortage of comprehensive information about newer antiepileptic drugs (AEDs) in the pediatric population. This might explain the discrepancies among pediatricians’ preferences in this regard. Therefore, it is crucial to study the multifaceted impacts of these drugs on children. The endpoints of our study were non-AED predictors of the requirement of combination therapy for seizure management, seizure-free period >6 months and >12 months, change in Quality of Life in Childhood Epilepsy Questionnaire - 55 (QOLCE-55), and incidence of adverse events. Methods: This prospective, observational study was conducted in KIMS, Bhubaneswar, India, from January 2021 to November 2022. Children of 2-12 years of age were treated with monotherapy of either newer antiepileptics, e.g., levetiracetam, topiramate, and oxcarbazepine or older antiepileptics, e.g., valproic acid, phenytoin, phenobarbital, and carbamazepine. Univariate and multivariate analyses were performed for the assessment of predictors. We used R software (version 4.1.1) for data analysis. Results: One hundred and ninety-eight (91.7%) of 216 enrolled participants completed this study. The mean age of the study population was 5.2 years and 117 (59%) of them were males. The univariate analysis showed that male gender, low birth weight, preterm birth, assisted vaginal delivery and site-specific epilepsy, and maternal history of epilepsy were significant predictors of combination therapy and reduced seizure-free period. There was a non-significant difference regarding the improvement of QOLCE-55 scores. None of the adverse events were serious. Conclusions: Perinatal complications and maternal history of epilepsy contribute significantly toward the efficacy of antiepileptics. However, multivariate analysis did not yield statistically significant results.

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Section: Discussionmentioning

confidence: 99%

Kaleidoscopic Hues of Antiepileptics in Pediatric Population: Comparison of Prevailing Antiepileptics

Rout¹,

Pattanayak²,

Mishra³

et al. 2023

Cureus

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“…It requires an individualized approach to the patient, exposing children to potential side effects such as decreased concentration, hyperactivity, drowsiness, as well as pain and headaches [8,9]. Epilepsy significantly diminishes the quality of life for patients and increases the risk of comorbidities such as intellectual disability or depression, and the sequential use of medications or long-term combination therapies contribute to liver damage [10,13,14]. Patients are at risk of premature death, with their life expectancy shortened by approximately 2-10 years.…”

Section: Introductionmentioning

confidence: 99%

Drug-resistant epilepsy and its selected complications in children

Knopek,

Iwanicka,

Boryczka

2024

Ann. Acad. Med. Siles.

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Padaczka lekooporna (<i>drug-resistant epilepsy</i> – DRE) u dzieci jest jedną z najczęściej diagnozowanych chorób układu nerwowego. Pomimo dostępności farmakoterapii o różnych mechanizmach działania lekooporność determinuje brak możliwości osiągnięcia zamierzonego efektu terapeutycznego. Mając na uwadze złożoną etiologię omawianej jednostki chorobowej, istnieje pilna potrzeba zgłębiania wiedzy w zakresie determinantów DRE, jak i możliwości poprawy jakości życia pacjentów oraz ich rodzin. Praca stanowi opis z podsumowaniem najnowszych osiągnięć i aktualnego stanu wiedzy odnoszącego się do charakterystyki klinicznej, epidemiologii, możliwych powikłań, a szczególnie podłoża genetycznego DRE w polskiej populacji dzieci.

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“…3 Everyday clinical practice includes therapeutic drug monitoring (TDM) as part of personalized epilepsy management regarding obvious clinical benefits, considerable morbidity, mortality, and quality of life. 4 However, it also has limitations as drug concentrations often do not correlate with improved clinical outcome. 1 Pharmacometrics approaches and mathematical simulation tools may be crucial step to improve personalized epilepsy management in vulnerable pediatric population.…”

Section: Introductionmentioning

confidence: 99%

Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population

Damnjanović,

Tsyplakova,

Stefanović

et al. 2023

Therapeutic Advances in Drug Safety

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Purpose: Unpredictable drug efficacy and safety of combined antiepileptic therapy is a major challenge during pharmacotherapy decisions in everyday clinical practice. The aim of this study was to describe the pharmacokinetics of valproic acid (VA), lamotrigine (LTG), and levetiracetam (LEV) in a pediatric population using nonlinear mixed-effect modeling, while machine learning (ML) algorithms were applied to identify any relationships among the plasma levels of the three medications and patients’ characteristics, as well as to develop a predictive model for epileptic seizures. Methods: The study included 71 pediatric patients of both genders, aged 2–18 years, on combined antiepileptic therapy. Population pharmacokinetic (PopPK) models were developed separately for VA, LTG, and LEV. Based on the estimated pharmacokinetic parameters and the patients’ characteristics, three ML approaches were applied (principal component analysis, factor analysis of mixed data, and random forest). PopPK models and ML models were developed, allowing for greater insight into the treatment of children on antiepileptic treatment. Results: Results from the PopPK model showed that the kinetics of LEV, LTG, and VA were best described by a one compartment model with first-order absorption and elimination kinetics. Reliance on random forest model is a compelling vision that shows high prediction ability for all cases. The main factor that can affect antiepileptic activity is antiepileptic drug levels, followed by body weight, while gender is irrelevant. According to our study, children’s age is positively associated with LTG levels, negatively with LEV and without the influence of VA. Conclusion: The application of PopPK and ML models may be useful to improve epilepsy management in vulnerable pediatric population during the period of growth and development.

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Single and in combination antiepileptic drug therapy in children with epilepsy: how to use it

Cited by 5 publications

References 23 publications

Kaleidoscopic Hues of Antiepileptics in Pediatric Population: Comparison of Prevailing Antiepileptics

Kaleidoscopic Hues of Antiepileptics in Pediatric Population: Comparison of Prevailing Antiepileptics

Drug-resistant epilepsy and its selected complications in children

Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population

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