Comparative efficacy of first‐line antiseizure monotherapy in pediatric focal epilepsy: An umbrella review of systematic reviews and meta‐analyses
Aysu Yildiz Karaahmet, Fatma Şule Bilgiç, Adnan YükselAbstract
Introduction
First‐line antiseizure medication (ASM) monotherapy remains the recommended initial treatment for pediatric focal epilepsy. Although several ASMs are available, uncertainty persists regarding their comparative efficacy, safety, and tolerability, particularly in children. This umbrella review aimed to synthesize and map the available evidence from systematic reviews and meta‐analyses evaluating first‐line ASM monotherapies for focal epilepsy, with a focus on informing pediatric treatment decisions.
Methods
This umbrella review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidance. Systematic reviews and meta‐analyses evaluating first‐line ASM monotherapy for focal epilepsy were identified through comprehensive database searches. Data on study characteristics, patient populations, ASM comparisons, epilepsy subtypes, follow‐up duration, efficacy, safety, and tolerability outcomes were extracted and synthesized descriptively. Evidence mapping was performed to summarize the findings, and potential overlap of primary studies across the included reviews was considered. Where available, outcome‐specific certainty‐of‐evidence ratings reported by the source reviews using GRADE or CINeMA were also extracted and summarized.
Results
Sixteen systematic reviews and meta‐analyses were included, comprising randomized controlled trials and individual participant data analyses from pediatric and mixed‐age populations. Frequently evaluated ASMs included carbamazepine, lamotrigine, levetiracetam, oxcarbazepine, valproate, phenytoin, and several newer‐generation agents. Across the included reviews, no single first‐line ASM showed consistent superiority for seizure control outcomes. Selected comparisons suggested tolerability advantages for lamotrigine, levetiracetam, and some newer‐generation ASMs; however, these findings were not uniform across outcomes or reviews. Several comparative estimates were imprecise, with confidence intervals encompassing potentially clinically meaningful effects, and substantial heterogeneity was present across epilepsy subtype definitions, patient populations, follow‐up durations, and outcome reporting. The frequent inclusion of mixed‐age populations further limited the strength and direct applicability of pediatric‐specific conclusions.
Conclusions
Current umbrella‐level evidence does not establish clear superiority of one first‐line ASM over another for seizure control in pediatric focal epilepsy. Importantly, the absence of statistically significant differences should not be interpreted as evidence of therapeutic equivalence, because several estimates remain imprecise and clinically meaningful differences cannot be excluded. Interpretation is further limited by the scarcity of pediatric‐specific comparative data, the frequent inclusion of mixed‐age populations, and methodological and outcome heterogeneity across reviews. Safety and tolerability should therefore be considered alongside efficacy when individualizing treatment selection. Well‐designed pediatric‐specific comparative studies using standardized outcome measures are needed to strengthen evidence‐based treatment recommendations.