Levetiracetam versus carbamazepine monotherapy in the management of pediatric focal epilepsy: A systematic review and meta-analysis of randomized controlled trials

Abstract

Levetiracetam (LEV) and carbamazepine (CBZ) are effective monotherapies for focal epilepsy in children. However, the best drug remains controversial. Therefore, we performed a systematic review and meta-analysis comparing LEV and CBZ monotherapy in the management of pediatric focal epilepsy (PFE). We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) published until February 2024 comparing LEV and CBZ monotherapy in PFE. Statistical analysis was performed using R version 4.2.2, heterogeneity was assessed using I² statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered significant. The outcomes of interest were seizure freedom, any adverse events, adverse events leading to treatment discontinuation, dermatologic adverse events, and the frequency of at least one seizure, defined as the proportion of patients experiencing one or more seizures during the treatment period. Four RCTs comprising 381 children with a mean age of 7.32 to 9.28 years were included, of whom 186 (48.8%) received LEV monotherapy. There was no significant difference between groups (RR: 1.15; 95% CI 0.88-1.50; p = 0.31; I² = 90%) regarding seizure freedom. The frequency of at least one seizure (RR: 0.71; 95% CI 0.52-0.97; p = 0.03; I² = 8%) and dermatologic adverse events (RR: 0.24; 95% CI 0.09-0.64; p < 0.01; I² = 0%) were both significantly lower in the LEV group. There were no significant differences in the presence of any adverse events (RR: 0.58; 95% CI 0.33-1.01; p = 0.05; I² = 36%) or adverse events leading to treatment discontinuation (RR: 0.67; 95% CI 0.13-3.42; p = 0.63; I² = 30%).Conclusion: In monotherapy, LEV was more advantageous than CBZ for PFE, with a lower frequency of seizures and fewer dermatological adverse events. However, both drugs are equally effective in achieving seizure freedom, adverse events without specification, and those that lead to treatment discontinuation. Our findings have important implications for clinical practice and decision-making in this condition.

Keywords: Carbamazepine; Focal epilepsy; Levetiracetam; Monotherapy; Pediatric.

Fig. 1

PRISMA flow diagram of study screening and selection

Fig. 2

There was no significant difference in seizure freedom between patients undergoing monotherapy with LEV and those with CBZ

Fig. 3

There were significant differences between patients undergoing monotherapy with LEV compared to CBZ for the following outcomes: a frequency of at least one seizure; b dermatologic adverse events

Fig. 4

There were no significant differences between patients undergoing monotherapy with LEV or CBZ for the following outcomes: a any adverse events; b adverse events leading to treatment discontinuation

Fig. 5

The sensitivity analyses confirmed the robustness of the results, with slightly adjusted but still non-significant effect estimates for the following outcomes: a seizure freedom; b any adverse events; and c adverse events leading to treatment discontinuation

Fig. 6

Risk of bias assessment

Fig. 7

Funnel plots for each outcome showed symmetrical distributions around the pooled effect size, indicating low publication bias and consistent findings across studies, except for seizure freedom and dermatologic side effects; with more studies on one side than on the other