Efficacy and Safety of Levetiracetam Versus Sodium Valproate in Pediatric Epilepsy: A Systematic Review and Meta-analysis.

OBJECTIVE

To compare the efficacy and safety of levetiracetam versus sodium valproate as antiseizure therapy in children with new-onset epilepsy or established status epilepticus.

DATA SOURCES: PubMed, Cochrane Library, Embase, and Scopus were searched from inception to March 2026, without language restriction, using combinations of "epilepsy," "status epilepticus," "pediatric," "levetiracetam," and "sodium valproate," with hand-searching of reference lists.

STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials and cohort studies of levetiracetam versus sodium valproate in children (≤18 years) were eligible. Two reviewers independently screened records, extracted data, and appraised quality (Cochrane RoB 2; Newcastle-Ottawa Scale for the cohort study). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects Mantel-Haenszel model, with certainty graded by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

DATA SYNTHESIS: Eight studies (7 randomized trials and 1 prospective cohort) were included. Levetiracetam and sodium valproate were comparably effective for seizure freedom (RR = 1.01; 95% CI = 0.93-1.10) and for failure to achieve seizure freedom (RR = 1.00; 95% CI = 0.73-1.36). Levetiracetam significantly reduced overall AEs (RR = 0.78; 95% CI = 0.68-0.89) and weight gain (RR = 0.22; 95% CI = 0.10-0.46), both high certainty. Behavioral changes (RR = 2.15; 95% CI = 0.81-5.70) and skin rash (RR = 1.01; 95% CI = 0.50-2.04) did not differ significantly.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This is among the first meta-analyses to pool pediatric data for these agents across both new-onset epilepsy and status epilepticus and to grade outcome certainty. The findings support levetiracetam as a preferred initial monotherapy when weight, tolerability, reproductive safety, or interaction risk is a priority, with behavioral monitoring during use.

CONCLUSIONS

Levetiracetam and sodium valproate offer similar seizure control in pediatric epilepsy and status epilepticus, but levetiracetam has a more favorable safety profile, particularly for adverse effects and weight gain. High-quality pediatric trials with longer follow-up are needed to confirm the long-term efficacy.