Comparison of Efficacy and Safety of Phenobarbital and Levetiracetam in the Treatment of Neonatal Seizures: A Systematic Review and Meta-Analysis (2000-2024)

Document Type : review article

Authors

1 Neonatal Health Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.

3 Neonatal Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/jpp.2025.90857.5594

Abstract

Background: To evaluate the efficacy and safety of phenobarbital versus levetiracetam as first-line treatments for neonatal seizures by synthesizing evidence from randomized controlled trials (RCTs) published between 2000 and 2024.
Methods: A comprehensive literature search was conducted across Medline, Embase, Web of Science, Scopus, and Cochrane Library for RCTs published from January 1, 2000, to December 31, 2024. RCTs comparing phenobarbital and levetiracetam as first-line antiseizure medications (ASMs) in neonates (0–28 days) were included. The primary outcome was seizure control, defined as seizure freedom within 24 hours of treatment initiation. Secondary outcomes included adverse effects (e.g., hypotension, respiratory depression, depressed sensorium), mortality, and neurodevelopmental outcomes. Data were extracted by two independent reviewers, and a random-effects meta-analysis was performed to account for heterogeneity, with relative risks (RR) and 95% confidence intervals (CI) calculated. The Risk of Bias version 2 tool assessed study quality.
Results: Eleven RCTs involving 821 neonates, primarily term infants with hypoxic-ischemic encephalopathy (HIE), were included. Meta-analysis showed no significant difference in seizure control between phenobarbital and levetiracetam (RR 1.11, 95% CI 0.79–1.54, I²=88%). Levetiracetam was associated with a significantly lower incidence of adverse effects, including hypotension (RR 0.28, 95% CI 0.09–0.86), respiratory depression (RR 0.36, 95% CI 0.19–0.66), and depressed sensorium (RR 0.52, 95% CI 0.27–1.00). Limited data on neurodevelopmental outcomes suggested potential benefits with levetiracetam, but evidence was inconclusive. Mortality rates were similar between groups.
Conclusion: Phenobarbital and levetiracetam demonstrate comparable efficacy in controlling neonatal seizures, but levetiracetam offers a superior safety profile with fewer adverse effects.

Keywords

References

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Journal of Pediatric Perspectives
Volume 13, Issue 11
November 2025
Pages 19789-19793

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