Efficacy and safety of levetiracetam versus phenobarbitone for neonatal seizures: A systemic review and meta-analysis

Abstract

Background: Neonatal seizures are a common occurrence due to a variety of etiologies such as hypoxic-ischemic encephalopathy, hypoglycemia, infections, or metabolic disorders. Levetiracetam (LEV) and Phenobarbital (PB) have been the primary choices to control seizures and their safety and efficacy have been widely investigated.

Objective: To collate studies comparing the efficacy and safety of LEV and PB and conclude on the safety profiles and adverse events of these anti-seizure medications (ASM).

Methods: We performed the analysis following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. PubMed, Cochrane Library, and Scopus databases were searched from the date of inception to October 2023. Search words "infant" or "newborn" "neonate", "seizure" or "epilepsy" or "convulsant" and "anticonvulsant" or "antiepileptic" were used, and studies that fitted our strict inclusion and exclusion were pooled to conclude on the comparative effects of LEV and PB.

Results: Of the 15 studies included in the meta-analysis, eight were Randomized Control Trials and seven were Cohorts. Of these studies, nine reported adverse effects with PB whereas only five reported adverse effects with LEV. The most commonly documented adverse effects with both ASM were hypotension and respiratory depression with only one of the studies also reporting sedation with LEV. All fifteen studies included in the meta-analysis reported the primary outcome. There was no significant difference in efficacy between LEV and PB for treating neonatal seizures (OR =1.17 95 % CI 0.76,1.79 P = 0.06).

Conclusion: Upon pooling the various studies, no significant difference was found in the efficacies of the two medications compared. However, levetiracetam had a more favorable adverse effect profile in comparison to that PB.

Keywords: Epilepsy; Hypoxic ischemic encephalopathy; Levetiracetam; Neonates; Phenobarbital; Seizures.