Efficacy and Safety of Levetiracetam versus Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis
Eriberto R. Rayco | Paul Matthew Pasco
Discipline: medicine by specialism
Abstract:
INTRODUCTION: Seizures are the most common neurologic emergency in the neonatal
period. Phenobarbital and levetiracetam are the most commonly used anti-epileptic agents.
However, there is conflicting evidence regarding their efficacy and safety. This review aims
to synthesize data from randomized trials evaluating levetiracetam versus phenobarbital as a
first-line antiepileptic drug for seizures in the newborn.
METHODS: A systematic review and meta-analysis following the Preferred Reporting Items
for Systematic reviews and Meta-Analyses (PRISMA) guidelines was performed. The review
considered randomized clinical trials (RCTs) providing information about the efficacy and
safety of levetiracetam vs phenobarbital as first line treatment of neonatal seizures. Medline
by PubMed, CENTRAL by Cochrane, Embase, Google Scholar, and grey literature for RCTs
were searched.
RESULTS: Four randomized controlled trials met the criteria for inclusion. A total of 312
neonates (levetiracetam n=167, phenobarbital n=145) comprised the pooled sample. Seizure
freedom did not significantly favour one particular drug. This was also seen throughout
subgroup analysis comprising clinical determination of seizure onset and cessation and
neonates with hypoxic-ischemic encephalopathy. Significant heterogeniety was seen
throughout the analyses. Hypotension was seen more in patients given phenobarbital. No
significant association of either drug was seen for respiratory abnormalities and requirement
for ventilation. Mortality was not significantly associated with either drug.
CONCLUSION: This meta-analysis combined and synthesized data from four randomized
controlled trials comparing levetiracetam and phenobarbital in efficacy and safety for
neonatal seizures. The statistical analysis did not lend evidence to support the use of one drug
over the over. More studies that employ stringent techniques to minimize bias are needed for a more robust conclusion.
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