Randomized Controlled Trial Evaluating Levetiracetam as First-line Therapy for Seizures in Neonates

This multicenter, randomized, blinded, controlled, trial investigated the efficacy and safety of levetiracetam compared with phenobarbital as a preferred treatment for neonatal seizures of any cause. The primary outcome variable was complete seizure freedom for 24 hours, assessed by independent review of the EEGs by 2 experts. Eighty percent of patients randomly assigned to phenobarbital remained seizure free for 24 hours, compared with 28% of patients randomly assigned to levetiracetam (P, .001; relative risk 0.35 [95% confidence interval: 0.22–0.56]; modified intention-to-treat population). A 7.5% improvement in efficacy was achieved with a dose escalation of levetiracetam from 40 to 60 mg/kg. More adverse effects were seen in subjects randomly assigned to phenobarbital (not statistically significant). The authors concluded that phenobarbital was more effective than levetiracetam for the treatment of neonatal seizures and higher rates of adverse effects were seen with phenobarbital treatment.