Levetiracetam Versus Phenobarbital for Neonatal Seizures: A Randomized Controlled Trial

Area of Science:

• Neonatal neurology
• Pediatric epilepsy
• Clinical pharmacology

Background:

• No US Food and Drug Administration-approved therapies exist for neonatal seizures.
• Phenobarbital and phenytoin are common treatments but often fail and raise safety concerns for the developing brain.
• Levetiracetam shows promise due to its efficacy and safety profile in older patients.

Purpose of the Study:

• To compare the efficacy and safety of levetiracetam versus phenobarbital as a first-line treatment for neonatal seizures.
• To evaluate levetiracetam's potential as an alternative first-line therapy for neonatal seizures.

Main Methods:

• A multicenter, randomized, blinded, controlled, phase IIb trial.
• Investigated levetiracetam compared with phenobarbital for neonatal seizures of any cause.
• Primary outcome: complete seizure freedom for 24 hours, assessed by independent EEG review.

Main Results:

• Phenobarbital achieved 24-hour seizure freedom in 80% of patients, versus 28% for levetiracetam (P < .001).
• A levetiracetam dose escalation from 40 to 60 mg/kg improved efficacy by 7.5%.
• More adverse effects were observed in the phenobarbital group, though not statistically significant.

Conclusions:

• Phenobarbital demonstrated superior efficacy compared to levetiracetam in this phase IIb study for neonatal seizures.
• Phenobarbital treatment was associated with higher rates of adverse effects.
• Further research with higher doses of levetiracetam and long-term outcome measures is needed.