Phenobarbitone versus phenytoin for treatment of neonatal seizures: An open-label randomized controlled trial

Objective: To compare the efficacy of phenobarbitone and phenytoin for treatment of neonatal seizures in term and nearterm neonates. Design: Open labeled randomized controlled trial. Setting: Neonatal intensive care unit of a level II unit from India, from November 2008 to September 2009. Participants: All term and late pre-term neonates admitted with clinically apparent seizures and not having any transient metabolic disorders (hypoglycemia or hypocalcemia) were randomly assigned. Intervention: Phenobarbitone (n=54) or phenytoin (n=55) intravenously 20 mg/kg/dose over 20-30 min. Neonates whose seizures were not controlled by the assigned drug were then crossed over to be treated with other drug in same dose. Primary outcome variable: Clinical control of seizures (seizure free period of 24 hours after giving anticonvulsant). Results: Baseline characteristics including mean birthweight, gestation age and sex were comparable in both groups. Seizures were controlled in 8 of the 55 (14.5%) neonates who received phenytoin, as compared to 39 of 54 (72.2%) neonates who received phenobarbitone (P <0.001). In babies not responding to assigned drugs, after cross-over to the other drug, seizure control was achieved in 44/55 (80%) of the neonates assigned to receive phenytoin first as compared to 49/54 (91%) of those assigned to receive phenobarbitone first (P=0.014). After maximum dose of phenobarbitone seizures were controlled in 49/55(89%) in phenytoin group and 52/54 (96%) in phenobarbitone group (P<0.05). Conclusion: Phenobarbitone is more efficacious than phenytoin in control of clinical seizures in term or near-term neonates, irrespective of etiology. © 2013 Indian Academy of Pediatrics.