Levetiracetam Compared to Phenobarbital as a First Line Therapy for Neonatal Seizures: An Unexpected Influence of Benzodiazepines on Seizure Response.

OBJECTIVES: Neonatal seizures are common complications. Phenobarbital is the agent of choice but leads to adverse neurologic outcomes. There has been increased use of newer agents like levetiracetam. The objective of this study was determining the rate of seizure resolution in neonates treated with phenobarbital or levetiracetam. METHODS: This was a retrospective, single-center, cohort study from June 1, 2012-June 1, 2018 evaluating seizure resolution in neonates following first-line treatment with phenobarbital versus levetiracetam. Data were collected via review of the patient's charts in the electronic medical record. The primary outcome was seizure resolution without addition of a second antiepileptic agent. Logistic regression was used to assess the impact of pertinent variables. RESULTS: Each group included 73 patients. The mean gestational age was 36.01 and 37.91 weeks for the phenobarbital and levetiracetam groups, respectively (p = 0.011). The phenobarbital group had higher rates of intraventricular hemorrhage at baseline. The median birth weight was 2750 and 3002 grams in the phenobarbital and levetiracetam groups, respectively (p = 0.10). Forty-five neonates (61.6%) achieved seizure resolution with phenobarbital compared with 30 neonates (41.1%) with levetiracetam (p = 0.01). In neonates who did not receive a benzodiazepine, seizure resolution was similar between groups (51-52%). In neonates who received a benzodiazepine, seizure resolution rate was 94.1% (16/17 neonates) for phenobarbital and 18.2% (4/22 neonates) for levetiracetam. CONCLUSIONS: These findings suggest seizure resolution with levetiracetam, and phenobarbital may be impacted by benzodiazepine administration. If no benzodiazepine is used, these agents demonstrated similar efficacy. Further research into the pharmacodynamic interaction with benzodiazepines is necessary.

Effectiveness of Levetiracetam as a First-Line Anticonvulsant for Neonatal Seizures.

OBJECTIVE: Optimal treatment for neonatal seizures remains unclear, and management among US hospitals is highly varied. The purpose of this study was to evaluate the effectiveness of levetiracetam as a first-line treatment for seizures in a neonatal population. METHODS: A single-center, retrospective review of neonates at a tertiary medical center who received levetiracetam as a first-line agent after benzodiazepines for seizure control between 2015 and 2017 was conducted. Chart review was completed to analyze patient and treatment characteristics. The primary outcome was seizure control, defined as clinical seizure cessation and video electroencephalogram resolution, with no new seizures documented prior to discharge. RESULTS: A total of 36 patients met inclusion criteria. Seventeen patients (47%) had seizure control after intravenous levetiracetam as monotherapy. Eighteen patients required a second anticonvulsant, of which 13 (72%) had seizure control. In total, 30 patients (83%) had seizure control with levetiracetam monotherapy or combination therapy of levetiracetam plus fosphenytoin or phenobarbital. CONCLUSIONS: Levetiracetam monotherapy provided seizure control in about 50% of the patients reviewed. Overall, seizure control was observed in 83% of the study population that received either levetiracetam monotherapy or combination therapy of levetiracetam plus fosphenytoin or phenobarbital as a second-line agent. Further studies are warranted to directly compare historical therapies with levetiracetam for neonatal seizure control.