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Efficacy of Levetiracetam and Phenobarbital as First-Line Treatment for Neonatal Seizures
Carmen Verwoerd1, Jamie Limjoco1, Victoria Rajamanickam2
1Department of Pediatrics, Division of Neonatology, 5228University of Wisconsin, Madison, WI, USA.
Insights
Levetiracetam and phenobarbital showed similar efficacy in reducing neonatal seizure burden. Levetiracetam may offer a faster time to seizure freedom, warranting further study for neonatal seizure treatment.
Area of Science:
- Neonatal Neurology
- Clinical Pharmacology
- Pediatric Epilepsy
Background:
- High neonatal seizure burden is linked to adverse neurodevelopmental outcomes.
- Effective initial treatment is crucial for minimizing seizure burden in neonates.
Purpose of the Study:
- To compare the efficacy of levetiracetam versus phenobarbital as initial treatments for neonatal seizures.
- To evaluate the impact of these treatments on seizure burden and time to seizure freedom.
Main Methods:
- Retrospective cohort study of 25 neonates undergoing video electroencephalography (EEG) monitoring.
- Seizure burden was determined by analyzing video EEG data paired with medication administration times.
- Comparison of seizure burden reduction and seizure freedom rates between levetiracetam and phenobarbital groups.
Main Results:
- Similar proportions of patients achieved sustained seizure burden <10% and <20% with both levetiracetam and phenobarbital.
- Levetiracetam was associated with a shorter average time to seizure freedom (15 vs 21 hours), though not statistically significant.
- Phenobarbital showed a larger absolute reduction in average seizure burden in the hour surrounding treatment.
Conclusions:
- Initial treatment with levetiracetam and phenobarbital demonstrated comparable efficacy in reducing neonatal seizure burden.
- Levetiracetam appears promising as a first-line agent, with potential for faster seizure freedom.
- Further randomized controlled trials are needed to confirm the efficacy of high-dose levetiracetam and its long-term effects.
Abstract:
High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden <10% following initial treatment with levetiracetam, compared with 5 of 8 (63%) with phenobarbital. Thirteen (76%) patients treated with levetiracetam had sustained seizure burden <20% compared with 6 (75%) treated with phenobarbital. The phenobarbital group showed a larger absolute reduction in average seizure burden in the hour before and after treatment (-24.3 vs -14.2 minutes/h). Six of 17 (35%) patients treated with levetiracetam remained seizure free after initial treatment, compared with 2 of 8 (25%) patients treated with phenobarbital. Initial treatment with levetiracetam was associated with shorter average time to seizure freedom (15 vs 21 hours). None of these results were statistically significant. Cumulative doses of levetiracetam 100 mg/kg were well tolerated and associated with substantial decrease in seizure burden in several cases. Levetiracetam remains a promising first-line treatment for neonatal seizures; additional randomized controlled trials evaluating the effects of high-dose levetiracetam on seizure burden and long-term outcomes are warranted.
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