# Efficacy of Levetiracetam Use in Neonatal Seizure: A Retrospective Cohort Study

## TL;DR

Levetiracetam is a safe and effective alternative to phenobarbital for managing neonatal seizures, with fewer side effects and high seizure control rates.

## Contribution

The study provides evidence that levetiracetam has a superior safety profile and high efficacy in neonatal seizure management compared to phenobarbital.

## Key findings

- Levetiracetam achieved seizure control in 83% of cases as monotherapy or adjunct therapy.
- Phenobarbital was associated with more side effects (57%) compared to levetiracetam (10%).
- Higher levetiracetam doses (up to 60 mg/kg) may be needed in complex cases like HIE.

## Abstract

Safety Profile: LEV avoids the risk of neuronal apoptosis and hippocampal transcriptome dysregulation associated with traditional GABAergic agents like phenobarbital.Clinical Efficacy: Successful seizure control was achieved in up to 83% of cases when LEV was used either as monotherapy or combined with standard care.Electroclinical Dissociation: A critical risk when combining LEV and PB; visible movements may stop while electrical brain activity continues, necessitating the use of cEEG or aEEG for accurate burden assessment.Dosing Optimization: Emerging data suggests higher loading doses (up to 60 mg/kg) may be required in complex cases like HIE to reach therapeutic targets.Future Directions: Transitioning LEV from a refractory-use medication to a primary agent requires large-scale RCTs focusing on long-term neurodevelopmental outcomes.

Safety Profile: LEV avoids the risk of neuronal apoptosis and hippocampal transcriptome dysregulation associated with traditional GABAergic agents like phenobarbital.

Clinical Efficacy: Successful seizure control was achieved in up to 83% of cases when LEV was used either as monotherapy or combined with standard care.

Electroclinical Dissociation: A critical risk when combining LEV and PB; visible movements may stop while electrical brain activity continues, necessitating the use of cEEG or aEEG for accurate burden assessment.

Dosing Optimization: Emerging data suggests higher loading doses (up to 60 mg/kg) may be required in complex cases like HIE to reach therapeutic targets.

Future Directions: Transitioning LEV from a refractory-use medication to a primary agent requires large-scale RCTs focusing on long-term neurodevelopmental outcomes.

Neonatal seizures are common complications in neonatal intensive care units. They have been noticed to be more common in preterm infants, but they can also affect term infants. Levetiracetam is a broad-spectrum antiepileptic drug that has been studied to manage seizures, yet limited data are available on its use in neonatal seizures. Objectives: Study the effect of levetiracetam on neonatal seizures in terms of maintaining seizure freedom after the initiation of levetiracetam and investigating its safety profile in the neonate population. Method: Retrospective cohort study comparing two groups of patients identified through accessing their medical profiles after searching the following keywords: phenobarbital, levetiracetam, and neonatal seizures amongst all NICU admissions in King Abdulaziz Medical City, Ministry of National Guard Health Affairs, from the period between December 2016 and January 2020. Forty-eight patients were included based on the inclusion/exclusion criteria. The selected sample was further subclassified into 28 neonates who received phenobarbital and 20 who received levetiracetam. Results: Seizure control was significantly observed in neonates with onset <24 h and those born at <37 weeks GA. In the first arm, 22 out of 28 neonates achieved seizure freedom while using phenobarbital; in the second arm, 11 out of 20 neonates achieved seizure control on levetiracetam after failing with phenobarbital. While seizure control was better achieved by phenobarbital, it was found that almost 57% of the first arm developed side effects on phenobarbital; however, only 10% of the neonates on levetiracetam developed side effects. While PB remains effective for acute suppression, LEV demonstrated a superior safety profile with no serious adverse events and a high rate of successful seizure management as an add-on therapy (83% control in combined cohorts). Conclusions: The study concluded that using levetiracetam could result in improved outcomes. LEV is a safe and effective alternative or adjunct to PB. Its use may mitigate the neurotoxic risks associated with GABAergic drugs, though continuous EEG monitoring is essential to ensure electrical seizure cessation and avoid electroclinical dissociation. The number of patients who received levetiracetam initially is not considered a representative sample to reach a conclusion on the use of levetiracetam as an effective monotherapy.