Levetiracetam versus Phenobarbitone in Neonatal Seizures

Seizures are the most common manifestation of neurological insult during the neonatal period. The most common cause of symptomatic neonatal seizures is hypoxic/ischemic encephalopathy (HIE) which affects approximately 1-2/100 live births.

There are no evidence-based guidelines for the pharmacologic treatment of neonatal seizures and management is highly variable.

Phenobarbitone (PB) is the mainstay for neonatal seizures treatment. While phenobarbital (PHB) has historically been used as first-line treatment for neonatal seizures, histological studies in animals have suggested that PHB (as well as phenytoin, valproic acid, vigabatrin, diazepam and midazolam) triggers widespread neuronal apoptosis in the developing brain at plasma drug levels comparable to those used for seizure control in human

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In humans, a retrospective cohort study demonstrated worse neurodevelopmental outcomes at 2 years of age following treatment of neonatal seizures with phenobarbital as compared to levetiracetam.

Levetiracetam (LEV) may have a better safety profile since it does not cause neuronal apoptosis in infant rodents. A recent review on the use of LEV in neonatal seizures revealed that complete or near complete seizure cessation was achieved in 77% of LEV, compared to 46% in PB group.

The study found that LEV was significantly more likely to result in seizure cessation at one (60%) or two (26%, total 86%) doses as compared to phenobarbital (50% first dose, 12% second dose, total 62%). Furthermore, of the subjects who continued seizing despite a second dose of PHB, 84% responded to single dose of LEV (20 mg/kg).

Regarding safety, no adverse events were seen in the current study in the LEV group, while 10 adverse events, including hypotension, bradycardia and requirement of mechanical ventilation were seen in the PHB group.

Levetiracetam achieves better control than Phenobarbitone for neonatal seizures when used as first-line antiepileptic drug, and is not associated with adverse drug reactions.

Study concludes that levetiracetam is an effective and safer alternative to phenobarbitone in the management of neonatal seizures, as a first-line AED.

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Abstract

Objective

To compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of neonatal seizures.

Design

Open labelled, Randomized controlled trial.

Setting

Level III Neonatal Intensive Care Unit (NICU).

Participants

100 neonates (0–28 days) with clinical seizures.

Intervention

If seizures persisted even after correction of hypoglycemia and hypocalcemia, participants were randomized to receive either Levetiracetam (20 mg/kg) or Phenobarbitone (20 mg/kg) intravenously. The dose of same drug was repeated if seizures persisted (20 mg/kg of Levetiracetam or 10 mg/kg of Phenobarbitone) and changeover to other drug occurred if the seizures persisted even after second dose of same drug.

Main outcome measures

Cessation of seizures with one or two doses of the first drug, and remaining seizure-free for the next 24 hours.

Results

Seizures stoped in 43 (86%) and 31 (62%) neonates in Levetiracetam and Phenobarbitone group, respectively. 10 neonates had adverse reactions in the phenobarbitone group (hypotension in 5, bradycardia in 3 and requirement of mechanical ventilation in 2 neonates) while none had any adverse reaction in Levetiracatam group.

Conclusion

Levetiracetam achieves better control than Phenobarbitone for neonatal seizures when used as first-line antiepileptic drug, and is not associated with adverse drug reactions.

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