Role of levetiracetam in neonatal seizure.

Sir,

Neonatal seizures some times are very difficult to control and refractory to treatment. Neonatologists and pediatricians all over the world are using wide varieties of regimens and off-label drugs for the control of neonatal seizures. Treatment with various antiepileptic drugs like Phenobarbitone and phenytoin during neonatal period impairs physiological maturation of synapses in neurons after the initial drug insult. There are many concerns for the short-term adverse effects of phenobarbital as well as long-term effect on neurocognitive development. Levetiracetam was found not to have effect on synaptic development. Levetiracetam is considered safe because of its linear pharmacokinetics, nonhepatic elimination, lack of protein binding and no known interactions with other antiepileptic medications. Levetiracetam is approved for usage in children above 4 years of age and adults by the US Food and Drug Administration (FDA) but not for neonatal age group. Randomized controlled trials for its usage in neonatal age group are lacking. Khan O et al. studied 22 neonates on treatment with levetiracetam and showed that seizures control in majority (19) of neonates was achieved by 1 hour. All patients were seizure-free by 72 hrs. No significant side effects were reported by them.[1] Abend et al. retrospectively studied 23 neonates with seizures who received levetiracetam. They observed 50% seizure reduction within 24 hrs. Levetiracetam was associated with a greater than 50% seizure reduction in 35%, including seizure termination in 30%.[2] Shoemaker MT et al. reported three neonates with various etiologies of refractory neonatal seizures and seizures were controlled with levetiracetam. They did not report any adverse effects and these babies remained seizure-free thereafter.[3] Ramantani et al. studied 38 neonates with seizures treated with Levetiracetam and reported that it is safe and effective in controlling neonatal seizures. Various studies have reported a wide range for levetiracetam dosage ranging from 10 to 80 mg/kg/day.[1234] Merhar et al. studied the pharmacokinetics of Levetiracetam in neonates. They noted that neonates had lower plasma clearance, higher volume of distribution, and longer half-life as compared with older children and adults.[5] So the appropriate dosage of Levetiracetam in neonates needs to be studied further. Studies done on Levetiracetam were on small groups and data is insufficient for advising its routine usage in neonatal population. Further randomized controlled trials are required for using levetiracetam in neonates and for recommending an appropriate dosage for control of seizures.