Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

Kaushik Ragunathan, Jayakumar Chandrasekhar


Background: Neonatal seizure management has not changed much in the last 50 years. Neuronal apoptosis in animal models and cognitive impairment in human subjects has been reported with the use of Phenobarbitone. Levetiracetam is advantageous as it is effective, well tolerated and has least drug interactions.

Methods: This double blinded, randomized, parallel group, active controlled study was conducted among 66 neonates in the Neonatal intensive care unit of a tertiary care hospital for a period of 18 months. Neonates with seizures fulfilling the inclusion criteria were treated either with Phenobarbitone or Levetiracetam. Seizure control was defined as no seizure activity within 40 minutes of the administration of the first drug. Failure of first line agent was treated with Phenytoin. Neonates were observed for a period of 14 weeks for recurrence of seizure and any serious adverse effects.

Results: Effective seizure control was achieved in 64.7% neonates in Levetiracetam group as compared to 31.2% in Phenobarbitone group (p <0.05). Early resumption of breast feeds within 6 hours of therapy was achieved in 73.5% neonates treated with Levetiracetam compared to 31.2% neonates treated with Phenobarbitone (p value = 0.001).

Conclusions: Levetiracetam is a promising alternative as first line Anti-epileptic drug in neonates with seizures. Prolonged sedation was the adverse effect noted to Phenobarbitone that made breast feeding and neuro- assessment difficult. No serious adverse effects were seen with Levetiracetam.


Antiepileptic drug, Levetiracetam, Phenobarbitone, Neonate, Efficacy, Newborn seizures, Randomized controlled study

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Martin J, Fanaroff A, Walsh C. Fanaroff and Martin's Neonatal-Perinatal Medicine. 8th ed. Philadelphia : Mosby, An Imprint of Elsevier; 2006.

Mohamad A. Mikati. Neonatal seizures. In: Kliegman, Stanton, Geme III, Schor, Behrman. Nelson Textbook of Pediatrics. 19th Edition. Vol 2 2011;:2033.

Booth D, Evans DJ. Anticonvulsants for neonates with seizures. In: Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2004. Available at: http:// onlinelibrary. Accessed 18 September 2015.

Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15(1):1-7.

Painter MJ, Scher MS, Stein AD, Armatti S, Wang Z, Gardiner JC, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341(7):485-489.

Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011;44(4):265-269.

Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol. 2013;33(11):841-6.

Volpe J. Neonatal Seizures. N Engl J Med. 1973;289:413-6.

Castro CJR, Borges HAA, Martinez DE, Campo GC, Soler PR. Midazolam in neonatal seizures with no response to phenobarbital. Neurology. 2005;64(5):876-9.

Silverstein FS, Ferriero DM. Off label use of antiepileptic drugs for the treatment of neonatal seizures. Pediatr Neurol. 2008;39(2):77-9.

Furwentsches A, Bussmann C, Ramantani G, Ebinger F, Philippi H, Pöschl J, et al. Levetiracetam in the treatment of neonatal seizures: A pilot study. Seizure. Euro J Epilepsy. 2010;19(3):185-9.

Shoemaker MT, Rotenberg JS. Levetiracetam for the treatment of neonatal seizures. J Child Neurol. 2007;22(1):95-8.

Rakshasbhuvankar A, Rao S, Kohan R, Simmer K, Nagarajan L. Intravenous levetiracetam for treatment of neonatal seizures. J Clin Neurosci. 2013;20(8):1165-7.

Tulloch JK, Carr RR, Ensom MHH. A Systematic Review of the Pharmacokinetics of Antiepileptic Drugs in Neonates with Refractory Seizures. J Pediatr Pharmacol Ther. 2012;17(1):31-44.