Is Levetiracetam an Effective First-line Treatment for Neonatal Seizures?

Pavankumar Kamat


July 01, 2021


  • Levetiracetam may not be more effective than phenobarbital in achieving seizure cessation when used as the first-line treatment for neonatal seizures.

  • However, levetiracetam had a better short-term safety profile than phenobarbital.

Why this matters

  • Findings suggest that seizure aetiology and continuous electroencephalogram monitoring should be considered while planning future trials on antiseizure medications.

Study design

  • UK researchers conducted a meta-analysis of 14 studies (4 randomised controlled trials [RCTs]; 10 observational trials) including 1188 neonates.

  • Primary outcome: seizure cessation within 24 hours of levetiracetam administration.

  • Secondary outcomes: short-term adverse events, mortality before discharge and long-term neurodevelopmental outcomes.

  • Funding: None.

Key results

  • Pooled results of observational trials showed that 45% (95% CI, 34-57%) of neonates responded to levetiracetam when used as a first-line antiseizure treatment.

  • Pooled results of RCTs showed that levetiracetam and phenobarbital were equally effective in achieving seizure control (risk ratio [RR], 0.60; 95% CI, 0.30-1.20; I2, 93%).

  • Levetiracetam vs phenobarbital was associated with a lower risk of short-term adverse events (3 RCTs; RR, 0.24; 95% CI, 0.06-0.92; I2, 69%).

  • No significant differences were seen between levetiracetam and phenobarbital groups in (RR; 95% CI):

    • mortality before discharge (4 RCTs; 0.82; 0.41-1.63); and

    • long-term neurodevelopmental outcomes (2 RCTs; 0.68; 0.08-6.01).


  • Heterogeneity among studies.


Hooper RG, Ramaswamy VV, Wahid RM, Satodia P, Bhulani A. Levetiracetam as the first-line treatment for neonatal seizures: a systematic review and meta-analysis. Dev Med Child Neurol. 2021 Jun 13 [Epub ahead of print]. doi: 10.1111/dmcn.14943. PMID: 34124790.  View abstract .

This clinical summary originally appeared on Univadis, part of the Medscape Professional Network.


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