Literature Review

Levetiracetam May Be Superior to Phenobarbital for Infantile Epilepsy

Missing data may have influenced the analysis, and further research is needed.


Levetiracetam may be a superior initial treatment for infants with nonsyndromic epilepsy, according to a multicenter, prospective, observational study published online ahead of print February 12 in JAMA Pediatrics.

“Our findings suggest that levetiracetam has superior effectiveness, compared with phenobarbital, as initial monotherapy for nonsyndromic epilepsy in infants,” said Zachary Grinspan, MD, Director of the Pediatric Epilepsy Program at Cornell University, New York, and colleagues. “We estimate that for every 100 infants with epilepsy treated with levetiracetam instead of phenobarbital, 44 infants would be free from monotherapy failure instead of 16.”

Zachary Grinspan, MD

To evaluate the effectiveness of levetiracetam vs phenobarbital, the researchers conducted the Early Life Epilepsy Study, which included 155 children with nonsyndromic epilepsy. Patient information was obtained from medical records and collected from March 1, 2012, through April 30, 2015. All participants were observed during their first three years of life.

In all, 117 children were treated with levetiracetam, and 38 with phenobarbital. Children treated with levetiracetam were, on average, two months older at seizure onset than were those in the phenobarbital group (5.2 months vs 3.0 months). Infants treated with levetiracetam also tended to begin treatment further from the time of their first seizure and exhibited less developmental delay at the time of epilepsy diagnosis.

Freedom from monotherapy failure was more common in the levetiracetam group than the phenobarbital group (40.2% vs 15.8%).

Outcome information was missing for more infants treated with levetiracetam than those treated with phenobarbital, which could have influenced the analyses, said Dr. Grinspan. The genetic interactions that influence nonsyndromic epilepsy make the latter difficult to study.

Although this study provides information that could benefit patients with infantile epilepsy, more work must be done on the topic, said the investigators. “A prospective clinical trial is needed. Levetiracetam and phenobarbital are both commonly used for infantile-onset epilepsy, indicating community equipoise regarding their relative effectiveness,” they said. “However, the effect size in our analysis was surprisingly large (number needed to treat, 3.5), suggesting that a change in practice could meaningfully improve outcomes.”

—Ian Lacy

Suggested Reading

Grinspan ZM, Shellhaas RA, Coryell J, et al. Comparative effectiveness of levetiracetam vs phenobarbital for infantile epilepsy. JAMA Pediatr. 2018 Feb 12 [Epub ahead of print].

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