Levetiracetam Outweighs Common Therapies for Pediatric Epilepsy

A comparison of 2 drugs commonly prescribed for infants with nonsyndromic epilepsy (NSE) found that oral anticonvulsant therapy levetiracetam significantly reduces treatment regiment and seizure rates when compared to phenobarbital.

A multicenter cohort study of 155 infants with NSE provided the first evidence that one common initial pediatric therapy for non-conforming epilepsy is significantly more beneficial than the other.

Anne T. Berg, PhD, from Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago, told MD Magazine that although levetiracetam is already far and away the preferred initial therapy for children suffering from NSE, this is substantial analysis showing that it is superior to the next-prescribed therapy in managing short-term seizures.

The study compared the 2 therapies as initial monotherapies in 155 children with NSE with seizure onset at 1 month to 1 year of age. Researchers administed levetiracetam to 117 patients, and phenobarbital to 38 patients for 6 months.

About 40% of infants receiving levetiracetam did not require an additional anti-epileptic therapy to help control seizures, and became seizure-free within 3 months of initial of initial therapy. Just 16% of the patients treated with phenobarbital reached the same outcome.

Although the patient population for levetiracetam were 2 months older at the time of seizure onset than the phenobarbital population, (median, 5.2 months [IR, 3.5-8.2 months] versus 5 months [IR, 2.0-4.4 months]; P < 0.001), and also tended to begin treatment later after their first seizure, there were no other clinically important differences in the patient groups.

Because the research was not conducted as a randomized trial, researchers called for a follow-up prospective clinical trial. Berg added that she would hope for a long-term analysis of the 2 therapies, noting that while short-term seizures are “not a bad gauge” for infants with NSE, there are behavioral and developmental effects linked to both common drugs.

“There are several things at stake,” Berg said. “The seizures, especially in a developing brain, seem to have an enduring negative impact on reaching certain milestones that leads to mental cognition impairment. Getting those seizures under control early is very much so worth it.”

Berg said phenobarbital’s reputation among physicians and patients is aided by its history — its century-plus usage as an anticonvulsant lends to the notion that it’s a safer option. However, its link to psychiatric effects after therapy’s end is known.

“I’d like to see children followed systematically with seizure logs by both physicians and parents — not just for seizures, but for behavior because both drugs have behavioral effects,” Berg said. “Phenobarbital has a proven effect on psychiatric conditions after its end.”

The true value of the study may come from its network building. The involved 17 medical centers, all from the US Pediatric Epilepsy Research Consortium, have been conglomerated since 2012, and is looking to emulate the extensive research found in other cooperative groups such as the Children’s Oncology Group, Berg said.

Other comparative effectiveness research papers will come out of this study, which served as a demonstration of pediatric epilepsy centers working together in a culture of networked researchers. Larger studies may eventually follow.

The study, "Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy," was published online in JAMA Pediatrics Monday.

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