Reach for Levetiracetam in Early-Onset Nonsyndromic Epilepsy?

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Most US children with early onset, nonsyndromic epilepsy are initially treated with levetiracetam monotherapy, according to new study in Pediatric Neurology.¹

“Although there are many available medications for early-life epilepsy treatment, and little evidence that any individual medication has superior efficacy compared with the others, our data suggest that the pediatric neurology community in the United States appears to have reached an informal consensus on the initial treatment of early-life epilepsies,” wrote first author Renee Shellhaas, MD, of the University of Michigan, Ann Arbor, Michigan, and colleagues.

The findings suggest a standard practice could be emerging despite lack of guidelines-or even opinion recommendations-about the preferred approach to treating early-onset (before age 3 years) nonsyndromic epilepsy. Lack of guidance is related to the dearth of evidence in this population. Among 20 antiepileptic drugs (AEDs) now available, little evidence exists to support one over the other in children.

To evaluate what’s happening in clinical practice, researchers did a prospective cohort study at 17 tertiary academic medical centers in the US. The study took place from January 2013 to March 2015, and used chart review to extract medical record data for 495 children younger than 36 months with new-onset nonsyndromic epilepsy. No attempt was made to standardize care or influence medication selection, dosing, or management among treating physicians.

Key results:
• 464 children were treated with AED monotherapy
• 74% of children received levetiracetam either as first- or second line therapy within the first year after diagnosis
   o First line: 63% received levetiracetam, followed by oxcarbazepine (14%), phenobarbital (12%), topiramate (3.4%), and zonisamide (2.8%)
   o Levitiracetam was most commonly prescribed regardless of epilepsy type (focal, generalized, mixed/uncertain)
• Initial treatment varied by age:
   o 31% of infants under 6 months received phenobarbital first
   o 2.3% of children over age 6 months received phenobarbital first (p<0.0001)

The authors emphasized that early life epilepsy can have serious consequences on neurodevelopment. At the same time, concerns have been raised about the effect of AEDs on brain development. Although results suggest levetiracetam is most frequently prescribed, the authors stressed that the results do not necessarily mean the drug is superior for seizure control, quality of life, and developmental outcomes.  Reasons for its popularity could include: availability in liquid form, lack of drug interactions, and ability to be given intravenously.

They also pointed out that a shift has occurred in treating early onset pediatric epilepsy: away from carbamazepine and valproic acid in the 1990s and toward newer drugs like levetiracetam.  This change has happened despite little evidence regarding pharmacokinetics, efficacy, or long-term effects of treatment.

They concluded: “Although it remains unclear if a shift toward treatment with this broad-spectrum medication will result in improved outcomes, it appears that the stage is ready for comparative effectiveness studies that could lead to standardization and optimization of the use of current drugs and prepare the way for future trials of novel therapies.”

Take Home Points:
• Study found that levetiracetam monotherapy is most commonly prescribed as first-line therapy in US children diagnosed with nonsyndromic epilepsy before age 36 months
• Results suggest an unexpected consensus is emerging in the pediatric neurology community, despite lack of guidelines, opinion recommendations, and research on initial treatment for early onset nonsyndromic epilepsy
• Comparative effectiveness studies are needed to evaluate which AED improves outcomes in early onset nonsyndromic epilepsy, and to support standardization of care

References:

1. Shellhaas RA, Berg AT, Grinspan ZM, et al. Initial treatment for nonsyndromic early-life epilepsy: an unexpected consensus. Pediatr Neurol. 2017 Oct;75:73-79.