Management of epilepsy in childhood presents numerous potential clinical challenges, not the least of which is selection of an optimal therapeutic regimen. While AED monotherapy is successful in some cases, many patients will be treated with at least two AEDs. Some pediatric patients with intractable seizures are treated with three or more AEDs. However, the addition of a third anticonvulsant may have limited benefit in seizure management, recent research published in Journal of Child Neurology reveals.1

What is the likelihood of benefit for adding a second or third AED in pediatric patients with uncontrolled epilepsy?
“The likelihood of controlling childhood epilepsy with addition of a second agent is high but this is not the case when a third agent is serially added,” explains lead study author Jay Desai, MD, of the Department of Pediatric Neurology, Children's Hospital Los Angeles. “However, this is not zero.”

The recently-published retrospective chart review of 84 children with intractable epilepsy at one clinic found that a majority of patients (35 of 52) had a reduction in seizure frequency of 50 percent or more when a second AED was added to their regimen. But only five of 30 patients had a ≥50 percent reduction in seizure frequency when a third AED was added. “This finding obviously would help counsel the parents and/or patients about what to expect with serial addition of AEDs,” Dr. Desai says.

Clinicians and patients seek to obtain the best possible seizure control with the fewest therapeutic agents. While not a focus of his study, Dr. Desai notes that combined use of multiple AEDs can increase the risk for drug interactions and common neurocognitive side effects associated with this class of drugs, such as drowsiness and behavioral changes.

What implications for patient care may derive from the study?
Given that the addition of a third AED seems to have minimal potential to improve seizure control, neurologists may have to carefully assess the management of the pediatric patient who is not well controlled on two agents. Currently, guidance is limited.

“We need better studies and guidelines addressing the following question keeping risks and benefits in mind: Which strategy is better in medical management of difficult to control childhood epilepsy—to taper one of the two AEDs while adding another one or serially add a third agent?,” Dr. Desai says. “There are no guidelines available to my knowledge to date.” He encourages prospective, multi-center trials to elucidate an ideal management strategy.

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