Despite lack of efficacy data, surprising consensus in pediatric anti-epilepsy med scripts

July 19, 2017, Children's National Medical Center
William D. Gaillard, M.D., division chief of Child Neurology and Epilepsy, Neurophysiology and Critical Care Neurology at Children's National Health System. Credit: Children's National Health System

The number of available anti-seizure medications has exploded in the past two decades, going from just a handful of medicines available in the 1990s to more than 20 now. Once the Food and Drug Administration (FDA) approves each new medicine based on trials in adults, it's available for clinicians to prescribe off-label to all age groups. However, says William D. Gaillard, M.D., division chief of Child Neurology and Epilepsy, Neurophysiology and Critical Care Neurology at Children's National Health System, trials that lead to FDA approval for adults do not provide any information about which medications are best for children.

"With so many medications and so little data," Dr. Gaillard says, "one might think doctors would choose a wider variety of medicines when they prescribe to children with ."

However, the results from a recent study by Dr. Gaillard and colleagues, published online in Pediatric Neurology on June 27, 2017, show otherwise. The study indicates that doctors in the United States appear to have reached an unexpected consensus about which to prescribe for their pediatric patients.

The study is part of a broader effort to collect data on the youngest epilepsy patients—those younger than 3 years old, the age at which epilepsy most often becomes evident. As part of this endeavor, researchers from 17 U.S. pediatric epilepsy centers enrolled in the study 495 children younger than 36 months old who had been newly diagnosed with non-syndromic epilepsy (a condition not linked to any of the commonly recognized genetic epilepsy syndromes).

The researchers mined these patients' electronic medical records for information about their demographics, disease and treatments. About half of the study participants were younger than 1 year old when they were diagnosed with epilepsy. About half had disease marked by focal features, meaning that their epilepsy appeared to originate from a particular place in the brain. Nearly all were treated with a single medication, as opposed to a cocktail of multiple medicines.

Of those treated with a single medication, nearly all were treated with one of five medicines: Levetiracetam, oxcarbazepine, phenobarbital, topiramate and zonisamide. However, the data showed a clear prescribing preference. About 63 percent of the patients were prescribed levetiracetam as a first choice. By contrast, oxcarbazepine and phenobarbital, the next most frequently prescribed medicines, were taken by patients as a first choice by a mere 14 percent and 13 percent respectively.

Even more striking, of the children who were not prescribed levetiracetam initially but required a second medication due to inadequate efficacy or unacceptable side effects, 62 percent also received this medication. That made levetiracetam the first or second choice for about 74 percent of all the children in the study, despite the availability of more than 20 anti-seizure medications.

It's not clear why levetiracetam is such a frequent choice in the United States, says Dr. Gaillard. However, in its favor, the drug is available in a liquid formulation, causes no ill effects medically and can be started intravenously if necessary. Studies have shown that it appears to be effective in controlling seizures in about 40 percent of infants.

Yet, levetiracetam's market dominance appears to be a North American phenomenon, the study authors write. A recent international survey that Dr. Gaillard also participated in suggests that outside of this continent, carbazepine and oxcarbazepine were the most frequently prescribed medications to treat focal seizures.

What's really necessary, Dr. Gaillard says, is real data on efficacy for each of the medications commonly prescribed to pediatric epilepsy patients—a marked vacuum in research that prevents doctors from using evidence-based reasoning when making medication choices.

"This study identifies current practices, but whether those practices are correct is a separate question," he explains. "Just because a medication is used commonly doesn't mean it is the best medication we should be using."

To answer that question, he says, researchers will need to perform a head-to-head clinical trial comparing the top available epilepsy medications in children. This study sets the stage for such a trial by identifying which medications should be included.

"Uncontrolled can have serious consequences, from potential problems in development to a higher risk of death," Dr. Gaillard says. "You want to use the optimal to treat the disease."

Explore further: Study examines self-management intervention in patients with epilepsy

More information: Renée A Shellhaas et al, Initial Treatment for Non-Syndromic Early-Life Epilepsy: an Unexpected Consensus, Pediatric Neurology (2017). DOI: 10.1016/j.pediatrneurol.2017.06.011

Related Stories

Study examines self-management intervention in patients with epilepsy

June 7, 2017
A new study has found that a multi-component self-management intervention (MCI) for adults with epilepsy may be an important tool to increase efficiency in epilepsy care.

Good news for kids with epilepsy

February 27, 2017
There's good news for kids with epilepsy. While several new drugs have come out in the last several years for adults with epilepsy, making those drugs available for children and teenagers has been delayed due to the challenges ...

No link to lower IQs in children of mothers who have taken newer forms of epilepsy drugs

August 31, 2016
Two newer epilepsy drugs may not harm the thinking skills or IQs of school-aged children whose mothers took them while pregnant - but an older drug is linked to cognitive problems in children, especially if their mothers ...

Patient should talk to doctor about interest in discontinuing anti-epileptic medication

April 8, 2016
Dear Mayo Clinic: I was diagnosed with epilepsy three years ago at the age of 29. I've been on medication since then and haven't had another seizure. Is it true that, for some people, epilepsy is not necessarily a lifelong ...

New guideline published on uncommon risk of death in epilepsy

April 25, 2017
There is an uncommon risk of death that people with epilepsy and their loved ones may not know about. The risk is called sudden unexpected death in epilepsy, or SUDEP. Now the American Academy of Neurology (AAN) and the American ...

Recommended for you

How do we lose memory? A STEP at a time, researchers say

March 23, 2018
In mice, rats, monkeys, and people, aging can take its toll on cognitive function. A new study by researchers at Yale and Université de Montréal reveal there is a common denominator to the decline in all of these species—an ...

Brain's tiniest blood vessels trigger spinal motor neurons to develop

March 23, 2018
A new study has revealed that the human brain's tiniest blood vessels can activate genes known to trigger spinal motor neurons, prompting the neurons to grow during early development. The findings could provide insights into ...

Being hungry shuts off perception of chronic pain

March 22, 2018
Pain can be valuable. Without it, we might let our hand linger on a hot stove, for example. But longer-lasting pain, such as the inflammatory pain that can arise after injury, can be debilitating and costly, preventing us ...

From signal propagation to consciousness: New findings point to a potential connection

March 22, 2018
Researchers at New York University have discovered a novel mechanism through which information can be effectively transmitted across many areas in the brain—a finding that offers a potentially new way of understanding how ...

Using simplicity for complexity—new research sheds light on the perception of motion

March 22, 2018
A team of biologists has deciphered how neurons used in the perception of motion form in the brain of a fly —a finding that illustrates how complex neuronal circuits are constructed from simple developmental rules.

Focus on early stage of illness may be key to treating ALS, study suggests

March 22, 2018
A new kind of genetically engineered mouse and an innovation in how to monitor those mice during research have shed new light on the early development of an inherited form of amyotrophic lateral sclerosis (ALS).


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.