Head-to-head comparison finds three anti-seizure drugs equally effective for severe form of epilepsy

November 27, 2019

ANN ARBOR, Mich. - A new study finds that the three most common treatment options administered in the emergency department for patients who experience refractory status epilepticus are equally safe and effective.

Status epilepticus is characterized by individual seizures or multiple seizures close together lasting more than five minutes with a loss of consciousness. If not treated, it can lead to severe brain damage or death.

Benzodiazepines, a class of sedating medications that target the central nervous system, are the first line of treatment for status epilepticus and are effective in two-thirds of patients. Refractory status epilepticus occurs in those patients in whom benzodiazepines don't stop their seizures.

"Optimizing emergency treatment with benzodiazepines has previously proven to reduce intensive care unit stays, hospitalization and other complications, but we have not had clinical trial data to tell us what works in those patients who continue to seize despite benzodiazepines," says Robert Silbergleit, M.D., a professor of emergency medicine at Michigan Medicine.

"Although levetiracetam, fosphenytoin and valproate are three of the most commonly used intravenous drugs to treat refractory status epilepticus in both children and adults, before this study, we didn't know if one of these drugs worked better, or if any of them worked well at all."

Silbergleit is the senior author of the new study, published in the New England Journal of Medicine, which reveals the three drugs are equally safe and effective in treating patients with refractory status epilepticus. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"Doctors can be confident that the particular treatment they choose for their patients with status epilepticus is safe and effective and may help them avoid the need to intubate the patient as well as stays in the intensive care unit," says Robin Conwit, M.D., NINDS program director and an author of the study.

"This was a truly collaborative, multidisciplinary study that involved pediatricians, emergency medicine doctors, neurologists, pharmacologists and biostatisticians all contributing their expertise."

Trial results

In the Established Status Epilepticus Treatment Trial (ESETT), more than 380 children and adults were randomized to receive levetiracetam, fosphenytoin or valproate when they came to the emergency department experiencing prolonged seizures.

Silbergleit, along with lead co-authors Jordan Elm, Ph.D., a professor at Medical University of South Carolina, James Chamberlain, M.D., a professor at George Washington University and Jaideep Kapur, M.B., B.S., Ph.D., a professor at the University of Virginia, hoped to determine which of the anticonvulsant drugs was most effective in stopping seizures and improving a patient's level of responsiveness within 60 minutes of administering treatment.

The results showed that the three drugs stopped seizures and improved responsiveness in approximately half of the study participants. Specifically, these benefits were seen in 47% of subjects in the levetiracetam group, in 45% of participants in the fosphenytoin group and in 46% of subjects in the valproate group. These differences weren't statistically significant and there were no differences in serious side effects among the drugs.

"Our study suggests that clinical outcomes are driven by factors other than drugs," Silbergleit says.

"Differences in how doctors decide to treat status epilepticus, such as when they give more drugs or when to anesthetize patients and put them on a mechanical ventilator, may be more important than the specific treatments used to control seizures in patients."

The study was stopped early when a planned interim analysis found that the drugs were equally safe and effective.

The ESETT researchers utilized a clinical trial design known as response adaptive randomization to improve the study's efficiency and maximize the chances of identifying the best treatment. The study used an algorithm to determine which drugs patients would receive based on accumulating trial data.

"Using an innovative design for this clinical trial, we were able to answer this important question in a timely and cost-effective manner," Kapur says. "In addition, this design lowered risk by reducing the chances that participants could have received what might have been determined to be the least effective treatment."

Future use

Silbergleit notes that the results of ESETT validate the use of the three drugs and give emergency physicians options when it comes to treating patients with refractory status epilepticus.

"Of the three medications tested, only fosphenytoin is labeled by the Food and Drug Administration as a treatment for status epilepticus, and it is only approved for status epilepticus in adult patients," he says.

"Our results demonstrate that doctors can choose a treatment based on availability, as shortages of these drugs have been common in recent years, cost, ease of administration or other practical criteria."

Additional research is needed to prevent refractory status epilepticus and to find treatment options for the patients whose seizures don't respond to the three drugs investigated in this study.
-end-
This study was supported by the NINDS (U01NS088034, U01NS088023, U01NS056975, U01NS059041, and U01NS073476).

This press release was adapted from the NINDS press release on the study.



Michigan Medicine - University of Michigan

Related Seizures Articles from Brightsurf:

Hallucinations in people with seizures may point to suicide risk
A study from scientists at Trinity College Dublin and Royal College of Surgeons in Ireland shows that 8% of individuals with a history of seizures report hallucinations, including experiences of hearing or seeing things that are not based in reality.

Epilepsy: Seizures not forecastable as expected
Epileptic seizures can probably not be predicted by changes in brain wave patterns that were previously assumed to be characteristic precursors.

Predicting epileptic seizures might be more difficult than previously thought
By studying the brain dynamics of 28 subjects with epilepsy, scientists demonstrated there is no evidence for a previously suspected warning sign for seizures known as 'critical slowing down,' which refers to characteristic changes in the behavior of a complex system that approaches a theoretical tipping point; when this point is exceeded, there can be impactful and devastating changes.

Gene protective against fruit fly heat-induced seizures may explain some human seizures
Researchers identified a gene in fruit flies that helps prevent the hyperexcitability of specific neurons that trigger seizures.

Rethinking seizures associated with cardiac disease
Research from Washington University in St. Louis finds that mutations of a gene implicated in long QT syndrome in humans may trigger seizures because of their direct effects on certain classes of neurons in the brain -- independent from what the genetic mutations do to heart function.

UTSA reduces seizures by removing newborn neurons
Epileptic seizures happen in one of every 10 people who have experienced a traumatic brain injury (TBI).

Reducing seizures by removing newborn neurons
Removing new neurons born after a brain injury reduces seizures in mice, according to new research in JNeurosci.

Inducing seizures to stop seizures
Surgery is the only way to stop seizures in 30 per cent of patients with focal drug-resistant epilepsy.

New research could help predict seizures before they happen
A new study has found a pattern of molecules that appear in the blood before a seizure happens.

New drug could help treat neonatal seizures
A new drug that inhibits neonatal seizures in rodent models could open up new avenues for the treatment of epilepsy in human newborns.

Read More: Seizures News and Seizures Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.