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December 10, 2019
Drugs equally effective for severe seizure disorder
At a Glance
- Three commonly prescribed anti-seizure drugs worked equally well for patients with seizures who did not respond to benzodiazepines.
- The findings could inform emergency room decisions for patients with a severe form of epilepsy called refractory status epilepticus.
Status epilepticus is a form of epilepsy in which seizures last for at least five minutes or occur one after another without regaining consciousness. If not treated, it can lead to severe brain damage or death.
Benzodiazepines are the first type of medication used by emergency room doctors for status epilepticus. However, up to a third of patients don’t respond to the drugs. This condition is known as refractory status epilepticus. Three anti-seizure medications—fosphenytoin, levetiracetam, or valproate—are commonly used to treat these patients, but little research had been done to compare them.
Researchers enrolled patients at 57 emergency rooms across the nation to determine which of these medications was most effective for treating refractory status epilepticus. The trial was led by Drs. Jaideep Kapur of the University of Virginia; Robert Silbergleit of the University of Michigan, Ann Arbor; Jordan Elm of the Medical University of South Carolina; and James Chamberlain of the George Washington University.
The study was funded by NIH’s National Institute of Neurological Diseases and Stroke (NINDS). Results appeared in the New England Journal of Medicine on November 28, 2019.
Almost 400 children and adults were randomly assigned to receive one of the three drugs when they came to the emergency room experiencing seizures. Only fosphenytoin is approved by the Food and Drug Administration (FDA) for treating refractory status epilepticus, and none of the drugs is approved for children. All three medications are delivered intravenously.
Researchers used an algorithm to determine which drugs patients would receive based on trial data as it accumulated. This clinical trial design is known as response adaptive randomization. It improves efficiency and maximizes the chances of identifying the best treatment.
The research team found that the three medications were equally effective. All stopped seizures and improved responsiveness within an hour for about half of the patients: 45% in the fosphenytoin group, 47% in the levetiracetam group, and 46% in the valproate group. There were no differences in serious side effects among the drugs, either.
The study was stopped early because an analysis found that the data already showed the three drugs were equally safe and effective.
“Our study suggests that clinical outcomes are driven by factors other than drugs. 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,” Silbergleit says.
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References: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. Kapur J, Elm J, Chamberlain JM, Barsan W, Cloyd J, Lowenstein D, Shinnar S, Conwit R, Meinzer C, Cock H, Fountain N, Connor JT, Silbergleit R; NETT and PECARN Investigators. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. PMID: 31774955.
Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS)