BALTIMORE — Megan Ephage lives in fear of another big epileptic seizure. The 22-year-old Glen Burnie, Md., woman had her first seizure when she was 13. Even though medications largely keep her epilepsy under control, the prospect of seizures means she can't drive, which makes it difficult getting to classes at Anne Arundel Community College. She dreams of becoming a lawyer, but keeping a job is a challenge. She said her last employer in a retail store feared her disorder.
New research on the best way to administer drugs that stop seizures could prove life-changing, as well as life-saving, for Ephage and others.
Paramedics know what drugs stop these damaging and potentially fatal seizures, but they have had trouble getting them into the veins of their convulsing patients. Now paramedics and doctors in Maryland and across the country have helped show that the drugs can be easily delivered into the thigh muscle using an injector similar to the EpiPen carried by those with serious allergic reactions.
"This validates the safety and effectiveness of the shot," said Dr. Tricia Ting, an assistant professor of neurology at the University of Maryland Medical Center, one of 17 academic centers pursuing the best method of stopping "status epilepticus," or prolonged seizures that cause 55,000 deaths a year.
That is what the National Institute of Neurological Disorders and Stroke at the National Institutes of Health aimed to discover when it initiated the study in 2009.
The situation, officials say, was pressing: More than 1 percent of the U.S. population has epilepsy, or more than 3 million people, and while most of their seizures do not last longer than a minute and do not require medical attention, prolonged seizures lasting more than 5 minutes can cause brain damage and death.
About 275,000 people have such prolonged seizures annually, and up to 20 percent die when the seizures aren't stopped, researchers say.
Authorities have assumed that drugs given through veins rather than muscles are absorbed more quickly. But in this study, led by University of Michigan researchers and published Feb. 16 in the New England Journal of Medicine, intramuscular injections worked better than the intravenous ones. Seizures had stopped in more people by the time they arrived at the hospital.
Eventually, the researchers say, they expect patients and their families to be able to carry an injector pen and administer the drug themselves.
Having a pen in her pocket might just give everyone some peace of mind, Ephage said.
"I'd like to carry it around or have someone carry it for me," she said. "A serious seizure wouldn't be as serious because everyone would know it could be stopped. ... Now everyone is scared something will happen. I think it's unfair.
The epilepsy pen injects midazolam, the drug already used by Maryland paramedics, though they typically administer it intravenously. Other emergency personnel around the nation use another drug, called lorazepam. It can only be given intravenously, it requires refrigeration, and ambulances in the state and elsewhere are not yet equipped with such equipment.
Officials report that both drugs cost about $3 to $5 a dose, though most emergency medical service agencies get them more cheaply. But midazolam has a longer shelf life, potentially saving the agencies money.
During the study, 4,000 paramedics around the country were instructed to give each patient having prolonged seizures both intramuscular and intravenous therapy from specially prepared boxes; the paramedics and patients did not know which one contained the drug and which one contained a placebo. A time-stamped voice recorder took down how long the medication took to work and researchers followed up to see if patients needed to be admitted to the hospital after treatment in the emergency room.
The goal was to stop the seizures within 10 minutes without having to administer more drugs. Sometimes prolonged seizures can last for hours, stopping only with a dose of general anesthesia.
Based on nearly 900 patients, the study found seizures had stopped in 73 percent of those receiving midazolam in the thigh by the time they reached the hospital, compared to 63 percent of those who got lorazepam in a vein. The midazolam patients were also less likely to require hospitalization, and recurrent seizures were low in both groups if they were admitted.
Unlike most randomized clinical trials, this one did not seek permission from patients for their participation because their situations were emergencies. Instead, the University of Maryland's Ting said, researchers around the country reached out to the epilepsy community and the public in advance to discuss the study. She said most people seemed supportive of finding the best drug delivery method.
Other clinical trials, perhaps for strokes and traumatic brain injury, are expected to be conducted in the future using the same framework.
Dr. Robert Bass, executive director of the Maryland Institute for Emergency Medical Services Systems, which oversees the state's paramedics, said that patients in this study and future ones still receive the accepted treatment at the same time they help with the research that may benefit them.
Officials at the U.S. Departments of Defense and Health and Human Services, which helped fund the study, also learned that they may be able to manage large numbers of seizures caused by chemical attacks with intramuscular shots.
Bass believes the thigh shots may have come out ahead because paramedics needed more time to administer the drugs intravenously. But the findings are probably enough to persuade officials to switch to the method.
That won't be until 2013, though. The next set of protocols, which go into effect in July, has already been vetted and written.
"It's one study, but it's a good study," Bass said. "I think this will have influence. ... I think most paramedics would prefer the method."
Some paramedics around the country have already been using shots to the thigh, particularly if they can't get IV access, said Dr. Alan Ettinger, a member of the board of the Epilepsy Foundation who was not involved in the study. He said this will "give them confidence in the practice."
More paramedics, and even emergency room doctors, are likely to switch, said Ettinger, who is also the epilepsy director at Neurological Surgery PC, a private neurosurgery practice in Long Island, N.Y.
He said timely administration of drugs can make a big difference in preserving brain function and life. But unlike stroke victims who need timely clog-busting medications for effective treatment, the window for those having a seizure never closes.
And while sufferers would benefit from this study, and eventually a pen in their pockets, he also advocated for more public understanding of the disorder. Regular treatment controls seizures for most people with epilepsy, defined as those who have had two or more seizures, he said.
"Even if a patient has seizures, most stop on their own and there is no need for an employer or anyone to administer emergency therapy," Ettinger said. "And the good news is most don't have prolonged seizures, and when they do, we have effective treatments."