Research
Could anti-depressants help reduce the risk of Sudden Death in Epilepsy?
Written by Karen Carlson
Dr. Carl Faingold, professor and chair of the Department of Pharmacology,has published what is being called “a groundbreaking study” that provides evidence that a category of antidepressant drugs known as Selective Serotonin Reuptake Inhibitors (SSRIs) may reduce the risk of Sudden Unexpected Death in Epilepsy (SUDEP). The study was published in Elsevier’s Epilepsy & Behavior in October 2011.
SUDEP is estimated to be the cause of death in up to 17 percent of patients with epilepsy who die from their ondition.One high-profile case was actor John Travolta’s son, Jett, who died in 2009. Evidence for cardiac and respiratory causes of SUDEP has been presented, but no effective prevention of SUDEP has yet been developed.
During an epileptic seizure, carbon dioxide levels can rise, which may be a contributing cause of sudden death. The neurotransmitter serotonin may help to enhance respiration in response to the elevated levels of carbon dioxide and reduce the incidence of death. “The SSRIs improve depression by increasing the amount and prolonging the effect of serotonin on neurons,” Dr. Faingold said.
His study evaluated whether administration of the antidepressant fluoxetine, (commonly known as Prozac®) would be effective in preventing sudden death in a strain of mice known to be susceptible to respiratory arrest during epileptic seizures.
The study found that a semi-chronic (5-day) treatment with a low-dose of fluoxetine may be a useful approach to prevent sudden death by preventing respiratory arrest. This effect was temporary, and susceptibility to sudden death returned 1-3 days after fluoxetine treatment. Dr. Faingold’s lab is planning future studies with other SSRIs and other selective 5-HT agonists, as well as longer-term treatment paradigms.
Dr. Faingold’s colleagues have commended this study. “The findings in [Dr. Faingold’s] study are very important because they reveal very specific mechanisms that could explain the impaired breathing that is known to occur with seizures in many persons with epilepsy,” noted Elson L. So, M.D., second vice-president of the American Epilepsy Society and professor of neurology at Mayo Clinic College of Medicine. “Studies along this line may eventually lead to the use of currently available medicines in persons with poorly controlled seizures to reduce their risk for SUDEP.”
Dr. George Richerson, chairman of neurology at the University of Iowa and an expert on 5-HT, breathing and SUDEP said, “This paper is a major advance because it shows in a well-validated animal model that semi-chronic treatment with a safe and widely used drug can prevent both respiratory arrest and sudden death. Although this does not directly prove that this approach would be effective in humans, it provides a strong rationale for clinical trials to prevent the most common cause of death in epilepsy patients, which has previously been unpreventable.”
“This is a significant development in SUDEP research. Not one more life should be lost to epilepsy; it’s studies like this that will make that dream a reality,” said Jeanne Donalty member of the CURE Board of Directors for Citizens United for research in Epilepsy (CURE). Dr. Faingold’s research was sponsored by CURE.
“Dr. Faingold and colleagues have made a very important observation which, with further study, holds the promise for the development of treatments to lessen the risk of the devastating problem of SUDEP,” said Steven C. Schachter, M.D., professor of neurology at Harvard Medical School and editor-in-chief of Epilepsy & Behavior.
Dr. Faingold has studied epilepsy and alcoholism for more than 30 years. He has received funding from the National Institutes of Health and other national foundations. He has more than 100 publications to his credit.
“I see this as the culmination of 30 years of work,” Dr. Faingold said. “Up until now, my work has been theoretical, understanding how seizures are induced. This study gives us an exciting new direction that combines neuroscience’s study of the brain’s control of respiration, which has shown that serotonin is important in maintaining breathing, and studies of epilepsy.”
Following the publication of Dr. Faingold’s research, a group at the University of California-Davis did a retrospective study of patients in its epilepsy-monitoring unit who all showed repressed respiration. They found that SSRI-treated patients had a lower degree of respiration depression than in non-SSRI treated patients. That group is now planning a prospective study. Another major retrospective study is being planned in Sweden to see if there is a difference in SUDEP outcomes using an SSRI.