Public Release: 

Anti-convulsant drug significantly reduced major depression symptoms

Findings could result in new therapies to treat depression

The Mount Sinai Hospital / Mount Sinai School of Medicine

NEW YORK, NY (November 1, 2018) Researchers from the Icahn School of Medicine at Mount Sinai found that patients with Major Depressive Disorder (MDD) exhibited a significant reduction of depressive symptoms after being treated with ezogabine, an FDA approved drug used to treat seizures.

After treatment, patients showed a 45 percent reduction in depression, a significant reduction in anhedonia, the inability to feel pleasure; and a significant increase in resilience.

This is the first study to suggest that ezogabine, part of a class of drugs known as potassium channel openers, may have an antidepressant affect in humans.

The review will be published online on Thursday November 1st at 9AM EST , in Molecular Psychiatry.

Major depressive disorder (MDD) impacts 15 million Americans and is the leading cause of disability, yet current treatments possess limited efficacy. A new therapeutic direction is emerging from the increased understanding of natural resilience as an active stress-coping process. It is known that potassium channels in the brain's reward system are an active mediator of resilience.

In a previous study, the Mount Sinai research team tested ezogabine, also known as retigabine, a potassium channel opener, in mice. They found that that ezogabine had significant antidepressant effects in the mice, expressed by two common measures in rodents: increased social interactions and preferences for natural rewards.

In this study, 18 medication free individuals with MDD experiencing a major depressive episode received up to 900 mg of ezogabine daily during 10 weeks in an open label study to determine if the drug significantly engaged their reward system. Resting state functional magnetic resonance imaging data revealing the connectivity of the reward system were collected at baseline and post-treatment to reexamine brain reward circuitry. After treatment with ezogabine, subjects exhibited a significant reduction of depressive symptoms measured by the the change in connectivity of their reward system.

"The results of this study are exciting because we haven't had a new medicine to treat depression in decades," said the study's senior author, James Murrough, MD, PhD, Director of the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai. "Most antidepressants are in the same class of drugs and work by increasing serotonin. Our research suggests a different molecular target that works through other brain mechanisms and could be helpful for patents."

The research team at Mount Sinai is currently conducting a larger multi-site double blind trial of ezogabine in patients with depression funded by the National Institute of Mental Health to further determine its efficacy in treating depression.

"We know that patients with depression become depressed for different reasons, and we've been stuck in a one size fits all treatment for a long time," said Dr. Murrough. "A new class of medicines could give us an opportunity to treat patients based on the specific underlying cause of their disease."

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Other Mount Sinai researchers involved in this study include Aaron Tan, PhD candidate; Sara Costi, MD, Research Fellow; Laurel Morris, PhD, Post-Doctoral Fellow; Nicholas Van Dam, PhD, Adjunct Assistant Professor, Psychiatry; Ming-Hu Han, PhD, Associate Professor of Pharmacological Science and Neuroscience; and Eric Nestler, MD, PhD, Director, Friedman Brain Institute.

About Mount Sinai Health System

The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The System includes approximately 6,600 primary and specialty care physicians; 10 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 13 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.

Contact: Rachel Zuckerman
Mount Sinai Press Office
(646) 605-7693
Rachel.Zuckerman@mountsinai.org

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