Intranasal Ketamine Confers Rapid Antidepressant Effect in Depression
Mount Sinai team cautiously optimistic that door could swing open to a new antidepressant drug class.
A research team from the Icahn School of Medicine at Mount Sinai published the first controlled evidence showing that an intranasal ketamine spray conferred an unusually rapid antidepressant effect –within 24 hours—and was well tolerated in patients with treatment-resistant major depressive disorder. This is the first study to show benefits with an intranasal formulation of ketamine. Results from the study were published online in the peer-reviewed journal Biological Psychiatry on April 2, 2014.
Of 18 patients completing two treatment days with ketamine or saline, eight met response criteria to ketamine within 24 hours versus one on saline. Ketamine proved safe with minimal dissociative effects or changes in hemodynamic dimensions.
The study randomized 20 patients with major depressive disorder to ketamine (a single 50 mg dose) or saline in a double-blind, crossover study. Change in depression severity was measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included the durability of response, changes in self-reports of depression, anxiety, and the proportion of responders.
"One of the primary effects of ketamine in the brain is to block the NMDA [N-methyl-d-aspartate] glutamate receptor," said James W. Murrough, MD, principal investigator of the study, and Assistant Professor of Psychiatry and Neuroscience, and Associate Director of the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai. "There is an urgent clinical need for new treatments for depression with novel mechanisms of action. With further research and development, this could lay the groundwork for using NMDA targeted treatments for major depressive disorder."
"We found intranasal ketamine to be well tolerated with few side effects," said Kyle Lapidus, MD, PhD, Assistant Professor of Psychiatry, at the Icahn School of Medicine at Mount Sinai.
One of the most common NMDA receptor antagonists, ketamine is an FDA-approved anesthetic. It has been used in animals and humans for years. Ketamine has also been a drug of abuse and can lead to untoward psychiatric or cognitive problems when misused. In low doses, ketamine shows promise in providing rapid relief of depression, with tolerable side effects.
Study co-author Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and President for Academic Affairs for the Mount Sinai Health System, and a world expert on the neurobiology and treatment of mood disorders, said: "What we have here is a proof of concept study and we consider the results very promising. We hope to see this line of research further developed so that we have more treatments to offer patients with severe, difficult-to-treat major depressive disorder."
Going forward, the Mount Sinai research team hopes to examine the mechanism of action, dose ranging, and use functional brain imaging to further elucidate how ketamine works.
Kyle A. Lapidus, MD, PhD, was the lead author of the study. All other contributors to the study were from the Icahn School of Medicine at Mount Sinai: Cara Levitch; Andrew M. Perez, MD; Jess Brallier, MD; Michael K. Parides, PhD; Laili Soleimani, MD; Adriana Feder, MD; and Dan Iosifescu, MD.
Dr. Charney (Dean of Icahn School of Medicine at Mount Sinai and co-investigator on this study), and Icahn School of Medicine at Mount Sinai have been named on a use patent on Ketamine for the treatment of depression. The Icahn School of Medicine has entered into a licensing agreement for the use of ketamine as therapy for treatment-resistant depression. Dr. Charney and Icahn School of Medicine at Mount Sinai could potentially benefit from the results of this study.
This study was supported by Grant number UL1TR000067 from the National Institutes of Health.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12-minority-owned free-standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.