@article{7e1dbb4419c0452f833540c07503c79c,
title = "A randomized controlled trial of intranasal ketamine in major depressive disorder",
abstract = "Background The N-methyl-D-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability, and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial.Methods In a randomized, double-blind, crossover study, 20 patients with major depression were randomly assigned, and 18 completed 2 treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution. The primary efficacy outcome measure was change in depression severity 24 hours after ketamine or placebo, measured using the Montgomery-{\AA}sberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured.Results Patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo (t = 4.39, p <.001; estimated mean Montgomery-{\AA}sberg Depression Rating Scale score difference of 7.6 ± 3.7; 95% confidence interval, 3.9-11.3). Response criteria were met by 8 of 18 patients (44%) 24 hours after ketamine administration compared with 1 of 18 (6%) after placebo (p =.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters.Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.",
keywords = "Antidepressant, depression, glutamate, intranasal, ketamine, treatment resistant",
author = "Lapidus, {Kyle A.B.} and Levitch, {Cara F.} and Perez, {Andrew M.} and Brallier, {Jess W.} and Parides, {Michael K.} and Laili Soleimani and Adriana Feder and Iosifescu, {Dan V.} and Charney, {Dennis S.} and Murrough, {James W.}",
note = "Funding Information: This work was supported by National Institutes of Health Grant Nos. UL1TR000067 (Mount Sinai Clinical and Translational Science Award) and K23MH094707 (JWM) and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award from the Brain and Behavior Research Foundation (KABL). A portion of the data from the current study was previously presented at the 52nd annual meeting of the American College of Neuropsychopharmacology. Funding Information: The content of this article is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health or other sponsoring entity. In the past 2 years, JWM has received research support from the National Institutes of Health, the National Institute of Mental Health, the Department of Veterans Affairs, the Doris Duke Charitable Foundation, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, Janssen Research and Development, and Avanir Pharmaceuticals; he has served on advisory boards for Janssen Research and Development and Genentech and has provided consultation services for ProPhase, LLC, and Impel NeuroPharma. KABL has received research support from the Brain and Behavior Research Foundation, American Psychiatric Institute for Research and Education Janssen Resident Psychiatric Research Scholars, and the Le Foundation; he has received consulting fees from LCN Consulting and serves on the advisory board for Halo Neuro Inc. DVI has received research funding through Icahn School of Medicine at Mount Sinai from AstraZeneca, Brainsway, Euthymics Bioscience, NeoSync, Roche, and Shire; he has received consulting fees for Avanir Pharmaceuticals, CNS Response, Otsuka Pharmaceutical Co, Ltd, Servier Laboratories, and Sunovion Pharmaceuticals, Inc. DSC has received consulting fees or research support from the United States Department of Defense, National Institutes of Health, National Institute of Mental Health, National Alliance for Research on Schizophrenia and Depression , United States Army Medical Research Acquisition Activity, and CNS Spectrums; he a member of the Advisory and Editorial Boards of the Institute of Medicine Committee on Department of Homeland Security Workforce Resilience. DSC (Dean of Icahn School of Medicine at Mount Sinai and coinvestigator 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. DSC and Icahn School of Medicine at Mount Sinai could potentially benefit from the results of this study. DSC and AF (a coinvestigator on this study) are named coinventors on a use patent application filed by Mount Sinai for the use of ketamine as a treatment for posttraumatic stress disorder. If ketamine were shown to be effective in the treatment of posttraumatic stress disorder and received approval from the U.S. Food and Drug Administration for this indication, DSC, AF, and the Icahn School of Medicine at Mount Sinai could benefit financially. All other authors report no biomedical financial interests or potential conflicts of interest. ",
year = "2014",
month = dec,
day = "15",
doi = "10.1016/j.biopsych.2014.03.026",
language = "English (US)",
volume = "76",
pages = "970--976",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "12",
}