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-Åsberg 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-Åsberg 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.
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Kyle A B
authors.initials: KA
authors.lastname: Lapidus
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Cara F
authors.initials: CF
authors.lastname: Levitch
authors.affiliation: Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Perez
authors.affiliation: Department of Anesthesiology, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Jess W
authors.initials: JW
authors.lastname: Brallier
authors.affiliation: Department of Health Evidence and Policy, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parides
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; James J. Peters Veterans Affairs Medical Center, Bronx, New York.
authors.forename: Laili
authors.initials: L
authors.lastname: Soleimani
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Feder
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Dan V
authors.initials: DV
authors.lastname: Iosifescu
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.affiliation: Mood and Anxiety Disorders Program, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York. Electronic address: james.murrough@mssm.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000097:blood; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine; C033419:norketamine
keywords: Antidepressant; depression; glutamate; intranasal; ketamine; treatment resistant