title: A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression.
abstract: OBJECTIVE
  Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.
  
  
  METHODS
  In a multicenter, double-blind study, adults (ages 18-64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).
  
  
  RESULTS
  In total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was -18.4 (SD=12.0) for ketamine and -5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was -17.7 (SD=7.3) for ketamine and -3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, -12.2 [SD=12.8] on day 4; thrice-weekly, -14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing.
  
  
  CONCLUSIONS
  Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Jaskaran B
authors.initials: JB
authors.lastname: Singh
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Maggie
authors.initials: M
authors.lastname: Fedgchin
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Ella J
authors.initials: EJ
authors.lastname: Daly
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Peter
authors.initials: P
authors.lastname: De Boer
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Cooper
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Pilar
authors.initials: P
authors.lastname: Lim
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Christine
authors.initials: C
authors.lastname: Pinter
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: James W
authors.initials: JW
authors.lastname: Murrough
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Benji
authors.initials: B
authors.lastname: Kurian
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Andrew
authors.initials: A
authors.lastname: Winokur
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Husseini
authors.initials: H
authors.lastname: Manji
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: From Janssen Research and Development, Titusville, N.J., and Beerse, Belgium; the Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, N.Y.; the Department of Psychiatry, Yale University, New Haven, Conn.; the Department of Psychiatry and Behavioral Neurobiology, School of Medicine, University of Alabama at Birmingham; the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas; the Institute of Living, Hartford, Conn.; University of Connecticut Health Center, Farmington; the Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Nueten
mesh_terms: D000293:Adolescent; D000328:Adult; D061218:Depressive Disorder, Treatment-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000627:therapeutic use*; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D055815:Young Adult
chemical_list: D007649:Ketamine