title: Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study.
abstract: The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD).
  
  
  
  This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .20 mg/kg or .40 mg/kg esketamine or placebo over 40 minutes on day 1. The primary end point was change in Montgomery-Åsberg Depression Rating Scale total score from day 1 (baseline) to day 2. Nonresponders who received placebo on day 1 were randomly assigned again 1:1 to IV esketamine .20 mg/kg or .40 mg/kg on day 4. Secondary efficacy and safety measures were also evaluated.
  
  
  
  Of the enrolled patients, 97% (29 of 30) completed the study. The least squares mean changes (SE) from baseline to day 2 in Montgomery-Åsberg Depression Rating Scale total score for the esketamine .20 mg/kg and .40 mg/kg dose groups were -16.8 (3.00) and -16.9 (2.61), respectively, and showed significant improvement (one-sided p = .001 for both groups) compared with placebo (-3.8 [2.97]). Esketamine showed a rapid (within 2 hours) and robust antidepressant effect. Treatment-emergent adverse events were dose dependent. The most common treatment-emergent adverse events were headache, nausea, and dissociation; the last-mentioned was transient and did not persist beyond 4 hours from the start of the esketamine infusion.
  
  
  
  A rapid onset of robust antidepressant effects was observed in patients with TRD after a 40-minute IV infusion of either .20 mg/kg or .40 mg/kg of esketamine. The lower dose may allow for better tolerability while maintaining efficacy.
authors.affiliation: Janssen Research & Development, LLC, San Diego, California. Electronic address: jsingh25@its.jnj.com.
authors.forename: Jaskaran B
authors.initials: JB
authors.lastname: Singh
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Maggie
authors.initials: M
authors.lastname: Fedgchin
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Ella
authors.initials: E
authors.lastname: Daly
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Liwen
authors.initials: L
authors.lastname: Xi
authors.affiliation: Janssen-Cilag B.V., Tilburg, Netherlands.
authors.forename: Caroline
authors.initials: C
authors.lastname: Melman
authors.affiliation: Psychiatric Hospital Zoete Nood Gods, Lede, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: De Bruecker
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Tadic
authors.affiliation: Department of Mood Disorders, University Psychiatric Centre, Katholieke Universiteit Leuven (University of Leuven), Leuven.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sienaert
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Frank
authors.initials: F
authors.lastname: Wiegand
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Husseini
authors.initials: H
authors.lastname: Manji
authors.affiliation: Janssen Research & Development, LLC, San Diego, California.
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Van Nueten
mesh_terms: D000293:Adolescent; D000328:Adult; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007649:Ketamine
keywords: Efficacy; Esketamine; Intravenous; Safety; TRD; Treatment-resistant depression