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Biol Psychiatry. 2016 Sep 15;80(6):424-31. doi: 10.1016/j.biopsych.2015.10.018. Epub 2015 Nov 3.

Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study.

Author information

1
Janssen Research & Development, LLC, San Diego, California. Electronic address: jsingh25@its.jnj.com.
2
Janssen Research & Development, LLC, San Diego, California.
3
Janssen-Cilag B.V., Tilburg, Netherlands.
4
Psychiatric Hospital Zoete Nood Gods, Lede, Belgium.
5
Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany.
6
Department of Mood Disorders, University Psychiatric Centre, Katholieke Universiteit Leuven (University of Leuven), Leuven.
7
Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Efficacy; Esketamine; Intravenous; Safety; TRD; Treatment-resistant depression

PMID:
26707087
DOI:
10.1016/j.biopsych.2015.10.018
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