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

Jaskaran Singh, Maggie Fedgchin, Ella Daly, Liwen Xi, Caroline Melman, Geert De Bruecker, Andre Tadic, Pascal Sienaert, Frank Wiegand, Husseini Manji, Wayne C. Drevets, Luc Van Nueten

Biological Psychiatry November 4, 2015 DOI: 10.1016/j.biopsych.2015.10.018 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 30
Population Patients with treatment-resistant depression
Intervention Esketamine
Dose 0.20 mg/kg or 0.40 mg/kg
Duration 40-minute infusion on day 1, with assessment on day 2
Topics Depression Esketamine
Citations 466
Key findings Both 0.20 mg/kg and 0.40 mg/kg doses of intravenous esketamine produced rapid and significant antidepressant effects compared to placebo in treatment-resistant depression, with the lower dose potentially offering better tolerability.

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.

In the evidence

This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: Esketamine for depression Supports

    Both 0.20 and 0.40 mg/kg IV esketamine produced rapid, significant MADRS improvement versus placebo by day 2, with dose-dependent adverse events.

    Synthesized

  • State of the evidence: Ketamine for depression Supports

    Both 0.20 and 0.40 mg/kg IV esketamine produced rapid, significant MADRS improvement versus placebo by day 2.

    Synthesized

  • State of the evidence: Esketamine Supports

    Both 0.20 mg/kg and 0.40 mg/kg intravenous esketamine produced rapid and significant antidepressant effects compared with placebo.

    Synthesized

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

Citations in the library

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