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Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study.

Fernanda S. Correia-Melo, Gustavo C. Leal, Flávia Vieira, A. P. Jesus-Nunes, Rodrigo P Mello, Guilherme M. Magnavita, A. T. Caliman-Fontes, Mariana V F Echegaray, Igor D. Bandeira, Samantha S. Silva, Diogo E. Cavalcanti, Lucas Araújo-de-freitas, Luciana M. Sarin, Marco A. Tuena, Carolina Nakahira, A. Sampaio, José A. Del-Porto, Gustavo Turecki, Colleen Loo, Acioly L T Lacerda, Lucas C Quarantini

Journal of Affective Disorders November 14, 2019 DOI: 10.1016/j.jad.2019.11.086 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 63
Population Patients with treatment-resistant depression
Interventions Ketamine Esketamine
Dose 0.5 mg/kg ketamine or 0.25 mg/kg esketamine
Duration Single 40-minute infusion, 24-hour follow-up
Topics Depression Esketamine Ketamine
Citations 188
Key findings Esketamine 0.25 mg/kg was non-inferior to ketamine 0.5 mg/kg for remission of treatment-resistant depression 24 hours after a single intravenous infusion.

Abstract

Background: Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD).

Methods: This is a randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Åsberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%.

Results: 63 subjects were included and randomly assigned (29 to receive ketamine and 34 to receive esketamine). At 24 h, 24.1% of participants in the ketamine group and 29.4% of participants in the esketamine group showed remission, with a difference of 5.3% (95% CILB -13.6%), confirming non-inferiority. MADRS scores improved from 33 (SD 9.3) to 16.2 (SD 10.7) in the ketamine group and from 33 (SD 5.3) to 17.5 (SD 12.2) in the esketamine one, with a difference of -5.27% (95% CILB, -13.6). Both groups presented similar mild side effects.

Conclusions: Esketamine was non-inferior to ketamine for TRD 24 h following infusion. Both treatments were effective, safe, and well tolerated.

Trial Registration: Registered in Japan Primary Registries Network: UMIN000032355.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: Esketamine for depression Supports

    Esketamine 0.25 mg/kg was non-inferior to ketamine 0.5 mg/kg for 24-hour remission, with similar mild side effects.

    Synthesized

  • State of the evidence: Esketamine Supports

    Esketamine 0.25 mg/kg was non-inferior to ketamine 0.5 mg/kg for remission 24 hours after a single intravenous infusion.

    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

Cited by 96

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Related reading

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Depression Esketamine Ketamine

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