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)
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.
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Esketamine 0.25 mg/kg was non-inferior to ketamine 0.5 mg/kg for remission 24 hours after a single intravenous infusion, with similar mild side effects.
Synthesized
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State of the evidence: Esketamine Supports
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.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.