Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study.
F. S. Correia-Melo, G. C. Leal, F. Vieira, A. P. Jesus-Nunes, R. Mello, G. Magnavita, A. T. Caliman-Fontes, Mariana V F Echegaray, I. D. Bandeira, Samantha S. Silva, Diogo E. Cavalcanti, Lucas Araújo-de-freitas, L. Sarin, M. A. Tuena, C. Nakahira, A. Sampaio, J. A. Del-Porto, G. Turecki, C. Loo, A. Lacerda, L. Quarantini
Journal of Affective Disorders November 14, 2019 DOI: 10.1016/j.jad.2019.11.086 via Semantic Scholar
Summary
In adults with treatment-resistant depression, a single intravenous infusion of esketamine (0.25 mg/kg) was non-inferior to ketamine (0.5 mg/kg) for achieving remission 24 hours later. Among 63 participants, 29.4% in the esketamine group and 24.1% in the ketamine group showed remission, a difference of 5.3% that fell within the predefined non-inferiority margin. Depression scores on the Montgomery-Åsberg Depression Rating Scale improved similarly in both groups, and side effects were mild and comparable. The findings suggest that esketamine at half the dose of ketamine offers equivalent short-term efficacy and safety.
Study at a glance
| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 63 |
| Population | Patients with treatment-resistant depression |
| Keywords | Medicine |
| Citations | 188 |
| Key finding | 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.