Comparative study of esketamine and racemic ketamine in treatment-resistant depression
Fernanda S. Correia-Melo, Gustavo C. Leal, Michelle S. Carvalho, Ana Paula Jesus-Nunes, Carolina B.N. Ferreira, Flávia Vieira, Guilherme Magnavita, Lucas A.S. Vale, Rodrigo P. Mello, Carolina Nakahira, Felipe C. Argolo, Tanise Cardoso, Cezar D.S. Souza, Ana Teresa C. Fontes, Marcelo B. Ferreira, Lucas Araújo-de-freitas, Marco A. Tuena, Mariana V.F. Echegaray, Diogo E. Cavalcanti, Ana C. Lucchese, Igor D. Bandeira, Manuela Telles, Cássio S. Lima, Aline S. Sampaio, Samantha S. Silva, Roberta F. Marback, José A. Del-Porto, José Neander Abreu, Luciana M. Sarin, Camilla S. Paixão, Lucas P. Carvalho, Paulo R.L. Machado, Gustavo Turecki, Acioly L.T. Lacerda, Lucas C. Quarantini
Medicine September 1, 2018 DOI: 10.1097/md.0000000000012414 via OpenAlex
Summary
AI-generated from the abstractA protocol describes a planned randomized, controlled, double-blind noninferiority trial comparing a single infusion of esketamine (0.25 mg/kg) with racemic ketamine (0.5 mg/kg) for treatment-resistant depression. The primary outcome is remission rates at 24 and 72 hours after infusion. Secondary outcomes include cognition, dissociation, and blood biomarkers. The authors state that no study has directly compared these two forms, and a head-to-head test is needed to see if esketamine is comparable in efficacy and safety.
Study at a glance
| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Population | Adults 18 years or older with treatment-resistant major depression |
| Interventions | Esketamine Ketamine |
| Dose | 0.25 mg/kg esketamine, 0.5 mg/kg ketamine |
| Duration | Single 40-minute infusion, with assessments at 24 and 72 hours |
| Citations | 61 |
| Key finding | The protocol outlines a noninferiority trial to determine whether esketamine is comparable to racemic ketamine for treatment-resistant depression. |
Abstract
INTRODUCTION: The use of ketamine as an option in the treatment of depressive disorder is growing rapidly, supported by numerous clinical trials attesting its efficacy and safety. Esketamine, the S (+) enantiomer of ketamine, is the most widely used form in the anesthetic environment in some countries, and new studies have shown that it may also be effective in depression and with better tolerability. However, no study so far has directly compared esketamine with racemic ketamine. Here we propose a protocol of a clinical trial to evaluate esketamine as a noninferior medication when compared to ketamine in the treatment of patients with treatment-resistant depression. METHODS/DESIGN: This study protocol is for a randomized, controlled, double-blind noninferiority clinical trial. Subjects will be 18 years or older, with major depression characterized as treatment-resistant. Participants will receive a single infusion of either esketamine (0.25 mg/kg) or ketamine (0.5 mg/kg) over 40 minutes. The primary outcome will be the difference in remission rates between the 2 treatment arms at 24 and 72 hours after drug infusion. Secondary outcomes will include other timepoints, measurements of cognition, dissociation, and blood biomarkers. DISCUSSION: A head-to-head study is the best way to evaluate whether the esketamine is in fact comparable to the racemic ketamine in terms of both efficacy and safety, and, if positive, it would be an initial step to increase the access to that type of treatment worldwide. ETHICS AND DISSEMINATION: The study was approved by the local Institutional Review Board (University Hospital Professor Edgard Santos-Federal University of Bahia-Number: 46657415.0.0000.0049). Subjects will only participate after voluntarily agreeing and signing the Informed Consent Form. The study findings will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION: This trial has been registered in the Japan Primary Registries Network (JPRN): UMIN000032355, which is affiliated with the World Health Organization.