Fernanda S Correia-Melo1, Gustavo C Leal2, Flávia Vieira3, Ana Paula Jesus-Nunes3, Rodrigo P Mello3, Guilherme Magnavita4, Ana Teresa Caliman-Fontes4, Mariana V F Echegaray4, Igor D Bandeira3, Samantha S Silva4, Diogo E Cavalcanti5, Lucas Araújo-de-Freitas3, Luciana M Sarin6, Marco A Tuena6, Carolina Nakahira6, Aline S Sampaio7, José A Del-Porto6, Gustavo Turecki8, Colleen Loo9, Acioly L T Lacerda10, Lucas C Quarantini11. 1. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil; Postgraduate Program in Medicine and Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil. Electronic address: lcq@ufba.br. 2. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil; Postgraduate Program in Medicine and Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil; Division of Psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil. 3. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil; Postgraduate Program in Medicine and Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil. 4. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil. 5. Division of Psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil. 6. Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil. 7. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil; Department of Neuroscience and Mental Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil. 8. McGill Group for Suicide Studies, Douglas Mental Health University Institute & Department of Psychiatry, McGill University, Montreal, Canada. 9. School of Psychiatry, University of New South Wales, Sydney, Australia; Black Dog Institute, Sydney, Australia; St George Hospital, South Eastern Sydney Health, Sydney, Australia. 10. Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil; Interdisciplinary Laboratory of Clinical Neurosciences, Federal University of São Paulo, São Paulo, Brazil; Sinapse Institute of Clinical Neurosciences, Campinas, Brazil. 11. Laboratory of Neuropsychopharmacology, Federal University of Bahia, Salvador, Brazil; Postgraduate Program in Medicine and Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil; Division of Psychiatry, Professor Edgard Santos University Hospital, Federal University of Bahia, Salvador, Brazil; Department of Neuroscience and Mental Health, Medical School of Bahia, Federal University of Bahia, Salvador, Brazil.
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.
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.
Authors: Gustavo C Leal; Igor D Bandeira; Fernanda S Correia-Melo; Manuela Telles; Rodrigo P Mello; Flavia Vieira; Cassio S Lima; Ana Paula Jesus-Nunes; Lívia N F Guerreiro-Costa; Roberta F Marback; Ana Teresa Caliman-Fontes; Breno L S Marques; Marília L O Bezerra; Alberto L Dias-Neto; Samantha S Silva; Aline S Sampaio; Gerard Sanacora; Gustavo Turecki; Colleen Loo; Acioly L T Lacerda; Lucas C Quarantini Journal: Eur Arch Psychiatry Clin Neurosci Date: 2020-02-20 Impact factor: 5.270
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