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Intravenous arketamine for treatment-resistant depression: open-label pilot study

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Abstract

We aimed to analyze the efficacy and safety of arketamine, the R(−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean difference of 20.3 points [CI 95% 13.6–27.0; p < 0.001]; dissociation was nearly absent. Arketamine might produce fast-onset and sustained antidepressant effects in humans with favorable safety profile, like previously reported with animals; further controlled-trials are needed.

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Acknowledgments

This work was supported by the Programa de Pesquisa para o SUS (PPSUS/BA research grant number 003/2017), a public research-funding program, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Finance Code 001. The authors would like to thank Rodrigo L. Alves, Jessica P. Matos and Maria São Pedro for their technical assistance.

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Authors and Affiliations

  1. Hospital Universitário Professor Edgard Santos, Serviço de Psiquiatria, Universidade Federal da Bahia, 3º andar, Rua Dr. Augusto Viana S/N, Salvador, Bahia, 40110-060, Brazil

    Gustavo C. Leal & Lucas C. Quarantini

  2. Laboratório de Neuropsicofarmacologia, Universidade Federal da Bahia, Salvador, Bahia, Brazil

    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 & Lucas C. Quarantini

  3. Programa de Pós-Graduação Em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil

    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, Aline S. Sampaio & Lucas C. Quarantini

  4. Laboratório de Pesquisa Em Neuropsicologia Clínica e Cognitiva, Universidade Federal da Bahia, Salvador, Bahia, Brazil

    Cassio S. Lima, Breno L. S. Marques & Marília L. O. Bezerra

  5. Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Bahia, Brazil

    Aline S. Sampaio & Lucas C. Quarantini

  6. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Gerard Sanacora

  7. McGill Group for Suicide Studies, Department of Psychiatry, Douglas Mental Health University Institute and McGill University, Montreal, Canada

    Gustavo Turecki

  8. School of Psychiatry, University of New South Wales and Black Dog Institute, Sydney, NSW, Australia

    Colleen Loo

  9. Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil

    Acioly L. T. Lacerda

  10. Instituto Sinapse de Neurociências Clínicas, Campinas, São Paulo, Brazil

    Acioly L. T. Lacerda

Authors
  1. Gustavo C. Leal
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  2. Igor D. Bandeira
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  3. Fernanda S. Correia-Melo
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  4. Manuela Telles
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  5. Rodrigo P. Mello
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  6. Flavia Vieira
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  7. Cassio S. Lima
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  8. Ana Paula Jesus-Nunes
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  9. Lívia N. F. Guerreiro-Costa
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  10. Roberta F. Marback
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  11. Ana Teresa Caliman-Fontes
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  12. Breno L. S. Marques
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  13. Marília L. O. Bezerra
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  14. Alberto L. Dias-Neto
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  15. Samantha S. Silva
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  16. Aline S. Sampaio
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  17. Gerard Sanacora
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  18. Gustavo Turecki
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  19. Colleen Loo
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  20. Acioly L. T. Lacerda
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  21. Lucas C. Quarantini
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Corresponding author

Correspondence to Lucas C. Quarantini.

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Conflict of interest

Dr. Quarantini reports consulting fees from Allergan, Abbot, Janssen Pharmaceutical and Lundbeck and research fees from Janssen Pharmaceutical. Dr. Lacerda reports grants and personal fees from Janssen Pharmaceutical, personal fees from Daiichi Sankyo, Cristalia Produtos Químicos e Farmacêuticos, Libbs, Pfizer, Myralis Farma, Aché Laboratórios, Hypera Pharma and Sanofi-Aventis, grants from Eli Lilly, H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, Forum Pharmaceuticals and from public programs: CNPq and FAPESP. Dr. Sanacora has received consulting fees from Allergan, Alkermes, AstraZeneca, Avanier, Axsome Therapeutics, Pharmaceuticals, Biohaven Pharmaceuticals, Bristol-Myers Squibb, Clexio Biosciences, Epiodyne, Intra-Cellular Therapies, Janssen, Merck & Co., Naurex, Navitor, NeruoRx, Novartis, Noven Pharmaceuticals, Otsuka, Perception Neuroscience, Praxis Therapeutics, Sage Pharmaceuticals, Servier Pharmaceuticals, Taisho Pharmaceuticals, Teva, Valeant, and Vistagen therapeutics over the last 24 months. He has also received additional research contracts from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Hoffman La-Roche, Merck, Naurex, and Servier over the last 24 months. Free medication was provided to GS for an NIH-sponsored study by Sanofi-Aventis. In addition Dr. Sanacora holds equity in BioHaven Pharmaceuticals and is a co-inventor on a US patent (#8,778,979) held by Yale University and is a co-inventor on U.S. Provisional Patent Application No. 047162-7177P1 (00754) filed on August 20, 2018 by Yale University Office of Cooperative Research OCR 7451 US01 Abdallah, C, Krystal, JH, Duman, R, Sanacora, G. Combination Therapy for Treating or Preventing Depression or Other Mood Diseases.Yale University, Dr. Sanacora’s employer, has a financial relationship with Janssen Pharmaceuticals, and may in the future receive financial benefits from this relationship. The University has put multiple measures in place to mitigate this institutional conflict of interest. Questions about the details of these measures should be directed to Yale University’s Conflict of Interest office. The other authors report no conflicts of interest.

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Leal, G.C., Bandeira, I.D., Correia-Melo, F.S. et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci 271, 577–582 (2021). https://doi.org/10.1007/s00406-020-01110-5

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