Intravenous arketamine for treatment-resistant depression: open-label pilot study
This open-label study (n=7) study investigated the antidepressant efficacy of (R-)ketamine (35mg/70kg), which has been implicated by animal studies to be more potent and longer-lasting compared to (S-)ketamine. Results demonstrate (R-)ketamine's ability to produce a fast and robust antidepressant effect in patients with depression, with potentially greater and longer-lasting effects, greater response rate, and a lower remission rate than effects reported for (S-)ketamine, although this study had a small sample size and lacked placebo-control.
Authors
- Gerard Sanacora
- Colleen Loo
- Kenji Hashimoto
Published
Abstract
Introduction
We aimed to analyze the efcacy and safety of arketamine, the R(−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans.
Methods
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.
Results
Mean MADRS dropped from 30.7 before infusion to 10.4 after one day, a mean diference of 20.3 points [CI 95% 13.6-27.0; p<0.001]; dissociation was nearly absent.
Discussion
Arketamine might produce fast-onset and sustained antidepressant efects in humans with favorable safety profle, like previously reported with animals; further controlled-trials are needed.
Research Summary of 'Intravenous arketamine for treatment-resistant depression: open-label pilot study'
Introduction
Over the past two decades, ketamine and its S(+)-enantiomer esketamine have been shown to produce rapid antidepressant effects in major depressive disorder (MDD), including in patients with treatment-resistant depression (TRD). Wider clinical use has been constrained by concerns about abuse potential, psychotomimetic and cardiovascular side-effects, and relatively short duration of benefit. Preclinical work has suggested that the R(-)-enantiomer of ketamine, arketamine, may produce more potent and longer-lasting antidepressant effects than either racemic ketamine or esketamine and with fewer psychotomimetic effects; limited human data from anaesthetic use and a small healthy volunteer study also suggested a favourable safety profile. Leal and colleagues therefore undertook an exploratory human study to evaluate whether a single intravenous infusion of arketamine produces rapid antidepressant effects in TRD and to characterise its acute safety and dissociative profile. The investigation is presented as a first-in-humans clinical evaluation of arketamine's antidepressant action in this population and intended to inform future controlled trials.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Leal, G. C., Bandeira, I. D., Correia-Melo, F. S., Telles, M., Mello, R. P., Vieira, F., Lima, C. S., Jesus-Nunes, A. P., Guerreiro-Costa, L. N. F., Marback, R. F., Caliman-Fontes, A. T., Marques, B. L. S., Bezerra, M. L. O., Dias-Neto, A. L., Silva, S. S., Sampaio, A. S., Sanacora, G., Turecki, G., Loo, C., . . . Quarantini, L. C. (2021). Intravenous arketamine for treatment-resistant depression: open-label pilot study. European Archives of Psychiatry and Clinical Neuroscience, 271(3), 577-582. https://doi.org/10.1007/s00406-020-01110-5
References (9)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Chen, X., Hou, X., Bai, D. et al. · American Journal of Psychiatry (2019)
Correia-Melo, F. S., Argolo, F. C., Araújo-de-Freitas, L. et al. · Neuropsychiatric Disease And Treatment (2017)
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Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Zhang, J., Hashimoto, K., Li, S. · Pharmacology Biochemistry and Behavior (2014)
Yang, C., Shirayama, Y., Zhang, J-C. et al. · Translational Psychiatry (2020)
Hashimoto, K. · Psychiatry and Clinical Neurosciences (2019)
Han, Y., Chen, J., Zou, D. et al. · Neuropsychiatric Disease And Treatment (2016)
Cited By (8)
Papers in Blossom that reference this study
Veraart, J. K. E., Smith-Apeldoorn, S. Y., van der Meij, A. et al. · Journal of Psychopharmacology (2025)
Dawson, K., May, A., Carangan, J. M. et al. · MedRvix (2024)
Rodgers, A., Bahceci, D., Davey, C. G. et al. · Australian and new-zealand Journal of Psychiatry (2023)
Leal, G. C. · Journal of Affective Disorders (2023)
Zhang, J. C., Yao, W., Hashimoto, K. · Neuropharmacology (2022)
Araújo-de-Freitas, L., Santos-Lima, C., Mendonça-Filho, E. et al. · Psychiatry Research (2021)
Savalia, N., Shao, L-X,, Kwan, A. C. · Trends in Neuroscience (2021)
Hibicke, M., Gobbi, G. · Journal of Neuroscience (2020)
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