Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression
This double-blind, cross-over, placebo-controlled study (n=27) investigated the antidepressant and psychotomimetic effects of a single ketamine infusion (38mg/70kg) in patients diagnosed with major depressive disorder (MDD). Ketamine infusion induced acute psychotomimetic symptoms, which correlated with alleviating negative mood ratings and improving depression symptoms in the days after.
Authors
- Tomáš Páleníček
- Jiří Horacek
Published
Abstract
Objectives
Ketamine and other NMDA (N-methyl-D-aspartate) antagonists produce fast-acting antidepressant-like effects, although the underlying mechanism is unclear. Furthermore, high affinity NMDA antagonists such as ketamine are associated with psychotomimetic effects. To date the link between the antidepressant and psychotomimetic effects of ketamine has not been explored. We examined the relationship between the antidepressant and psychotomimetic effects of a single ketamine infusion in subjects diagnosed with major depressive disorder.
Methods
In a double-blind, cross-over, placebo-controlled, two weeks clinical trial we studied the effects of ketamine (0.54 mg/kg within 30 min) in a group of 27 hospitalized depressive patients.
Results
Higher intensity of psychotomimetic symptoms, measured using BPRS, during ketamine administration correlated with alleviation in mood ratings during the following week with maximum on day seven. Ketamine was superior to placebo in all visits (day 1, 4, and 7) assessed by MADRS with effect size (Cohen´s d) of 0.62, 0.57, and 0.44 respectively. There was no significant correlation between ketamine and nor-ketamine plasma levels and MADRS score change at any study time point.
Conclusion
The substantial relationship between ketamine's antidepressant and psychotomimetic effects was found. This relationship could be mediated by the initial steps of ketamine's action, trough NMDA receptors, shared by both ketamine's clinical effects.
Research Summary of 'Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression'
Introduction
Sos and colleagues situate their work within growing evidence that ketamine, an NMDA (N-methyl-D-aspartate) receptor antagonist, produces rapid antidepressant effects at subanesthetic doses while also causing transient psychotomimetic and dissociative phenomena. Earlier research has established ketamine's rapid mood benefits but left the mechanistic link between those antidepressant effects and the concurrent psychotomimetic effects unclear. The authors note that industry efforts have sought NMDA antagonists that retain antidepressant activity without psychotomimetic effects, but the association between these two domains had not been prospectively explored. This study aimed to evaluate ketamine’s antidepressant efficacy versus placebo in inpatients with major depressive disorder and, a priori, to test whether greater psychotomimetic effects during infusion predict larger subsequent antidepressant responses. The investigators also measured ketamine and nor-ketamine plasma levels to explore whether blood concentrations related to either psychotomimetic or antidepressant effects. The work used a double-blind, placebo-controlled, crossover design to address these questions prospectively in a clinical sample of hospitalised patients with moderate-to-severe depression.
Expert Research Summaries
Go Pro to access AI-powered section-by-section summaries, editorial takes, and the full research toolkit.
Full Text PDF
Full Paper PDF
Create a free account to open full-text PDFs.
Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
(2013). Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression. Neuropsychiatric Disease And Treatment.
References (2)
Papers cited by this study that are also in Blossom
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)
Cited By (47)
Papers in Blossom that reference this study
Tylš, F., Páleníček, T., Klučková, T. et al. · Pharmacological Reports (2025)
Dahan, J. D. C., Dadiomov, D., Bostoen, T. et al. · npj Mental Health Research (2024)
Lii, T. R., Smith, A. E., Flohr, J. R. et al. · Nature Mental Health (2023)
Hartland, H., Mahdavi, K., Jelen, L. A. et al. · Journal of Psychopharmacology (2023)
Price, R., Kissel, N., Baumeister, A. et al. · Molecular Psychiatry (2022)
Medeiros, G. C., Gould, T. D., Prueitt, W. L. et al. · Molecular Psychiatry (2022)
Shamabadi, A., Ahmadzade, A., Hasanzadeh, A. · British Journal of Clinical Pharmacology (2022)
Keeler, J. L., Treasure, J., Juruena, M. F. et al. · Nutrients (2021)
de Mendoça Lima, T., Visacri, M. B., Aguiar, P. M. · European Journal of Clinical Pharmacology (2021)
Cubała, W. J., Szarmach, J., Galuszko-Wegielink, M. et al. · Medicine (2021)
Show all 47 papersShow fewer
Kočárová, C., Horacek, J., Carhart-Harris, R. L. · Frontiers in Psychiatry (2021)
Haarsma, J., Harmer, C. J., Tamm, S. · Brain and Neuroscience Advances (2021)
Sumner, R. L., Chacko, E., Mcmillan, R. et al. · Journal of Psychopharmacology (2021)
Murrough, J. W., Abdallah, C. G., Mathew, S. J. · Nature Reviews Drug Discovery (2021)
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Ortiz, M. I., Gómez-Busto, F. J. · Clinical Neuropsychiatry (2020)
Olson, D. E. · ACS Pharmacology and Translational Science (2020)
Greenway, K. T., Garel, N., Jerome, L. et al. · Expert Review of Clinical Pharmacology (2020)
Mathai, D. S., Meyer, M. J., Storch, E. A. et al. · Journal of Affective Disorders (2020)
Ezquerra-Romano, I. I., Lawn, W., Krupitsky, E. M. et al. · Neuropharmacology (2018)
Wilkinson, S. T., Katz, R. B., Toprak, M. et al. · Journal of Clinical Psychiatry (2018)
Jones, J. L., Mateus, C. F., Malcolm, R. J. et al. · Frontiers in Psychiatry (2018)
Niciu, M. J., Shovestul, B. J., Jaso, B. A. et al. · Journal of Affective Disorders (2018)
Zanos, P., Thompson, S. M., Duman, R. S. et al. · CNS Drugs (2018)
Van Schalkwyk, G. I., Wilkinson, S. T., Davidson, L. et al. · Journal of Affective Disorders (2018)
Carhart-Harris, R. L., Roseman, L., Haijen, E. C. H. M. et al. · Journal of Psychopharmacology (2018)
Roseman, L., Nutt, D. J., Carhart-Harris, R. L. · Frontiers in Pharmacology (2018)
Feifel, D., Malcolm, B., Boggie, D. et al. · Journal of Affective Disorders (2017)
Wilkinson, S. T., Ballard, E. D., Bloch, M. H. et al. · American Journal of Psychiatry (2017)
Short, B., Fong, J., Galvez, V. et al. · Lancet Psychiatry (2017)
Kraus, C., Rabl, U., Vanicek, T. et al. · International Journal of Psychiatry in Clinical Practice (2017)
Dos Santos, R. G., Bouso, J. C., Hallak, J. E. · Journal of Psychedelic Studies (2016)
Zhu, W., Ding, Z., Zhang, Y. et al. · Neuroscience Bulletin (2016)
Han, Y., Chen, J., Zou, D. et al. · Neuropsychiatric Disease And Treatment (2016)
Garcia-Romeu, A., Kersgaard, B., Addy, P. H. · Experimental and Clinical Psychopharmacology (2016)
Bobo, W. V., Vande Voort, J. L., Croarkin, P. E. et al. · Depression and Anxiety (2016)
Kishimoto, T., Chawla, J. M., Hagi, K. et al. · Psychological Medicine (2016)
Schoevers, R. A., Chaves, T. V., Balukova, S. M. et al. · brazilian Journal of Psychiatry (2016)
Romeo, B., Choucha, W., Fossati, P. et al. · Psychiatry Research (2015)
Papakostas, G. I., Ionescu, D. F. · Molecular Psychiatry (2015)
Iadarola, N. D., Niciu, M. J., Richards, E. M. et al. · Therapeutic Advances in Chronic Disease (2015)
Coyle, C. M., Laws, K. R. · Human Psychopharmacology (2015)
Majic, T., Schmidt, T. T., Gallinat, J. · Journal of Clinical Psychopharmacology (2015)
Dutta, A., Mckie, S., Deakin, J. F. W. · Psychiatry Research (2014)
Ari, A., Abdallah, C. G., Sanacora, G. et al. · Annual Review of Medicine (2014)
Fond, G., Loundou, A., Macgregor, A. et al. · Psychopharmacology (2014)
Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F. et al. · Journal of Affective Disorders (2014)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.