Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses
This review (2021) summarizes the current state of research regarding the use of ketamine and esketamine for depression. Across 11 studies it was found that ketamine alleviated symptoms of depression 40 min to 1 week while esketamine improved symptoms at 2 hours to 4 weeks. The methodological quality of most reviews was described as critically low.
Authors
- de Mendoça Lima, T.
- Visacri, M. B.
- Aguiar, P. M.
Published
Abstract
Purpose
To summarize the evidence of efficacy and safety of the use of ketamine and esketamine for depression.
Methods
A literature search was performed in Medline, the Cochrane Library, LILACS, and CRD until November 2020. We included systematic reviews with meta-analyses of randomized controlled trials on the use of ketamine and esketamine in adult patients with depression. Two authors independently performed the study selection and data extraction. The AMSTAR-2 tool was used to appraise the quality of included reviews.
Results
A total of 118 records were identified, and 11 studies fully met the eligibility criteria. Compared to control, ketamine improved the clinical response at 40 min to 1 week and clinical remission at 80 min to 72 h, and esketamine improved both outcomes at 2 h to 4 weeks. Ketamine and esketamine also had a beneficial effect on the depression scales score and suicidality. For adverse events, oral ketamine did not show significant change compared to control, while intranasal esketamine showed difference for any events, such as dissociation, dizziness, hypoesthesia, and vertigo. Most reviews were classified as critically low quality, and none of them declared the source of funding of the primary studies and assessed the potential impact of risk of bias in primary studies.
Conclusion
Ketamine and esketamine showed a significant antidepressant action within a few hours or days after administration; however, the long-term efficacy and safety are lacking. In addition, the methodological quality of the reviews was usually critically low, which may indicate the need for higher quality evidence in relation to the theme.
Research Summary of 'Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses'
Introduction
Depression is a prevalent, disabling psychiatric disorder characterised by persistent low mood, anhedonia, cognitive and somatic symptoms, and sometimes suicidal ideation. Standard antidepressant treatments and electroconvulsive therapy can be effective but typically require days to weeks to achieve response, and many patients experience suboptimal outcomes. Early studies identified modulation of the glutamatergic system—specifically NMDA receptor antagonism—as a potential rapid-acting mechanism; subsequent work has shown that subanaesthetic doses of ketamine (a racemic mixture) and esketamine (S-ketamine) can produce rapid antidepressant effects and may also involve opioid-system activation. Intranasal esketamine has regulatory approval in some jurisdictions, but off‑label and clinical use of these agents has expanded despite remaining uncertainties over longer-term efficacy and safety. This overview sought to summarise the available evidence from systematic reviews with pairwise meta-analyses concerning the efficacy and safety of ketamine and esketamine for depression in adults. In addition to aggregating reported effect estimates, the investigators examined the methodological quality of included reviews to inform the reliability of the synthesized evidence and identify gaps for future research.
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 Typemeta
- Journal
- Compounds
- Topics
- APA Citation
Lima, T. D. M., Visacri, M. B., & Aguiar, P. M. (2022). Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. European Journal of Clinical Pharmacology, 78(3), 311-338. https://doi.org/10.1007/s00228-021-03216-8
References (13)
Papers cited by this study that are also in Blossom
Newport, D. J., Carpenter, L. L., Mcdonald, W. M. et al. · American Journal of Psychiatry (2015)
Nuñez, N. A., Joseph, B., Pahwa, M. et al. · Psychopharmacology Bulletin (2025)
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Short, B., Fong, J., Galvez, V. et al. · Lancet Psychiatry (2017)
Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)
Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)
Jafarinia, M., Afarideh, M., Tafakhori, A. et al. · Journal of Affective Disorders (2016)
Grunebaum, M. F., Ellis, S. P., Keilp, J. G. et al. · Bipolar Disorders (2017)
Show all 13 referencesShow fewer
Su, T. P., Chen, M. H., Li, C. T. et al. · Neuropsychopharmacology (2017)
Grunebaum, M. F., Galfalvy, H. C., Choo, T. H. et al. · American Journal of Psychiatry (2018)
Ionescu, D. F., Bentley, K. H., Eikermann, M. et al. · Journal of Affective Disorders (2019)
Cited By (2)
Papers in Blossom that reference this study
Rodgers, A., Bahceci, D., Davey, C. G. et al. · Australian and new-zealand Journal of Psychiatry (2023)
Shamabadi, A., Ahmadzade, A., Hasanzadeh, A. · British Journal of Clinical Pharmacology (2022)
Your Personal Research Library
Go Pro to save papers, add notes, rate studies, and organize your research into custom shelves.