Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis
Open accessAbstract
Background Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear.Objectives This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.Design Systematic review and meta-analysis.Data sources We searched PubMed, MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for relevant studies published since database inception and December 17, 2019.Study eligibility criteria We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression.Outcomes Primary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events.Analysis Evidence from randomized controlled trials was synthesized as rate ratios (RRs) for treatment response, disorder remission, adverse events, and withdrawals and as standardized mean differences (SMDs) for change in symptoms, via random-effects meta-analyses.Findings 24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37).Conclusions Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.
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One meta-analysis found that racemic ketamine produced a greater overall antidepressant response and fewer dropouts than esketamine.
“One meta-analysis found that racemic ketamine elicited a greater overall antidepressant response and had fewer dropouts across studies than esketamine [36].”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [36]
A recent meta-analysis has indicated significantly greater response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37), favoring intravenous ketamine over intranasal esketamine.
“Notably, a recent meta-analysis has indicated significantly greater response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37), favoring intravenous ketamine over intranasal esketamine [118].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [118]
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- Authors
- Bahji, A., Vazquez, G. H., & Zarate, C. A.
- Affiliations
- Queen's University (CA)
- National Institutes of Health (US)
- Corresponding author
- Zarate, Carlos A.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 278
- Pages
- 542-555
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC7704936
- OpenAlex
- W3088001093
- Cited by
- 408
- References
- 115
- Citations by year
- 2026: 46 · 2025: 76 · 2024: 87 · 2023: 85 · 2022: 79 · 2021: 31 · 2020: 3
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Update notices
- erratum (2021-02-15)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- ketamine, esketamine, racemic ketamine, major depressive disorder, bipolar depression, treatment response, remission, treatment discontinuation, adverse events, suicidality, intravenous administration, intranasal administration, drug efficacy comparison
- MeSH terms
- Antidepressive Agents, Depression, Depressive Disorder, Major, Major Depressive Disorder, Humans, Ketamine
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