The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.
Open accessAbstract
OBJECTIVE: Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. METHOD: This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. CONCLUSIONS: Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
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“A power analysis based on ketamine's antidepressant effects was used to determine the sample size of 18 (Murrough et al, 2013a;Zarate et al, 2006).”
From Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2018) · cites this paper as Murrough et al, 2013a
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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“As an example, we discuss the potential for ketamine-which exhibits both rapid plasticity-enhancing effects in animal models 4,10 and rapid clinical effects in human patients 11,12 -to provide a test of the predictions of this integrative model, including simultaneous and correlated reversals of multiple plasticity-related deficits across levels of analysis.”
From Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model (2020) · cites this paper as [11]
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In the citing paper
“Ketamine, an antagonist of the glutamatergic N-methyl-D-aspartate (NMDA) receptor (an ionotropic glutamate receptor), was shown to exhibit rapid onset and robust, short-term antidepressant effect in patients with treatment-resistant depression (TRD) [1–3].”
From Cardiac Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: Results from the Clinical Development Program (2020) · cites this paper as [3]
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“The lack of efficacy in our trial is likely due the fact that in our study most patients had mild to moderate depression as opposed to the more severe treatment-resistant major depression studied in ketamine clinical trials (Murrough et al, 2013a;Murrough et al, 2013b;Zarate et al, 2006).”
From Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial (2018) · cites this paper as Murrough et al, 2013a
In the citing paper
“Subsequent randomized controlled trials (RCTs) replicated this finding, demonstrating a 60–70% response rate of ketamine in TRD populations.10–14”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [10]
In the citing paper
“However, ketamine’s antidepressant properties are also transient, lasting an average of 1 week following a single infusion10–14 and 18–19 days following repeated infusions.15,16”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [10]
In the citing paper
“Meta-analyses consistently support these findings [91,92,94], establishing ketamine’s AD efficacy in oral and intranasal administration, repeated dosing, an augmenting agent, and patients with treatment-resistant bipolar depression or suicidal ideation [91,94,95,96].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [92]
In the citing paper
“Comparable results have been replicated in several similarly designed RDBPCTs examining single administration of sub-anesthetic dose ketamine in patients with MDD and TRD [73,91,92,93].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [92]
In the citing paper
“Murrough et al., (2013) using a psychoactive placebo, midazolam, demonstrated a 64% response rate for the patients administered ketamine compared to 28% for those who received midazolam 19.”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [19]
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Metadata
- Authors
- Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J.
- Affiliations
- Michael E. DeBakey VA Medical Center (US)
- From the Department of Psychiatry, the Department of Neuroscience, the Department of Anesthesiology, the Department of Pharmacology and Systems Therapeutics, and the Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York; the Department of Anesthesiology and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Michael E. DeBakey VA Medical Center, Houston; and the Center for Clinical Research and Evidence-Based Medicine, University...
- Venue
- American Journal of Psychiatry
- Published
- 2013-10
- Volume
- 170
- Issue
- 10
- Pages
- 1134-1142
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC3992936
- OpenAlex
- W2128918664
- Semantic Scholar
- e34f931c9acf4eb7089a7a613a81eed1d3cfa069
- Cited by
- 1,205
- References
- 39
- Citations by year
- 2026: 48 · 2025: 71 · 2024: 87 · 2023: 92 · 2022: 115 · 2021: 115 · 2020: 118 · 2019: 101 · 2018: 103 · 2017: 81 · 2016: 83 · 2015: 103 · 2014: 76 · 2013: 9
- FWCI
- 66.57
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (UL1TR000067)
- National Institute of Mental Health (1K23 MH-094707, R01MH081870, K23MH094707)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ketamine, treatment-resistant depression, major depressive disorder, antidepressant efficacy, NMDA receptor antagonism, glutamate, rapid antidepressant response, intravenous infusion, depression severity
- MeSH terms
- Adult, Antidepressive Agents, Major Depressive Disorder, Double-Blind Method, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Personality Inventory, Psychometrics, Excitatory Amino Acid Antagonists, Depressive Disorder, Treatment-Resistant
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