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Cited by 418Treatment of Major DepressionElectroconvulsive Therapy StudiesTranscranial Magnetic Stimulation Studies

Ketamine for Depression: Where Do We Go from Here?

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aan het Rot, Marije, Zarate, Carlos A., Charney, Dennis S., Mathew, Sanjay J.·2012·Biological Psychiatry
DOI 10.1016/j.biopsych.2012.05.003PMC PMC3438349
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Abstract

Since publication of the first randomized controlled trial describing rapid antidepressant effects of ketamine, several reports have confirmed the potential utility of this dissociative anesthetic medication for treatment of major depressive episodes, including those associated with bipolar disorder and resistant to other medications and electroconvulsive therapy. These reports have generated several questions with respect to who might respond to ketamine, how, and for how long. To start answering these questions. We used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant effects of ketamine and of all recently completed, ongoing, and planned studies. To date, 163 patients, primarily with treatment-resistant depression, have participated in case studies, open-label investigations, or controlled trials. All controlled trials have used a within-subject, crossover design with an inactive placebo as the control. Ketamine administration has usually involved an anaesthesiologist infusing a single, subanesthetic, intravenous dose, and required hospitalization for at least 24 hours postinfusion. Response rates in the open-label investigations and controlled trials have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours postinfusion. Although adverse effects have generally been mild, some patients have experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk-benefit analyses support further research of ketamine for individuals with severe mood disorders. However, given the paucity of randomized controlled trials, lack of an active placebo, limited data on long-term outcomes, and potential risks, ketamine administration is not recommended outside of the hospital setting.

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  • Ketamine is now FDA-approved for depression as intranasally delivered S-ketamine.

    “Currently, the most widely prescribed psychedelic-related compound is ketamine, a noncompetitive antagonist of NMDARs that has been used safely at high doses as an anesthetic for decades, and is now FDA-approved for depression (intranasally delivered S-ketamine) (Aan Het Rot et al., 2012;Krystal et al., 2019).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Aan Het Rot et al., 2012

    The Discussion’s conclusion describes ketamine treatment for depression as “off-label,” rather than approved. The Results section on ongoing studies says intranasal ketamine was being investigated and S-ketamine was not; this 2012 paper therefore does not support the attributed FDA-approval claim. (LLM, conf=0.86)

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  • Ketamine is a noncompetitive antagonist of NMDARs.

    “Currently, the most widely prescribed psychedelic-related compound is ketamine, a noncompetitive antagonist of NMDARs that has been used safely at high doses as an anesthetic for decades, and is now FDA-approved for depression (intranasally delivered S-ketamine) (Aan Het Rot et al., 2012;Krystal et al., 2019).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Aan Het Rot et al., 2012

    The Abstract (page not provided) states that ketamine primarily acts as an NMDA-receptor antagonist at the dose discussed. It does not specify that the antagonism is noncompetitive, so that part of the attributed claim is not supported by our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Ketamine has been used safely at high doses as an anesthetic for decades.

    “Currently, the most widely prescribed psychedelic-related compound is ketamine, a noncompetitive antagonist of NMDARs that has been used safely at high doses as an anesthetic for decades, and is now FDA-approved for depression (intranasally delivered S-ketamine) (Aan Het Rot et al., 2012;Krystal et al., 2019).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Aan Het Rot et al., 2012

    The ECT and Ketamine Anesthesia section (page unavailable) says ketamine is occasionally used for anesthesia during ECT. The copy does not establish that high-dose anesthetic use has been safe for decades; its safety discussion instead describes monitoring and potential medical complications. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
aan het Rot, M., Zarate, C. A., Charney, D. S., & Mathew, S. J.
Affiliations
  • National Institute of Mental Health (US)
  • Icahn School of Medicine at Mount Sinai (US)
  • Michael E. DeBakey VA Medical Center (US)
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2012-10
Volume
72
Issue
7
Pages
537-547
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2012.05.003
PMC
PMC3438349
OpenAlex
W2044325416
Cited by
418
References
5
Citations by year
2026: 6 · 2025: 12 · 2024: 19 · 2023: 22 · 2022: 25 · 2021: 13 · 2020: 30 · 2019: 20 · 2018: 40 · 2017: 23 · 2016: 43 · 2015: 58 · 2014: 54 · 2013: 38 · 2012: 13
FWCI
5.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (R01MH81870)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • 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, treatment-resistant depression, major depressive episode, bipolar disorder, antidepressant effects, dissociative anesthetics, response rate, adverse effects, risk-benefit assessment, long-term outcomes, hospitalization
MeSH terms
Animals, Antidepressive Agents, Depression, Humans, Ketamine, Databases, Factual

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