Antidepressant actions of ketamine: from molecular mechanisms to clinical practice
Open accessAbstract
In the past decade the emergence of glutamate N-methyl-d-aspartate (NMDA) receptor blockers such as ketamine as fast-acting antidepressants fostered a major conceptual advance by demonstrating the possibility of a rapid antidepressant response. This discovery brings unique mechanistic insight into antidepressant action, as there is a substantial amount of basic knowledge on glutamatergic neurotransmission and how blockade of NMDA receptors may elicit plasticity. The combination of this basic knowledge base and the growing clinical findings will facilitate the development of novel fast acting antidepressants.
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Ketamine is effective for treatment-refractory symptoms including suicidality, anxiety, and anhedonia, and it affects motivation-related functional circuits.
“ketamine has been found to be effective for traditionally treatment-refractory symptoms such as suicidality, anxiety, and anhedonia, and to impact functional circuitries related to motivation [8,9].”
From Ketamine in neuropsychiatric disorders: an update (2024) · cites this paper as [8]
The Introduction (page not supplied) reports a rapid antidepressant response in treatment-resistant depression and rapid antisuicidal effects. It does not report efficacy for anxiety or anhedonia, or an effect on motivation-related functional circuits. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSimilar results in BDNF mRNA and TrkB phosphorylation have been observed after acute treatment with ketamine.
“Similar results in BDNF mRNA and TrkB phosphorylation have been observed after acute treatment with ketamine [216,217,218,219].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [218]
The ‘Synaptic and neuronal basis of ketamine action’ section describes ketamine-associated BDNF upregulation through protein translation, but does not report an increase in BDNF mRNA. The ‘NMDA receptor blocker memantine does not elicit a rapid antidepressant effect’ section discusses TrkB signaling and phosphorylation of mTOR, not observed TrkB phosphorylation after acute ketamine treatment. No page numbers are available in our copy. (LLM, conf=0.82)
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- Authors
- Monteggia, L. M., & Zarate, C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- National Institutes of Health (US)
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 30
- Pages
- 139-143
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC4343533
- OpenAlex
- W1984167101
- Cited by
- 149
- References
- 50
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 21 · 2017: 18 · 2016: 25 · 2015: 15
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH070727)
- Intramural Research Program of the National Institute of Mental Health/National Institutes of Health
- National Alliance for Research on Schizophrenia and Depression Independent Investigator Award
- Brain and Behavior Foundation Award
- International Mental Health Research Organization
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- ketamine, rapid-acting antidepressants, NMDA receptor antagonism, glutamatergic neurotransmission, synaptic plasticity, antidepressant mechanism, depression treatment
- MeSH terms
- Antidepressive Agents, Clinical Trials as Topic, Depression, Humans, Ketamine, Receptors, N-Methyl-D-Aspartate
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