Novel Insights Into the Neurobiology of the Antidepressant Response From Ketamine Research: A Mini Review
Michael Colla, Hanne Scheerer, Steffi Weidt, Erich Seifritz, Golo Kronenberg
Frontiers in Behavioral Neuroscience December 3, 2021 DOI: 10.3389/fnbeh.2021.759466 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Serotonin Esketamine |
| Keywords | Monoaminergic Antidepressant Disinhibition Glutamatergic Hippocampus Glutamate receptor |
| Citations | 9 |
| Key findings | Ketamine produces rapid antidepressant effects through mechanisms beyond monoaminergic signaling, but has not yet yielded new therapies beyond ketamine itself. |
Abstract
The serendipitous discovery of ketamine's antidepressant effects represents one of the major landmarks in neuropsychopharmacological research of the last 50 years. Ketamine provides an exciting challenge to traditional concepts of antidepressant drug therapy, producing rapid antidepressant effects seemingly without targeting monoaminergic pathways in the conventional way. In consequence, the advent of ketamine has spawned a plethora of neurobiological research into its putative mechanisms. Here, we provide a brief overview of current theories of antidepressant drug action including monoaminergic signaling, disinhibition of glutamatergic neurotransmission, neurotrophic and neuroplastic effects, and how these might relate to ketamine. Given that research into ketamine has not yet yielded new therapies beyond ketamine itself, current knowledge gaps and limitations of available studies are also discussed.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 6
- Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation CNS Drugs January 22, 2023
- Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks. Molecules June 30, 2025
- EEG vigilance and response to oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized validation study. Psychiatry Research Neuroimaging July 1, 2025
- Ketamine as a Mental Health Treatment AJN, American Journal of Nursing February 19, 2026
- Resting-State Electroencephalogram Complexity Is Associated With Oral Ketamine Treatment Response: A Bayesian Analysis of Lempel-Ziv Complexity and Multiscale Entropy. Brain and Behavior November 1, 2024
and 1 more in the library
Cites 33
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
and 28 more in the library