Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.
Yingliang Dai, Ben J. Harrison, Christopher G. Davey, Trevor Steward
The International Journal of Neuropsychopharmacology February 4, 2025 DOI: 10.1093/ijnp/pyaf010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Neurocognitive Depression/mental-health/mood-disorders Ketamine/psychopharmacology/antidepressants Neuroscience/neurobiology/brain-research |
| Citations | 6 |
| Key findings | Ketamine's antidepressant effects are driven by modulation of brain systems supporting reward processing, interoception, and self-related cognition. |
Abstract
Ketamine is an N-methyl-D-aspartate receptor antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine's antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less clearly understood. To help provide such a framework, we provide a synthesis of current evidence linking ketamine treatment to the modulation of brain systems supporting reward processing, interoception, and self-related cognition. We suggest that ketamine's antidepressant effects are, at least in part, driven by dynamic multi-level influences across these key functional domains.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 3
- Ketamine as a potential cognitive enhancer in neurological disorders: evidence from preclinical and clinical studies Frontiers in Neurology March 30, 2026
- Mindfulness, music, visual occlusion in ketamine therapy for depression: do they change outcomes? A qualitative and quantitative analysis of a randomized controlled trial Frontiers in Psychiatry September 2, 2025
- Body image phenomenology in reports of psychedelic and meditative experiences: main themes and associations with body attitudes. Neuroscience of Consciousness 2026
Cites 51
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- 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
- Interoceptive inference, emotion, and the embodied self Trends in Cognitive Sciences October 12, 2013
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
and 46 more in the library