A Narrative Review: The Role that Ketamine May Play in the Treatment of Depression and the Underlying Mechanisms of Its Effect
Sophie Höfels
BILT Student Research Journal 2025 - Issue 6 July 1, 2025 DOI: 10.70969/20251001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Placebo-controlled Peer reviewed |
|---|---|
| Topics | Ketamine Depression Esketamine |
| Keywords | Depression economics Narrative review Psychotherapist Clinical psychology Literature Keynesian economics |
| Citations | 1 |
| Key findings | A major mechanism contributing to ketamine's antidepressant effects is the reversal of chronic stress pathology present in depression. |
Abstract
The novel antidepressant ketamine has been shown to achieve what most classic antidepressants, such as Selective Serotonin Reuptake Inhibitors, have not been able to. A rapid onset of symptomatic improvement across multiple domains; mood, anhedonia, and suicidal ideation. The exact neuropsychopharmacological mechanisms of this unique phenomenon are still unknown, although many theories are emerging from human and animal studies using neuroimaging and placebo-controlled, cross-over randomised control trials. This review discusses current state-of-the-art theories of action, focussing on neurotransmitter systems, effects of ketamine at the synapse, and functional connectivity in the form of brain networks. These theories are discussed in the context of dysfunctionality in depression, concluding that a major mechanism contributing to ketamine’s antidepressant effects is the reversal of chronic stress pathology present in depression. Possible limitations of evidence presented are discussed.
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 |