Novel mechanisms underlying rapid-acting antidepressants: ketamine-like compounds, neurosteroid GABAkines, and psychedelics.
Sara Castanheira, Catarina Vale Gomes, Joana Bicker, Ana Fortuna
Drug Discovery Today June 1, 2025 DOI: 10.1016/j.drudis.2025.104371 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Bdnf Gaba Psychedelics Rapid-acting antidepressant drug Depression treatment Neuroscience research Antidepressant drugs Brain chemistry Mental health therapy |
| Citations | 9 |
| Key findings | Rapid-acting antidepressant drugs primarily work by potentiating BDNF or activating GABAA receptors. |
Abstract
The discovery of the rapid antidepressant action of ketamine accelerated the identification of new molecules that are associated with fast and prolonged relief of depressive symptoms. As a result, a new group of antidepressants have emerged, some of them already approved for clinical use, classified as rapid-acting antidepressant drugs (RAADs). Potentiation of brain-derived neurotrophic factor (BDNF) or activation of the GABAA receptors are the main mechanisms behind the notable properties of RAADs, a mainstream topic in the field of pharmacology and drug discovery that deserves an updated review.
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
Cites 32
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. New England Journal of Medicine November 3, 2022
and 27 more in the library