Investigation of Potential Therapeutic Effects of New Rapid-Acting Antidepressant Drugs (RAADs) Using Stress-Based Models of Depression
Biomolecules August 24, 2026 DOI: 10.3390/biom16091230 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression |
| Key findings | The review argues that ketamine's rapid antidepressant effects and distinctive behavioral profile in screening tests and animal models offer a new paradigm for discovering rapid-acting antidepressants. It emphasizes that traditional screening approaches, designed for conventional antidepressants, may not fully capture the mechanisms of rapid-acting drugs. |
Abstract
The use of animal models to study mental illnesses, such as depression, requires proper standardization and extensive expertise. Achieving good construct, face, and predictive validity in depression models is quite challenging. Currently, only a few environmental models, mostly based on chronic stress, and a limited number of genetic models fulfill these criteria. In the quest for new antidepressants, initial screening tests are employed as a preliminary step in research. While these tests do not always meet the requirements of a disease model, they are useful for the early identification of substances that may have antidepressant potential, paving the way for further studies based on established models. This approach to discovering antidepressants was originally designed for traditional medications, which typically act by modulating serotonergic, noradrenergic, and dopaminergic systems, and require multi-week administration to produce a therapeutic effect. In contrast, the new antidepressant ketamine offers rapid therapeutic effects following a single dose and exhibits distinctive behavioral outcomes in both screening tests and animal depression models. These effects have inspired a new model for the search for rapid-acting ketamine-like antidepressants. This review presents the behavioral effects of ketamine and discusses the methodologies used in the search for novel rapid-acting antidepressant drugs (RAADs).
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | 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 | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 24
- 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
- Classical psychedelics for the treatment of depression and anxiety: A systematic review. Journal of Affective Disorders November 1, 2019
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine. Pharmacology, Biochemistry, and Behavior June 1, 2019
and 19 more in the library