Prophylactic Ketamine: Current Knowledge and Future Directions.
Astrid M Cardona-Acosta, Lyonna F Parise, Carlos A. Bolaños-Guzmán, Eric M Parise
Biological Psychiatry March 28, 2025 DOI: 10.1016/j.biopsych.2025.03.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine (R S)-ketamine (2R (2S 6S)-hydroxynorketamine |
| Topics | Ketamine Esketamine |
| Keywords | Neuroprotective drugs Prophylactic treatment Stress resilience Stress-induced psychiatric disorders Ketamine therapy Neuroprotection Preventive psychiatry Stress management Mental health interventions |
| Citations | 2 |
| Key findings | Ketamine shows potential as a prophylactic for stress-induced disorders, but further research is needed to understand its benefits and risks. |
Abstract
The prevalence of stress-induced disorders, including depression, anxiety, posttraumatic stress disorder, and postpartum depression, has been increasing, while current treatment approaches are limited. As a result, researchers are exploring alternative treatments that include ketamine as a prophylactic against these disorders. This review provides an overview of the current knowledge on the use of ketamine as a prophylactic for stress-induced disorders, including preclinical and clinical findings on (R,S)-ketamine, as well as (2R,6R)- and (2S,6S)-hydroxynorketamine. We also explore the potential underlying mechanisms involved in preventing these disorders, including the brain regions/circuits, as well as glutamatergic, dopaminergic, serotonergic, and inflammatory processes known to be involved, as evidenced by studies with ketamine and its metabolites. Additionally, we highlight the limitations and risks associated with ketamine use, such as age- and sex-specific efficacy, potential long-term and adverse effects, and legal and ethical considerations. Finally, we discuss future research directions, including the implications for clinical practice, integrating ketamine into current treatment approaches, and potential advancements in ketamine-based therapies. Overall, the literature emphasizes the importance of continuing research to better understand the potential benefits and risks of ketamine as a prophylactic for stress-induced disorders.
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 55
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
and 50 more in the library