Potential Antidepressive Effects of R-ketamine in Patients with Treatment Resistance Depression
Sumika Egner
Carleton undergraduate journal of science. May 16, 2025 DOI: 10.22215/cujs.v4i1.4532 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Depression economics Resistance ecology Antidepressant |
| Key findings | R-ketamine showed promising antidepressant-like effects in pre-clinical studies but did not demonstrate consistent significant antidepressant effects in clinical trials for treatment-resistant depression. |
Abstract
Ketamine has a long history as an anesthetic but has recently demonstrated antidepressant effects at sub-anesthetic doses (Matveychuk et al., 2020). For individuals with treatment-resistant depression (TRD), typical antidepressants are frequently ineffective, whereas ketamine’s unique mechanisms have demonstrated promising results in reducing depressive symptoms where other treatments have failed (Voineskos et al., 2020; Matveychuk et al., 2020). Pre-clinical investigation of the ketamine enantiomers, R- and S-ketamine, revealed that R-ketamine may be more effective than S-ketamine due to its rapid-acting, long-lasting antidepressant-like effects with fewer psychotomimetic side effects and abuse liability (Chang et al., 2019; Yang et al., 2015; Bonaventura et al., 2021; Koncz et al., 2023). However, early clinical trials assessing R-ketamine to treat TRD have not yet produced significant antidepressant effects despite promising safety and tolerability profiles (Leal et al., 2023). This review compares the antidepressant efficacy, abuse liability, and safety profiles of ketamine enantiomers, focusing on the antidepressant success of R-ketamine in pre-clinical and clinical trials for TRD. Although R-ketamine did present promising results for treating TRD in pre-clinical trials, it did not demonstrate consistent significant antidepressant effects in clinical trials, making it difficult to conclude its effects in treating depression.
Comparable studies
Other narrative reviews on ketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement | |
| KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS | 2016 | Review | |
| Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors | 2018 | Review | |
| Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder Patients with treatment-resistant depressive symptoms as part of major depressive... | 2018 | Narrative review | |
| Ketamine as a Fast Acting Antidepressant: Current Knowledge and Open Questions | 2013 | Review |