Ketamine and Esketamine in Depression: Current Evidence on Mechanisms, Efficacy, Safety and Clinical Use – A Review
Urszula Szuleta, Wiktoria Zawada, Krystian Kaczmarek, Zofia Jadwiga Leszczyńska, Vladyslav Romaniuk, Agnieszka Benecka, Jakub Pietrończyk, Alicja Benecka, Zuzanna Wieczorek, Iga Tartas, Natalia Prankiewicz
Journal of Education Health and Sport June 22, 2026 Peer reviewed DOI: 10.12775/jehs.2026.93.72419 via OpenAlex
Summary
Ketamine shows promise as a treatment for drug-resistant and severe depression due to its rapid onset of action. Current evidence suggests it may help reduce suicidal ideation in high-risk patients, but there is a need for more large-scale, long-term studies to determine the durability of its benefits and its long-term safety. The cumulative remission rate for traditional antidepressants is about 41% after four treatment steps, indicating limitations in current therapies.
Study at a glance
| Design | review |
|---|---|
| Population | patients with major depressive disorder, particularly those with treatment-resistant depression |
| Key finding | Ketamine may be an effective option for treating drug-resistant and severe depression, with some evidence of reducing suicidal ideation. |
Abstract
Introduction and purpose. Major depressive disorder is a serious clinical problem. Current treatments are often unsuccessful, and many patients do not achieve full remission. In a reanalysis of the STAR*D study, the cumulative remission rate after up to four treatment steps was about 41%, which highlights the limitations of currently available antidepressant strategies[1]. In recent years, growing attention has been paid to novel agents with potential rapid antidepressant effects. Among them, ketamine and its derivatives have become the subject of numerous studies evaluating their role in depressive disorders, particularly in treatment-resistant depression [2]. The aim of this review is to summarize current evidence regarding the efficacy, safety, and clinical use of ketamine and its derivatives in depression, with particular emphasis on treatment-resistant depression. A brief description of the state of knowledge. This review presents current evidence on novel therapeutic agents that may be useful in the treatment of severe depression. It discusses the concept of severe depression and its broader clinical and social consequences. Particular attention is given to the mechanisms of action of ketamine and its derivatives, the available evidence on their efficacy, their adverse effects, and their potential impact on suicidal ideation. The review also emphasises the limitations of existing data and the need for further research. Summary (conclusions). Current data indicate that ketamine is a promising option for the treatment of drug-resistant and severe depression because of its rapid onset of action. Some evidence suggests that it may reduce suicidal ideation in high-risk patients, however further large-scale, long-term studies are needed to clarify the durability of benefit and long-term safety. [2,3,4].