Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology
Yong Wang, Jiangang Xu, Xinyu Zhou, Lu Che, Minghan Qiu, 刘洋 Liu Yang, Ming Gao, Zhen Yang
Advanced Science December 14, 2025 DOI: 10.1002/advs.202516024 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Addiction Ketamine Esketamine |
| Keywords | Perioperative Intensive care medicine Drug Clinical practice Anesthesia Medline Clinical pharmacology |
| Citations | 5 |
| Key findings | Esketamine and ketamine have classical applications in analgesia, sedation, and anesthesia, and emerging effects as antidepressants, anti-tumor, and anti-inflammatory agents, but their use in China is still exploratory and limited by side effects and regulatory controls. |
Abstract
Esketamine and ketamine are perioperative analgesics and anesthetics that have been widely adopted in clinical practice in Europe and the United States. However, their application in China remains in the early stages of exploration and implementation. Esketamine and ketamine exert their effects through multiple receptors and pathways, but primarily act through non-competitive antagonism of the N-methyl-D-aspartate receptor (NMDAR). However, due to their potential side effects and addictive properties, they are subject to certain regulatory controls and are not readily included in routine pharmaceutical use. This review meticulously and systematically synthesizes the latest research progress on Esketamine and ketamine. Their classical applications, including analgesia, sedation, and anesthesia, as well as antidepressant, anti-tumor, and anti-inflammatory effects, are comprehensively covered. By integrating findings from both preclinical and clinical investigations and taking into full account potential limitations, this review aims to provide profound insights that can effectively inform the clinical utilization and future research directions of ketamine and esketamine as versatile therapeutic agents.
Comparable studies
Other narrative reviews on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Can psychedelic compounds play a part in drug dependence therapy? Patients with substance dependency | 2015 | Review | |
| Therapeutic potential of ketamine for alcohol use disorder. | 2021 | Review | |
| Non-parenteral Ketamine for Depression: A Practical Discussion on Addiction Potential and Recommendations for Judicious Prescribing | 2022 | Review | |
| Ketamine, an Old–New Drug: Uses and Abuses | 2023 | Review |
Citations in the library
Cited by 3
- Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence. Pharmaceuticals April 16, 2026
- Esketamine-based PCIA combined with intercostal nerve block for acute pain after lobectomy: a randomized controlled trial Frontiers in Pharmacology March 4, 2026
- Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial. Annals of medicine July 3, 2026
Cites 84
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- 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
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
and 79 more in the library