The application of esketamine in cancer-related depressive states: attention from mechanisms to clinical translation.

Abstract

<h4>Objectives</h4>This article reviews the clinical status and treatment challenges of cancer-related depressive states, clarifies the mechanism of action of esketamine-a novel rapid-acting antidepressant-compares its efficacy with traditional drugs, evaluates safety and tolerability, and summarizes clinical evidence to support clinical practice and research.<h4>Methods</h4>By searching databases such as PubMed, Web of Science, and Cochrane Library, We conducted a structured review of the available literature on the mechanism of esketamine in the treatment of cancer-related depressive states in recent years, including mechanism studies, clinical trials, and review articles. We focused on its regulation of NMDA receptors, the impact on BDNF expression, synaptic plasticity, and neural circuit remodeling, and compared its efficacy and safety with traditional antidepressants.<h4>Results</h4>Esketamine exerts rapid antidepressant effects via multiple mechanisms: NMDA receptor antagonism, downstream signaling modulation, BDNF upregulation, synaptic plasticity enhancement, and neural circuit remodeling. Available studies suggest that esketamine may provide rapid antidepressant effects in oncology populations, particularly in perioperative settings. Common adverse events-such as transient dissociation and elevated blood pressure-are generally controllable.<h4>Conclusions</h4>Esketamine, as a rapidly acting antidepressant, has a plausible mechanistic rationale and potential clinical value in the treatment of cancer-related depressive states. However, its long-term safety, optimal dosing regimens, and individualized application in different cancer patients still require further investigation. In the future, the integration of multi-omics technologies and clinical translational research should be promoted to advance the precision and standardization of its application in cancer-related depressive states treatment.

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