Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential.

Depression is a common and long-lasting mental disorder with many interconnected biological pathways. Recent research has found that ketamine, a drug that blocks NMDA receptors, can produce rapid antidepressant effects, offering a new approach to treating mood disorders. This review summarizes current knowledge about signaling pathways and systems involved in depression, drawing from studies of patients and animal models. It focuses on how ketamine works as a fast-acting antidepressant and discusses its potential for preventing or treating stress-related psychiatric conditions.

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Abstract

Depression represents a prevalent and enduring mental disorder of significant concern within the clinical domain. Extensive research indicates that depression is very complex, with many interconnected pathways involved. Most research related to depression focuses on monoamines, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, tryptophan metabolism, energy metabolism, mitochondrial function, the gut-brain axis, glial cell-mediated inflammation, myelination, homeostasis, and brain neural networks. However, recently, Ketamine, an ionotropic N-methyl-D-aspartate (NMDA) receptor antagonist, has been discovered to have rapid antidepressant effects in patients, leading to novel and successful treatment approaches for mood disorders. This review aims to summarize the latest findings and insights into various signaling pathways and systems observed in depression patients and animal models, providing a more comprehensive view of the neurobiology of anxious-depressive-like behavior. Specifically, it highlights the key mechanisms of ketamine as a rapid-acting antidepressant, aiming to enhance the treatment of neuropsychiatric disorders. Moreover, we discuss the potential of ketamine as a prophylactic or therapeutic intervention for stress-related psychiatric disorders.