Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, MD, 20892, USA. mark.kvarta@nih.gov.
2 papers in the library · 19 citations · publishing 2024-2026
Esketamine, the (S)-enantiomer of racemic ketamine, is an FDA-approved rapid-acting antidepressant for treatment-resistant depression (TRD) that outperforms traditional oral antidepressants. Research on biomarkers predicting response to esketamine remains limited and mostly extrapolated from racemic ketamine studies. Genetic, proteomic, and metabolomic profiles suggest inflammation and mitochondrial function may contribute to its effects, but these findings require verification. Neuroimaging consistently implicates the prefrontal cortex, striatum, and anterior cingulate cortex. In perioperative settings, esketamine reduces depression and anxiety, correlating with increased brain-derived neurotrophic factor and serotonin. Better-designed biomarker-focused clinical trials are needed to clarify mechanisms and identify patients most likely to benefit.
People with both major depression and post-traumatic stress disorder (PTSD) have lower baseline levels of copeptin, a stable marker of vasopressin secretion, and a blunted reduction in copeptin after a single low-dose ketamine infusion compared to those with depression alone. Copeptin levels were unrelated to depression diagnosis or symptom severity of depression, anxiety, PTSD, anhedonia, suicidal ideation, or childhood trauma, but higher copeptin was linked to verbal aggression, an association weakened by PTSD. These findings point to a possible biological subtype of reduced vasopressin activity in co-occurring depression and PTSD, suggesting copeptin may serve as a peripheral biomarker for central vasopressin-driven circuits in neuropsychiatric disorders.