Oxidative stress (OS) is increasingly recognized not only as a factor in depressive disorders but also as a potential biomarker for the severity and persistence of treatment-resistant depression (TRD). This review synthesizes current evidence linking OS to TRD's chronicity and symptom persistence, suggesting that OS severity may indicate treatment resistance. The authors discuss fast-acting antidepressants and a non-pharmacological nutraceutical approach aimed at reducing OS as a way to fill a therapeutic gap and improve recovery chances. An integrated strategy to lower OS may help overcome treatment resistance in severe TRD, modifying disease course and improving prognosis.
Ketamine at 25 ng/mL increased the viability of mouse hippocampal HT22 neuronal cells exposed to hydrogen peroxide, but only at the highest concentration tested (1000 µM H₂O₂). At that level, cell viability rose from 12% (±1.63%) without ketamine to 38% (±9.12%) with ketamine. This suggests a protective, nonlinear effect that depends on the intensity of oxidative stress, activating only at critical H₂O₂ overload typical of severe depression. The findings indicate a threshold antioxidant mechanism that may contribute to ketamine's antidepressant action and inform future predictive models for individualized treatment.