Clinical, Metabolic and Inflammatory Indicators of Esketamine Efficacy for Treatment-Resistant Major Depressive Episodes

Abstract

Major depressive disorder (MDD) is a common and debilitating condition. When it becomes difficult to treat, it poses a significant challenge. Individuals with treatment-resistant depression (TRD) often experience severe symptoms and elevated suicide risk. Metabolic and inflammatory abnormalities may contribute to inadequate response to treatments. Esketamine has demonstrated promise in TRD, but its biological effects and predictors of response remain poorly understood. This study examined clinical outcomes and metabolic and inflammatory biomarkers in individuals with TRD receiving esketamine. Participants underwent four weeks of twice-weekly intranasal esketamine, completed rater-administered and self-reported measures, and provided blood samples for biomarker analysis. Esketamine was associated with reductions in depressive symptoms and suicidal ideation. Higher fasting glucose pre-treatment predicted greater reductions in suicidal ideation. Decreases in fasting glucose and systolic blood pressure were observed post-treatment. These findings support the therapeutic effects of esketamine and emphasize the need for further investigation into its broader biological impacts.