Preliminary evidence that serum interleukin-6 is a candidate biomarker of response to esketamine in treatment-resistant depression.

Abstract

<h4>Background</h4>Interleukin-6 (IL-6) has been implicated as a potential predictor of ketamine response in treatment-resistant depression (TRD). Esketamine, the S-enantiomer of ketamine, produces rapid antidepressant effects and offers improved safety and intranasal administration.<h4>Objective</h4>To examine whether baseline IL-6 predicts treatment response to esketamine in individuals with TRD.<h4>Methods</h4>Fourteen adults with TRD received intranasal esketamine twice weekly for 4 weeks, followed by a tapering phase, in a 24-week open-label Phase 2 trial. Depression severity and functional disability were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and World Health Organization Disability Assessment Schedule at baseline, week 8, and week 24. Serum IL-6 levels were measured at the same time points. Linear mixed-effects models were used to evaluate the predictive value of IL-6.<h4>Results</h4>MADRS scores improved significantly over time. Higher IL-6 levels were associated with more rapid symptom reduction, whereas lower IL-6 predicted greater symptom severity and higher disability. IL-6 levels did not change significantly over the course of treatment.<h4>Conclusions</h4>Baseline IL-6 may predict response to esketamine in TRD, highlighting the potential role of inflammation in treatment resistance and supporting biomarker-guided personalized interventions.

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