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

In adults with treatment-resistant depression, higher baseline levels of the inflammatory marker interleukin-6 (IL-6) were associated with more rapid symptom reduction after intranasal esketamine treatment, while lower IL-6 predicted greater symptom severity and higher disability. IL-6 levels themselves did not change over the 24-week open-label phase 2 trial. The finding suggests that inflammation may play a role in treatment resistance and that baseline IL-6 could help guide personalized treatment decisions.

Study at a glance

Abstract

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. To examine whether baseline IL-6 predicts treatment response to esketamine in individuals with TRD. 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. 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. 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.