Preliminary evidence that serum interleukin-6 is a candidate biomarker of response to esketamine in treatment-resistant depression.
Marco Colizzi, Elisa Morandin, Veronica Croccia, Claudia Scipioni, Chiara Rosada, Orietta Sepulcri, Matteo Balestrieri, Marco Garzitto
Journal of psychopharmacology (Oxford, England) April 24, 2026 Peer reviewed DOI: 10.1177/02698811261443676 via PubMed
Summary
Higher baseline levels of interleukin-6 (IL-6) are associated with more rapid symptom reduction in treatment-resistant depression (TRD) patients receiving esketamine, while lower IL-6 levels predict greater symptom severity and higher disability. In a 24-week open-label trial with 14 adults, depression severity improved significantly over time, but IL-6 levels did not change significantly during treatment. These findings suggest that IL-6 may serve as a predictor for response to esketamine, indicating the role of inflammation in treatment resistance.
Study at a glance
| Design | open-label Phase 2 trial |
|---|---|
| Sample size | 14 |
| Population | adults with treatment-resistant depression |
| Key finding | Baseline IL-6 may predict response to esketamine in treatment-resistant depression. |
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.