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 DOI: 10.1177/02698811261443676 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label phase 2 trial Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Adults with treatment-resistant depression |
| Intervention | Intranasal esketamine |
| Duration | 4-week twice-weekly treatment followed by tapering, with assessments at baseline, week 8, and week 24 |
| Topics | Depression Esketamine Ketamine |
| Keywords | Biological predictors Glutamatergic system Inflammation Personalized medicine Psychopharmacology Rapid-acting antidepressant |
| Key findings | Higher baseline IL-6 levels predicted more rapid symptom reduction with esketamine, whereas lower IL-6 predicted greater symptom severity and disability. |
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.
Comparable studies
Other non-randomized and open-label trials on esketamine for depression, most cited first.