Multiple peripheral inflammatory markers in adolescents with major depressive disorder treated with repeated esketamine infusions: results from a randomized controlled trial.
Xiaofeng Lan, Zitao Wu, Chengyu Wang, Guanxi Liu, Muqin Zhang, Weicheng Li, Zhanjie Luo, Junhao Shen, Ziying Chen, Yuping Ning, Yanling Zhou
Journal of Affective Disorders February 23, 2026 DOI: 10.1016/j.jad.2026.121488 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind trial Peer reviewed |
|---|---|
| Sample size | 49 |
| Population | Adolescents with major depressive disorder |
| Interventions | Esketamine Midazolam |
| Duration | Three infusions over five days; assessments at baseline, Day 6, and Day 12 |
| Measures | Columbia Suicide Severity Rating Scale (C-SSRS), Montgomery-Åsberg Depression Rating Scale (MADRS), plasma levels of 10 inflammatory markers |
| Topics | Depression Esketamine Ketamine |
| Keywords | Humans Inflammation Midazolam Antidepressive agents Interleukin-8 Cytokines Double-blind method Adolescent Female Suicidal ideation Biomarkers |
| Key findings | Esketamine and midazolam did not differ significantly in their effects on 10 inflammatory markers; most changes reflected time effects in both groups. In the esketamine group, changes in IL-8 correlated with reduced suicidal ideation intensity at Day 6, and changes in IFN-γ correlated with reduced depression severity and suicidal ideation intensity at Day 12. Baseline C4 was negatively related to symptom reductions. The authors propose IL-8, IFN-γ, and C4 as candidate biomarkers warranting further study. |
Abstract
Objective: While inflammatory dysregulation is well-documented in major depressive disorder (MDD), its response to esketamine treatment in adolescents remains poorly understood. We aimed to examine the effects of esketamine on the inflammatory cytokines in adolescent MDD.
Methods: This randomized, double-blind trial assigned 49 adolescents with MDD to receive three infusions of esketamine or midazolam over five days between December 2020 and April 2022. Suicidal ideation (measured by Columbia Suicide Severity Rating Scale, C-SSRS), depressive symptoms (measured by Montgomery-Åsberg Depression Rating Scale, MADRS) and plasma levels of 10 inflammatory markers were assessed at baseline, Day 6, and Day 12.
Results: Linear mixed model revealed significant time effects for all markers, but no significant drug main effect was observed. In esketamine group, alterations in IL-8 were associated with the reduction of C-SSRS Intensity at Day 6 (r = 0.444, p = 0.026), and alterations in IFN-γ were correlated with the reduction of MADRS (r = 0.399, p = 0.048) and C-SSRS Intensity (r = 0.427, p = 0.033) at Day 12. Baseline C4 negatively related to the reductions of MADRS and C-SSRS Ideation at Day 6 and 12 (all p < 0.005).
Conclusions: Our study found no significant drug main effects for inflammatory markers, with most changes representing time effects observed in both groups. Exploratory results indicate that IL-8, IFN-γ, and C4 may warrant further investigation as potential biomarkers of esketamine response in adolescent MDD.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.