RCT · 2026
Esketamine infusions did not change inflammation markers in depressed teens
- Original title
- Multiple peripheral inflammatory markers in adolescents with major depressive disorder treated with repeated esketamine infusions: results from a randomized controlled trial.
- Authors
- Lan X, Wu Z, Wang C, et al.
- Journal
- Journal of affective disorders, 2026
- Molecules
- Esketamine
- Conditions
- Depression, Suicidal ideation
- Participants
- 49
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does repeated esketamine treatment change markers of inflammation in the blood of adolescents with major depression, and do those markers track symptom change?
What they did
Forty-nine adolescents with major depressive disorder were randomly assigned, with neither they nor the raters knowing the assignment, to receive three infusions of either esketamine or midazolam (a sedative used as a comparison drug) over five days, between December 2020 and April 2022. Researchers measured suicidal thinking with the Columbia Suicide Severity Rating Scale (C-SSRS) and depression with the Montgomery-Asberg Depression Rating Scale (MADRS). They also measured 10 inflammatory markers in plasma at the start, on Day 6 and on Day 12.
What they found
All markers changed significantly over time, but there was no significant difference between the esketamine and midazolam groups for any marker. Within the esketamine group, changes in the marker IL-8 were linked to reductions in C-SSRS Intensity at Day 6 (r = 0.444, p = 0.026), and changes in IFN-gamma were linked to reductions in MADRS (r = 0.399, p = 0.048) and C-SSRS Intensity (r = 0.427, p = 0.033) at Day 12. Higher baseline levels of the marker C4 were linked to smaller reductions in MADRS and in C-SSRS Ideation at Days 6 and 12 (all p < 0.005).
The fine print
The trial was small, with 49 adolescents split across two groups, and follow-up ran only to Day 12. The marker-symptom links were exploratory correlations across 10 markers and several time points, so some may be chance findings, and a correlation does not show cause. The abstract does not report the actual depression or suicidality outcomes between groups, and this summary is based on the abstract alone.
What it means
In this small trial, esketamine did not shift inflammation markers more than the comparison drug, and the suggested biomarkers of response are early-stage leads rather than established tests.
Evidence grade: Low. A small randomized trial (49 teens) reporting exploratory blood-marker analyses with many outcomes and short follow-up, so the correlations are preliminary.
This summary is based on the study’s published abstract.