RCT · 2026
Morning cortisol rose 24 hours after ketamine in a trial for suicidal depression
- Original title
- Increased morning cortisol after ketamine treatment for suicidal depression: Exploratory report from a randomized trial.
- Authors
- Choo TH, Galfalvy HC, Keilp JG, et al.
- Journal
- Journal of affective disorders, 2026
- Molecules
- Ketamine
- Conditions
- Depression, Suicidal ideation
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does a single intravenous dose of ketamine change the body’s morning stress-hormone response in depressed people with suicidal thoughts, and does that change track with improvement?
What they did
The researchers ran a clinical trial comparing a low (subanesthetic) intravenous dose of ketamine with midazolam, a sedative used as a comparison drug. In this add-on analysis, participants gave saliva samples on waking and 30 minutes later, both before the infusion and 24 hours afterwards. Saliva was tested for cortisol, a hormone released by the body’s stress-response system, which is often disrupted in depression and suicidal states.
What they found
Waking cortisol was significantly higher 24 hours after ketamine treatment than before it (t(61) = -3.15, p = 0.0025). The rise in waking cortisol showed a small-to-medium correlation with a drop in suicidal ideation, but this did not reach statistical significance (r = -0.25, p = 0.052). The authors describe the findings as preliminary and needing replication.
The fine print
This was an exploratory aim of the trial, not its main question, so the results are hypothesis-generating rather than conclusive. The abstract does not report the number of participants, the comparison of cortisol change between ketamine and midazolam groups, or follow-up beyond 24 hours. Cortisol is a biological marker, not a measure of how someone feels, and the link to reduced suicidal thinking was not statistically significant. This summary is based on the abstract only.
What it means
Ketamine appeared to shift the body’s morning stress-hormone pattern within a day, but whether that shift explains any improvement in suicidal thinking remains unproven.
Evidence grade: Low. This is an exploratory, secondary analysis within a randomized trial, using a biological marker rather than a clinical outcome, and the key correlation was not statistically significant.
This summary is based on the study’s published abstract.