Increased morning cortisol after ketamine treatment for suicidal depression: Exploratory report from a randomized trial.
Tse-Hwei Choo, Hanga C Galfalvy, John G Keilp, Ainsley K Burke, J John Mann, Michael F Grunebaum
Journal of affective disorders November 1, 2026 Peer reviewed DOI: 10.1016/j.jad.2026.122175 via PubMed
Summary
A clinical trial of intravenous ketamine infusion for suicidal depressed patients showed a rapid reduction in suicidal ideation within 24 hours. Saliva cortisol analysis indicated a significant increase in waking cortisol levels after treatment. However, the correlation between the change in cortisol and decrease in suicidal ideation was small to medium and nonsignificant. These findings suggest that increases in cortisol may enhance stress resilience, but further research is needed.
Study at a glance
| Design | clinical trial |
|---|---|
| Sample size | 62 |
| Population | suicidal depressed patients |
| Key finding | A significant increase in waking cortisol was observed 24 hours after ketamine treatment. |
Abstract
Depression and its severe outcomes, suicidal ideation and behavior, are exacerbated by stress. A broad literature links dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) stress response system to depression, suicidal ideation and behavior. Our midazolam-controlled clinical trial of subanesthetic, intravenous ketamine infusion for suicidal depressed patients found rapid reduction in suicidal ideation within 24 h. Here we report on an exploratory aim of the trial to investigate relationships of treatment effect and clinical response to HPA axis function via saliva cortisol analysis. Saliva cortisol awakening response was measured at baseline/pre-infusion and 24 h after with samples obtained upon morning awakening and 30 min later. A significant increase in waking cortisol 24 h after ketamine treatment was observed (t(61) = -3.15, p = 0.0025). Baseline to post-infusion increase in waking cortisol had a small to medium, nonsignificant, correlation with decrease in SI (r = -0.25, p = 0.052). These preliminary results need to be replicated but are consistent with studies suggesting increases in cortisol, if not excessive or prolonged, may enhance stress-resilience.