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 DOI: 10.1016/j.jad.2026.122175 via PubMed
Summary
AI-generated from the abstractA midazolam-controlled trial of intravenous ketamine for suicidal depressed patients found that ketamine rapidly reduced suicidal ideation within 24 hours. An exploratory analysis measured saliva cortisol awakening response at baseline and 24 hours after infusion. Waking cortisol significantly increased 24 hours after ketamine treatment. The increase in waking cortisol from baseline to post-infusion showed a small to medium, nonsignificant correlation with decreased suicidal ideation. These preliminary results, pending replication, align with evidence that moderate cortisol increases may enhance stress-resilience.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 61 |
| Population | Suicidal depressed patients |
| Topics | Depression Ketamine |
| Keywords | Cortisol Resilience Stress |
| Key finding | Ketamine treatment produced a significant increase in waking cortisol 24 hours after infusion, but the correlation between this cortisol increase and reduction in suicidal ideation was small to medium and not statistically significant. |
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.