In a randomized, midazolam-controlled trial of 40 suicidal, depressed participants given intravenous ketamine, acute dissociative and psychotomimetic effects were not associated with changes in suicidal ideation or depressive symptoms from before to after infusion. Norketamine showed a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection, suggesting dissociation may be more an effect of the parent drug. Dehydronorketamine correlated with dissociative symptoms at multiple time points. No evidence was found that ketamine's acute, transient dissociative or psychotomimetic effects contribute to its antidepressant or anti-suicidal actions.
A 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.