A single dose of intravenous ketamine, added to usual care, reduced suicidal thoughts more than the comparison drug midazolam in adults with major depressive disorder and clinically significant suicidal ideation. Twenty-four hours after infusion, suicidal ideation scores dropped by an average of 4.96 points more with ketamine, and 55% of ketamine-treated patients had at least a 50% reduction in suicidal thoughts compared with 30% of those given midazolam. The benefit was partly independent of improvement in depression and lasted up to six weeks with continued pharmacotherapy. Side effects were short-lived. Ketamine appears to rapidly reduce suicidal ideation in depressed patients, though its mechanism remains unclear.
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.