A single intravenous infusion of ketamine produced greater improvement in depression severity 24 hours later than the active placebo midazolam in patients with treatment-resistant major depression. In a randomized controlled trial of 73 participants, the ketamine group scored 7.95 points lower on the Montgomery-Åsberg Depression Rating Scale than the midazolam group. Response rates were 64% for ketamine and 28% for midazolam, with an odds ratio of 2.18 favoring ketamine. The findings support NMDA receptor modulation as a mechanism for rapid improvement in severe, chronic depression, though more information on durability and safety is needed before clinical use.
A single subanesthetic dose of intravenous ketamine reduced explicit suicidal thoughts and implicit associations between self and escape in adults with treatment-resistant major depression more than the active placebo midazolam. Twenty-four hours after infusion, 53% of ketamine-treated patients scored zero on all three explicit suicide measures, compared with 24% of the midazolam group. The reductions in explicit suicidal cognition were largest in those with higher baseline suicidal thoughts and were partly explained by decreases in other depressive symptoms. The findings suggest ketamine may offer rapid relief from suicidal cognition beyond what a psychoactive placebo provides.
Ketamine, an NMDA receptor antagonist, has antidepressant and antisuicidal effects shown over the past two decades and is effective for treatment-resistant depression. The FDA has approved intranasal (S)-ketamine with an oral antidepressant for this condition. However, the need for in-office administration and monitoring limits accessibility, and concerns about risks and abuse potential remain. Despite these drawbacks, its potential efficacy makes it a useful treatment for patients with treatment-resistant depression and suicidality.