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.
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.