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.
In patients with treatment-resistant depression, ketamine increased blood levels of brain-derived neurotrophic factor (BDNF) in those who responded to the drug, compared to non-responders, 240 minutes after infusion. Higher BDNF levels were strongly linked to lower depression scores at multiple time points up to 72 hours. No such associations appeared in patients given the anesthetic midazolam. The findings support BDNF as a marker of ketamine's antidepressant effects.
Ketamine given intravenously at 0.5 mg/kg over 40 minutes was safe and well tolerated in a large group of patients with treatment-resistant depression. Across 205 infusions in 97 participants, the antidepressant response rate was 67%. Only about 2% of infusions were stopped due to adverse effects, and the overall dropout rate was 3%. Common temporary side effects in the first four hours included drowsiness, dizziness, poor coordination, blurred vision, and feeling strange or unreal. About one third of participants had changes in blood pressure or heart rate. There were small but significant increases in psychotomimetic and dissociative symptoms, but no lasting psychotic effects, medical complications, or increased substance use among those followed long-term.