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Ketamine, a glutamate N-methyl-D-aspartate receptor antagonist, might prove useful for treatment-resistant depression (NEJM JW Psychiatry Dec 28 2012). In this first-ever multisite study, 73 patients with treatment-resistant depression (melancholic features in 65%) stopped all antidepressant medications for at least 1 week and were randomized in a 2:1 ratio to infusion with ketamine or midazolam as a psychoactive placebo.
At 24 hours, depressive symptoms decreased significantly more with ketamine than with midazolam (response rates, 64% vs. 28%). At 7 days, 21 of 47 ketamine patients and 4 of 25 midazolam patients continued to meet response criteria (at 4 weeks, 9 ketamine patients and no midazolam patients). More ketamine patients experienc…