Background: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression.
Methods: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions.
Results: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment).
Conclusions: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.