Commentary |

N- methyl-D-aspartate Glutamate Receptor Antagonists and the Promise of Rapid-Acting Antidepressants

John H. Krystal, MD
Arch Gen Psychiatry. 2010;67(11):1110-1111. doi:10.1001/archgenpsychiatry.2010.138.
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The exciting findings reported by Diazgranados and her collagues1 regarding the antidepressant efficacy of the uncompetitive N- methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine in depressed patients with bipolar disorder add to the emerging interest in rapid-acting antidepressants (RAAs).

Their article describes robust, clinically relevant, and rapid alleviation of depression symptoms in patients with bipolar disorder that persists far beyond the presence of the drug in the body. Ketamine has a terminal half-life of approximately 3 hours. Yet after 2 days, or 16 half-lives, of ketamine, the effect size of its antidepressant effects was large (0.8). Impressively, at 2 weeks there were still traces of the antidepressant effects of single ketamine dose, associated with an effect size of 0.22. Further, 6 of 17 patients had a clinical response to ketamine within 40 minutes of infusion and 9 of 16 patients experienced a remission of their depression during the study. The magnitude of these ketamine effects was particularly impressive because the changes were observed in patients who had treatment-resistant symptoms and who were already receiving mood-stabilizing medications. These data suggest that the benefits of ketamine in patients with bipolar disorder mirror those reported earlier for patients with unipolar depression.24

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