The R-Stereoisomer of Ketamine as an Alternative for Ketamine for Treatment-resistant Major Depression

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine is one of the most attractive antidepressants for treatment-resistant major depression.1,2) I read the recent article by Murrough et al.3) about the rapid and robust antidepressant effects of a single intravenous infusion of ketamine in treatment-resistant patients with major depression with great interest. In the two-site randomized controlled trial, they used the anesthetic benzodiazepine midazolam as a control drug to optimize their design and mitigate the effects of nonspecific factors on the antidepressant- related outcome. Analysis of the primary outcome measure showed that the ketamine group experienced greater improvement in terms of MontgomeryÅsberg depression rating scale (MADRS) scores than did the midazolam group. Furthermore, the response at 24 hours was also greater in the ketamine than in the midazolam group. Eight (17%) of the 47 patients receiving ketamine experienced significant dissociative symptoms immediately after the ketamine infusion, although these symptoms resolved by 2 hours post-infusion. The relationship between dissociative symptoms and the antidepressant effects of ketamine was not reported. Other common adverse events were observed in both groups. Because of dissociative side effects of ketamine, it is necessary to identify treatment-resistant patients who should not receive ketamine.4)