Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression.

Dysfunction of the glutamatergic system is implicated in mood disorders like major depressive disorder and bipolar depression. Subanesthetic-dose ketamine, which modulates glutamatergic signaling, produces rapid reductions in depressive symptoms in clinical studies. This finding has prompted the repurposing and development of other glutamatergic modulators for antidepressant efficacy, either as monotherapy or adjunct to conventional antidepressants. The review highlights evidence for the antidepressant effects of subanesthetic-dose ketamine and other modulators including D-cycloserine, riluzole, CP-101,606, CERC-301, basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide, GLYX-13, and esketamine.

Study at a glance

Abstract

Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review highlights the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine, riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide, GLYX-13, and esketamine.