Glutamatergic Modulators in Depression

• Published in: Harvard review of psychiatry Vol. 26; no. 6; p. 307
• Main Authors: Henter, Ioline D, de Sousa, Rafael Teixeira, Zarate, Jr, Carlos A
• Format: Journal Article
• Language: English
• Published: United States 01.11.2018
• Subjects: Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Bipolar Disorder - drug therapy; Depressive Disorder, Major - drug therapy; Excitatory Amino Acid Agents - administration & dosage; Excitatory Amino Acid Agents - pharmacology; Humans; Receptors, Metabotropic Glutamate - drug effects; Receptors, N-Methyl-D-Aspartate - drug effects
• ISSN: 1465-7309
• DOI: 10.1097/HRP.0000000000000183

After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).