Glutamatergic Modulators in Depression
Ioline D. Henter, Rafael Teixeira de Sousa, Carlos A. Zarate
Harvard Review of Psychiatry February 21, 2018 DOI: 10.1097/hrp.0000000000000183 via OpenAlex
Summary
Glutamatergic system dysfunction is implicated in bipolar depression and major depressive disorder. Subanesthetic doses of ketamine produce rapid reductions in depressive symptoms, prompting the development of other glutamatergic modulators. This review highlights evidence for antidepressant effects of broad modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine, AVP-786, nitrous oxide, AZD6765), NR2B-specific NMDA receptor antagonists (traxoprodil, MK-0657), glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and metabotropic glutamate receptor modulators (AZD2066, basimglurant, JNJ40411813, RG1578).
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | ketamine esketamine dextromethorphan dextromethorphan-quinidine AVP-786 nitrous oxide AZD6765 traxoprodil MK-0657 D-cycloserine GLYX-13 sarcosine AV-101 AZD2066 basimglurant JNJ40411813 RG1578 |
| Keywords | Glutamatergic Dextromethorphan Pharmacology Nmda receptor Bipolar disorder |
| Citations | 94 |
| Key finding | Glutamatergic modulators, particularly ketamine, show antidepressant effects in mood disorders. |
Abstract
LEARNING OBJECTIVE: 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]).