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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 |
| Topics | Depression |
| Keywords | Glutamatergic Dextromethorphan Pharmacology Nmda receptor Bipolar disorder Antidepressant Metabotropic glutamate receptor Hippocampus Cognition |
| Citations | 94 |
| Key findings | 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]).
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cited by 13
- Molecular Pharmacology and Neurobiology of Rapid-Acting Antidepressants The Annual Review of Pharmacology and Toxicology October 9, 2018
- Understanding the Mechanisms of Action and Effects of Drugs of Abuse. Molecules June 24, 2023
- Demystifying the Antidepressant Mechanism of Action of Stinels, a Novel Class of Neuroplastogens: Positive Allosteric Modulators of the NMDA Receptor. Pharmaceuticals January 24, 2025
- The role of dissociation in ketamine's antidepressant effects. Nature Communications December 22, 2020
- Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study Journal of Behavioral and Brain Science 2023
and 8 more in the library
Cites 31
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Ketamine use: a review Addiction July 21, 2011
- Ketamine Anesthesia & Analgesia November 1, 1998
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
and 26 more in the library