Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.
European archives of psychiatry and clinical neuroscience August 29, 2024 Florian Freudenberg, Christine Reif-Leonhard, Andreas Reif 10 citations
Changes in glutamate-related brain plasticity may underlie depression, leading researchers to explore components of the glutamate synapse as targets for faster-acting antidepressants. The NMDA receptor blocker ketamine and its S-enantiomer esketamine already show rapid antidepressant effects. This review examines other glutamatergic rapid-acting antidepressants beyond (es)ketamine that have meaningful clinical trial data, including arketamine, esmethadone, nitrous oxide, and other glutamate receptor modulators. Substances successful only in preclinical studies or case reports are discussed marginally. The authors aim to highlight glutamatergic modulation's critical role in advancing antidepressant therapy, potentially improving clinical outcomes and reducing depression's burden through faster therapeutic effects.