Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt - Goethe University Frankfurt, Frankfurt am Main, Germany.
2 papers in the library · 13 citations · publishing 2024-2025
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.
Repeated intravenous esketamine infusions improved emotion recognition for all emotions except sadness, where accuracy decreased, particularly for low-intensity expressions. Misclassifications of other emotions as sad also decreased, indicating a reduced response bias towards sadness. This shift emerged after the first infusion and consolidated over time. Participants showed significant reductions in feelings of sadness and irritability, and cognitive functioning improved. Among those receiving at least five infusions, 66.7% showed significant improvement. The findings suggest that esketamine's antidepressant effects may involve changes in emotion processing and cognition, with acute mood-lifting effects distinguishable from longer-lasting responses that consolidate after repeated administration.