Ketamine and esketamine produce rapid antidepressant effects in major depressive disorder and treatment-resistant depression, but their impact on patient-reported quality of life has been unclear. A systematic review of five studies found that both agents improve quality of life measures on scales such as the WHOQOL-BREF, Assessment of Quality of Life 8D, and EuroQol-5 Dimension-5 Layers, with statistically significant results. However, the studies had an overall moderate risk of bias and varied in the quality-of-life scales used and study duration. Further research should examine effects on specific quality-of-life domains.
Sigma-1 receptors (S1Rs) may be a target and mediator of antidepressant activity. They regulate neurotransmitter release (including monoamines and glutamate), influence intracellular calcium levels, and affect immune inflammatory responses. In August 2022, the FDA approved dextromethorphan-bupropion, the first antidepressant whose hypothesized mechanism includes activity at S1Rs. The review synthesizes preclinical and clinical data on S1R physiology, pathophysiology, and function. Modulating sigma-1 systems is relevant to current FDA-approved treatments for major depressive disorder and may inform future therapeutic development. Whether sigma-1 modulation uniquely targets difficult-to-treat symptoms like anhedonia remains unknown.
About 80% of people with major depressive disorder (MDD) report insomnia. This systematic review examined how glutamatergic modulators, especially ketamine, affect sleep in preclinical and clinical studies. Preclinical work showed ketamine alters EEG delta power during NREM sleep and normalizes clock suppressor gene expression, while esketamine enhances delta power but arketamine does not. mGlu2/3 activators reduce REM sleep. Clinical studies indicate that improved sleep can mediate ketamine's antidepressant effects in MDD. The authors suggest that sleep-related mechanisms are potential targets for depression treatment.