The effect of glutamatergic modulators on sleep behavior and architecture in depressive disorders: A systematic review.
Journal of Psychiatric Research June 1, 2026 Kyle Valentino, Hana Ballum, William Cheung et al.
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.