A single infusion of the NMDA receptor antagonist ketamine rapidly reduces depressive symptoms in patients with treatment-resistant major depressive disorder. In 30 patients, ketamine increased electroencephalogram slow wave activity during early non-REM sleep and raised plasma levels of brain-derived neurotrophic factor. The occurrence of high amplitude slow waves and their slope also increased, indicating enhanced synaptic strength. Changes in BDNF levels correlated with changes in EEG parameters, but only in patients who responded to ketamine. This suggests that enhanced synaptic plasticity, reflected by increased slow wave activity and BDNF, is part of the mechanism behind ketamine's rapid antidepressant effects.
Adding mindfulness, music, and a light-occluding eye mask during ketamine infusion for depression did not improve antidepressant effects compared to ketamine alone, but it enriched the subjective experience. Participants in the combined sensory intervention group reported deeper engagement, a stronger sense of connection to reality, increased focus, moments of relief from sadness, and feelings of awe and spiritual insight. However, four individuals in that group reported discomfort. The findings suggest that while the sensory interventions make the experience more meaningful for many, they may cause discomfort for a few, and making them optional could avoid this.