Sleep dysfunction and hallucinatory experiences are bidirectionally related, with the strongest path leading from poor sleep to hallucinations. This narrative review examines mechanisms across four levels: phenomenology, psychology, neural networks, and neurophysiology. Stress is a well-supported mediator, with sleep manipulation studies in non-clinical populations showing its role. Sleep loss also affects nervous system inflammation, altering brain connectivity involved in hallucinations. Lived-experience accounts reveal three novel mechanisms—source monitoring, mental resilience, and reasoning skills—that are impacted by sleep loss, though the full causal chain requires further testing. Priorities include testing stress as a mediator in clinical populations and experimentally examining these novel mediators.
Ketamine and its enantiomers show rapid antidepressant effects for major depressive disorder and bipolar disorder, but responses vary widely. This systematic review of 26 studies (1694 participants) found that ketamine treatment is linked to improved subjective sleep quality. Preliminary evidence suggests that baseline sleep disturbances and early sleep improvements may predict antidepressant response. Some studies also indicate beneficial effects on objective sleep and circadian rhythmicity, but this finding is tentative due to few published articles. The authors call for more research on objective circadian measures and potential synergy with chronotherapies.
Ketamine and its enantiomer esketamine are effective in only 30-35% of patients with treatment-resistant depression. Increased serum brain-derived neurotrophic factor (BDNF) after a single intravenous dose has been proposed as a biomarker of antidepressant response, but effects under different treatment schedules are unclear. In a randomized, placebo-controlled trial of six-week, low-dose, oral esketamine (90 mg/day, three 30 mg intakes), depression severity and serum BDNF were measured in 54 patients at baseline, end of treatment, and after a four-week washout. BDNF levels did not significantly differ between esketamine and placebo groups during treatment or washout. An increase in BDNF occurred regardless of treatment condition.