People with treatment-resistant depression show higher REM density in the first REM period and shorter REM latency than healthy volunteers, while total night REM density does not differ. Ketamine treatment reduces REM density in the first REM period but does not change total night REM density or REM latency. Baseline REM density in the first REM period moderately predicts whether a person will respond to ketamine, with higher levels indicating greater likelihood of response. This marker could help identify individuals most likely to benefit from ketamine therapy.
Slow-wave activity (SWA) during early non-rapid eye movement sleep is lower in people with treatment-resistant depression (TRD) than in healthy volunteers. Ketamine, but not placebo, increases SWA in TRD patients, especially those who respond to treatment, while having no effect on SWA in healthy volunteers. Ketamine also improves overall sleep in TRD patients by increasing total sleep time and sleep efficiency and reducing sleep latency. The increase in SWA after ketamine lessens with age. The findings suggest that ketamine's antidepressant effects are closely tied to its modulation of early sleep SWA and its ability to improve sleep architecture in TRD.