In treatment-resistant depression, four intravenous ketamine infusions (0.5 mg/kg) given over 2–3 days led to significant improvements in depression and anhedonia scores. Brain scans revealed decreased neurite density in occipitotemporal white matter pathways after treatment. Greater reductions in anhedonia correlated with decreased neurite density in the left internal capsule and left superior longitudinal fasciculus. No significant changes were seen in other white matter measures. The neurite orientation dispersion and density imaging model may detect ketamine-induced white matter changes more sensitively than standard diffusion tensor imaging.
Ketamine treatment improves cognitive function in people with treatment-resistant depression, and these improvements last at least five weeks. In a study of 66 patients receiving four ketamine infusions, significant gains occurred in inhibition, working memory, processing speed, and overall fluid cognition after the first and fourth infusions. Processing speed and overall fluid cognition remained improved at a five-week follow-up, even though depressive symptoms had largely returned to baseline by then. Baseline working memory and changes in inhibition were moderately linked to antidepressant response, but cognitive improvements were statistically independent of mood changes, suggesting ketamine acts on overlapping but distinct brain systems.