A single low-dose ketamine infusion (0.5 mg/kg) produces an antidepressant effect lasting up to 14 days in outpatients with treatment-resistant depression and prominent suicidal thoughts, compared with a low-dose midazolam control. The antisuicidal effect, however, persists only 5 days. The benefits are most pronounced in patients whose current depressive episode has lasted less than 24 months or who have failed four or fewer prior antidepressants. The treatment is safe and well tolerated.
Ketamine infusion alters brain activity patterns in people with treatment-resistant depression, specifically in regions involved in sensory-cognitive integration, mood regulation, and cognitive control. In a study of 45 patients, those receiving ketamine showed changes in the timing and shape of hemodynamic responses in the bilateral olfactory cortex and right inferior parietal gyrus, compared to those receiving midazolam. Improvements in suicidal thoughts were linked to changes in the thalamus and superior frontal gyrus. Ketamine responders also had reduced time-to-peak in the left precuneus. These findings suggest ketamine's effects on suicidal ideation may involve neurovascular coupling dynamics.