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.
In patients with treatment-resistant depression and strong suicidal thoughts, a single low-dose infusion of ketamine did not change blood levels of two proteins—VEGF and MMP-9—compared to a control drug, midazolam. However, patients who had higher VEGF levels before treatment showed greater improvements in depression and suicidal ideation after ketamine. This suggests that baseline VEGF might help predict who will benefit from ketamine, but the drug itself does not alter these protein levels.
A single low-dose ketamine infusion (0.5 mg/kg) compared to a low-dose midazolam control (0.045 mg/kg) resulted in higher serum levels of the anti-aging hormone klotho three days after treatment in 48 patients with treatment-resistant depression and strong suicidal ideation. However, ketamine did not significantly increase klotho levels from baseline, and changes in klotho were not associated with changes in depressive or suicidal symptoms. Higher baseline klotho levels predicted a poorer antidepressant response to ketamine. The findings suggest klotho may be involved in ketamine's antidepressant mechanism, but further molecular studies are needed.