A single low-dose infusion of ketamine (0.5 mg/kg) reduced depressive and suicidal symptoms more than a low-dose midazolam infusion in 43 patients with treatment-resistant depression and suicidal ideation. Brain scans showed that ketamine increased network integrity, specifically degree centrality and clustering coefficient in the angular gyrus and degree centrality in the right thalamus. These changes in the thalamus and default-mode network may underlie ketamine's antidepressant effect.
Dysfunction in the default mode, salience, and frontoparietal networks—the triple network model—may underlie treatment-resistant depression. Analyzing resting-state functional connectivity MRI data from two clinical trials, researchers found that a single low-dose ketamine infusion altered network properties. In one trial, ketamine changed degree centrality and cluster coefficient in the right posterior cingulate cortex (default mode network) and cluster coefficient in the right supramarginal gyrus (salience network), compared to saline. In another trial, ketamine altered characteristic path length in the left posterior cingulate cortex (default mode network) compared to midazolam. A time effect on cluster coefficient in the right dorsolateral prefrontal cortex (frontoparietal network) appeared for both ketamine and saline. These findings suggest the triple-network model helps explain ketamine's antidepressant effects.
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.