Low-dose ketamine improved brain network integrity among patients with treatment-resistant depression and suicidal ideation.
Psychiatry research – March 01, 2025
Source: PubMed
Summary
A single low dose of ketamine shows promise in rapidly improving brain network connections while reducing depression and suicidal thoughts. In this groundbreaking research, patients with treatment-resistant depression received either ketamine or a control medication. Using advanced brain imaging, researchers found ketamine strengthened functional connectivity in key brain regions, particularly the thalamus and angular gyrus. These improvements in brain network organization corresponded with significant reductions in depressive symptoms and suicidal ideation.
Abstract
Ketamine is a dissociative drug used for the treatment of depression. However, the neurofunctional mechanism underlying the antidepressant effect of ketamine remains unknown. According to previous research, low-dose ketamine affects large-scale brain networks, including default-mode and salient networks. A total of 43 patients with treatment-resistant depression (TRD) and suicidal ideation (SI) were randomly assigned to receive a single infusion of either 0.5 mg/kg ketamine or 0.045 mg/kg midazolam. Depressive and suicidal symptoms were evaluated using the 17-item Hamilton Depression Rating Scale and the Columbia-Suicide Severity Rating Scale: Ideation Severity Subscale. Resting-state functional magnetic resonance imaging was performed at baseline and on day 3 after infusion. Graph theoretic metrics such as degree centrality and clustering coefficient were examined. Relative to midazolam use, low-dose ketamine infusion reduced depressive (p = 0.001) and suicidal (p = 0.025) symptoms and improved the brain network integrity, including increased degree centrality and clustering coefficient in the angular gyrus and increased degree centrality in the right thalamus. Neurofunctional changes in the thalamus and default-mode network (angular gyrus) may be associated with the antidepressant effect of ketamine on patients with TRD and SI. UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000033916.