Low-dose ketamine improved brain network integrity among patients with treatment-resistant depression and suicidal ideation.
Tung-Ping Su, Li-Kai Cheng, Pei-Chi Tu, Li-Fen Chen, Wei-Chen Lin, Cheng-Ta Li, Ya-Mei Bai, Shih-Jen Tsai, Mu-Hong Chen
Psychiatry Research March 1, 2025 DOI: 10.1016/j.psychres.2025.116377 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Patients with treatment-resistant depression and suicidal ideation |
| Interventions | Ketamine Midazolam |
| Dose | 0.5 mg/kg ketamine, 0.045 mg/kg midazolam |
| Duration | Single infusion, follow-up on day 3 |
| Topics | Depression Ketamine Esketamine |
| Keywords | Functional connectivity Graph theory Suicidal ideation Ketamine therapy Brain connectivity Mental health treatment Suicide prevention |
| Citations | 6 |
| Key findings | Low-dose ketamine infusion reduced depressive and suicidal symptoms and improved brain network integrity in the angular gyrus and right thalamus compared to midazolam. |
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.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.
Citations in the library
Cited by 2
- Esketamine/Ketamine: Dual‐Action Mechanisms and Clinical Prospects beyond Anesthesia in Psychiatry, Immunology, and Oncology Advanced Science December 14, 2025
- A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals? Journal of Affective Disorders April 15, 2026
Cites 9
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Investigating the Functional Heterogeneity of the Default Mode Network Using Coordinate-Based Meta-Analytic Modeling Journal of Neuroscience November 18, 2009
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
- International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators Molecular Psychiatry September 7, 2022
- Ketamine effects on default mode network activity and vigilance: A randomized, placebo‐controlled crossover simultaneous fMRI/EEG study Human Brain Mapping September 18, 2019
and 4 more in the library