Shorter to be effective: subanesthetic-dose ketamine infusion reduces the global and regional path length of brain functional connectivity in patients with treatment-resistant depression and suicidal ideation.
Wei-Chen Lin, Li-Kai Cheng, Tung-Ping Su, Li-Fen Chen, Pei-Chi Tu, Cheng-Ta Li, Ya-Mei Bai, Shih-Jen Tsai, Mu-Hong Chen
Psychopharmacology (Berl) May 22, 2026 DOI: 10.1007/s00213-026-07089-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blinded clinical trial Peer reviewed |
|---|---|
| Sample size | 43 |
| Population | Patients with treatment-resistant depression and strong suicidal symptoms |
| Interventions | Ketamine Midazolam |
| Dose | 0.5 mg/kg ketamine; 0.045 mg/kg midazolam |
| Duration | Neuroimaging before infusion and on day 3 after infusion |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine produced a substantially lower mean global path length than midazolam after infusion, with regional path lengths decreased in the anterior cingulate cortex, posterior cingulate cortex, supplementary motor area, superior parietal lobule, and superior frontal gyrus. The authors suggest these decreases indicate improved network integration following subanesthetic-dose ketamine, and state that further studies are needed to validate the findings. |
Abstract
Background: Studies have demonstrated that subanesthetic-dose ketamine may modulate the functioning of specific depression-related brain regions, particularly the anterior cingulate cortex and prefrontal cortex. However, how subanesthetic-dose ketamine alters the global and regional graph theory metrics of resting-state functional connectivity in patients with treatment-resistant depression (TRD) and strong suicidal symptoms remains unclear.
Methods: We conducted a randomized, double-blinded, resting-state functional magnetic resonance imaging clinical trial in patients with TRD and strong suicidal symptoms. These patients received either subanesthetic-dose ketamine (0.5 mg/kg, n = 21) or midazolam (0.045 mg/kg, n = 22). Neuroimaging was performed before infusion and on day 3 after infusion. A graph theory analysis was conducted to calculate global and regional metrics after infusion.
Results: Compared with the midazolam group, the ketamine group exhibited a substantially lower mean global path length after infusion. Specifically, in patients who received subanesthetic-dose ketamine treatment, the regional path lengths were decreased in key depression-related brain regions such as the anterior cingulate cortex, posterior cingulate cortex, supplementary motor area, superior parietal lobule, and superior frontal gyrus.
Discussion: Decreased global and regional path lengths suggest improved network integration following subanesthetic-dose ketamine treatment in patients with TRD and strong suicidal symptoms. Further studies are required to validate our findings.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.