Oral ketamine effects on dynamics of functional network connectivity in patients treated for chronic suicidality.
Zack Y Shan, Adem T. Can, Abdalla Z Mohamed, Megan Dutton, Daniel F. Hermens, Vince D Calhoun, Leanne M Williams, Maxwell R. Bennett, Jim Lagopoulos
European Archives of Psychiatry and Clinical Neuroscience May 21, 2024 DOI: 10.1007/s00406-024-01831-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Peer reviewed |
|---|---|
| Sample size | 29 |
| Population | Patients with chronic suicidality |
| Intervention | oral ketamine |
| Duration | 6-week intervention, 10-week follow-up |
| Topics | Ketamine Esketamine |
| Keywords | Chronic suicidality Dynamic functional connectivity Neural networks FMRI Ketamine-therapy Brain-connectivity Suicide-prevention Neuroscience-research Medical-imaging |
| Citations | 3 |
| Key findings | Ketamine increased transitions among whole-brain connectivity states and increased dwelling time in a highly synchronized brain state, which correlated with reduced suicidal ideation; persistent responders had a higher baseline fraction of a cognitive control network state. |
Abstract
The underlying brain mechanisms of ketamine in treating chronic suicidality and the characteristics of patients who will benefit from ketamine treatment remain unclear. To address these gaps, we investigated temporal variations of brain functional synchronisation in patients with suicidality treated with ketamine in a 6-week open-label oral ketamine trial. The trial's primary endpoint was the Beck Scale for Suicide Ideation (BSS). Patients who experienced greater than 50% improvement in BSS scores or had a BSS score less than 6 at the post-treatment and follow-up (10 weeks) visits were considered responders and persistent responders, respectively. The reoccurring and transient connectivity pattern (termed brain state) from 29 patients (45.6 years ± 14.5, 15 females) were investigated by dynamic functional connectivity analysis of resting-state functional MRI at the baseline, post-treatment, and follow-up. Post-treatment patients showed significantly more (FDR-Q = 0.03) transitions among whole brain states than at baseline. We also observed increased dwelling time (FDR-Q = 0.04) and frequency (FDR-Q = 0.04) of highly synchronised brain state at follow-up, which were significantly correlated with BSS scores (both FDR-Q = 0.008). At baseline, persistent responders had higher fractions (FDR-Q = 0.03, Cohen's d = 1.39) of a cognitive control network state with high connectivities than non-responders. These findings suggested that ketamine enhanced brain changes among different synchronisation patterns and enabled high synchronisation patterns in the long term, providing a possible biological pathway for its suicide-prevention effects. Moreover, differences in cognitive control states at baseline may be used for precise ketamine treatment planning.
Comparable studies
Other non-randomized and open-label trials on ketamine, most cited first.
Citations in the library
Cited by 2
Cites 11
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- Side-effects associated with ketamine use in depression: a systematic review. The Lancet Psychiatry 2018
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
and 6 more in the library