Ketamine treatment for chronic suicidality alters how brain networks synchronize and transition over time. In a 6-week open-label trial with 29 patients, those who received ketamine showed significantly more transitions among whole-brain connectivity states after treatment. At a 10-week follow-up, patients spent more time in and more frequently visited a highly synchronized brain state, and these changes correlated with reduced suicidal ideation scores. Patients who persistently responded to ketamine had a higher baseline fraction of a cognitive control network state with strong connections, suggesting that pre-treatment brain connectivity patterns may help predict who will benefit from ketamine therapy. These findings point to a biological mechanism for ketamine's suicide-prevention effects.
Subanesthetic doses of ketamine show promise for treating suicidality, but predictive biomarkers are lacking. This study examined EEG-derived complexity measures—Lempel-Ziv complexity (LZC) and multiscale entropy (MSE)—in 31 participants receiving six weekly oral doses of racemic ketamine (0.5-3 mg/kg). Responders, defined by a ≥50% reduction in Beck Suicide Scale score or a score ≤6, showed elevated baseline eyes-open complexity compared to nonresponders, which decreased from baseline to post-treatment. Elevated baseline eyes-open LZC in responders was localized to the left frontal lobe. EEG complexity metrics may serve as sensitive biomarkers for predicting and evaluating oral ketamine treatment response.