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This study explores responses to ketamine in patients with treatment-resistant depression (TRD) using a wearable forehead electroencephalography (EEG) device. We recruited and randomly assigned 55 outpatients with TRD into three approximately equal-sized groups (A: 0.5-mg/kg ketamine; B: 0.2-mg/kg ketamine; and C: normal saline) under double-blind conditions. The ketamine responses were measured by EEG signals and Hamilton depression rating scale scores. At baseline, the responders showed significantly weaker EEG theta power than the non-responders (p &lt;; 0.05). Compared to the baseline, the responders exhibited higher EEG alpha power but lower EEG alpha asymmetry and theta cordance post-treatment (p &lt;; 0.05). Furthermore, our baseline EEG predictor classified the responders and non-responders with 81.3 &#x00B1; 9.5% accuracy, 82.1 &#x00B1; 8.6% sensitivity, and 91.9 &#x00B1; 7.4% specificity. In conclusion, the rapid antidepressant effects of mixed doses of ketamine are associated with prefrontal EEG power, asymmetry, and cordance at baseline and early post-treatment changes. Prefrontal EEG patterns at baseline may serve as indicators of ketamine effects. Our randomized double-blind placebo-controlled study provides information regarding the clinical impacts on the potential targets underlying baseline identification and early changes from the effects of ketamine in patients with TRD.

Identifying Ketamine Responses in Treatment-Resistant Depression Using a Wearable Forehead EEG