Ketamine Biomarker Validation

This Phase I, randomised, triple-masked, parallel trial (n=20) will study EEG biomarker development for ketamine infusion in adults with treatment-resistant depression and will assess the effects of three ketamine doses on depressive symptoms and EEG signals, with the Hamilton Depression Rating Scale (HDRS-22) measured through 72 hours as a primary outcome. Participants aged 18–59 who meet DSM-5 criteria for a major depressive episode in the context of major depressive disorder and who score ≥22 on the Montgomery-Åsberg Depression Rating Scale (stable antidepressant dose for ≥6 weeks permitted) will be randomised to one of three ketamine infusion arms: 0.25 mg/kg, 0.5 mg/kg or 0.75 mg/kg. EEG recordings and HDRS-22 will be collected at baseline, Hour 1, Hour 4, Hour 24 and Hour 72 post-infusion; key exclusions include lifetime bipolar or psychotic disorders, recent ECT, IV drug use, prior nonresponse or intolerance to ketamine, pregnancy or inadequate contraception, active suicidality, and concurrent use of antipsychotics or other medicines likely to interact with GABA or glutamate. Sponsor: Soterix Medical; planned start 2025-12-20, completion 2028-03-01.