Randomised, triple-blind, placebo-controlled, parallel-group Phase II trial (n=30) comparing single IV ketamine 0.5 mg/kg versus saline infusion in adults with treatment-resistant depression; primary outcomes include central and peripheral GABA and glutamate changes and change in MADRS at 24 hours.
Adults with treatment-resistant major depressive disorder will be randomised 1:1 to a single 40-minute IV racemic ketamine infusion (0.5 mg/kg) or normal saline in an MRI scanner; an optional open-label ketamine infusion is offered 1–7 days later.
Primary analyses relate peak central GABA and glutamate measured by sliding-window fMRS during infusion to peripheral GABA and glutamate changes by LC–MS from baseline to 24 hours, and to change in MADRS.
Single IV racemic ketamine infusion 0.5 mg/kg (max 50 mg cap for >100 kg)
40-min infusion; optional open-label ketamine 1–7 days after initial treatment; max 50 mg cap for >100 kg
Normal saline 40-min IV infusion (placebo comparator)
Normal saline 40-min infusion; participants may receive optional open-label ketamine 1–7 days later