The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.
Randomized, quadruple-blind, Bayesian adaptive parallel-group design in veterans with late-life treatment-resistant depression (actual N=33) comparing single 40‑minute IV infusions of ketamine 0.10, 0.25, 0.50 mg/kg and midazolam 0.03 mg/kg.
Primary outcome is MADRS response (≥50% improvement) at 7 days; adaptive randomization aims to identify the best-performing ketamine dose. Durability assessed to 4 weeks; safety/tolerability monitored acutely and during follow-up.
Exploratory measures include neurocognitive testing, peripheral biomarkers of plasticity/inflammation, and resting-state quantitative EEG.
Single 40 min IV infusion of ketamine 0.10 mg/kg
40 min infusion
Single 40 min IV infusion of ketamine 0.25 mg/kg
40 min infusion
Single 40 min IV infusion of ketamine 0.50 mg/kg
40 min infusion
Single 40 min IV infusion of midazolam 0.03 mg/kg (active placebo)
Midazolam 0.03 mg/kg, active comparator; 40 min infusion