Randomised, parallel RCT (n=62) in Veterans with treatment‑resistant depression comparing six IV ketamine infusions (0.5 mg/kg) over 12 days versus a single IV ketamine infusion (0.5 mg/kg) preceded by five midazolam infusions (0.045 mg/kg) as an active comparator.
This single‑centre, randomised, triple‑masked trial tested whether six serial IV ketamine infusions (0.5 mg/kg) are superior to a single ketamine infusion preceded by five midazolam infusions (0.045 mg/kg) for reducing depressive symptoms in Veterans with treatment‑resistant depression.
Primary outcome was MADRS score 24 hours after the last infusion. Infusions were delivered Monday‑Wednesday‑Friday over a 12‑day infusion phase; follow‑up visits occurred weekly for 4 weeks, then fortnightly for 8 weeks, then monthly until 24 weeks or relapse.
Six IV ketamine infusions (0.5 mg/kg) over two weeks (M-W-F schedule).
Infusions on days 1,3,5,8,10,12; each infusion over 40 minutes.
Single IV ketamine infusion (0.5 mg/kg) preceded by five midazolam infusions (0.045 mg/kg) as active comparator; same schedule.
Single ketamine infusion administered on final infusion day; infusion over 40 minutes.
Midazolam 0.045 mg/kg given on days 1,3,5,8,10 as active comparator.