Randomised, parallel Phase III trial (n=140) of low-dose subcutaneous ketamine (starting 0.6 mg/kg, titrated up to 0.9 mg/kg; weekly ×4) versus low-dose midazolam in 16–25-year-olds with moderate-to-severe major depressive disorder.
Randomised, parallel, blinded Phase III study comparing weekly subcutaneous ketamine to low-dose midazolam in young people (16–25 years) with moderate-to-severe major depressive disorder; total sample size 140.
Intervention: ketamine starting at 0.6 mg/kg subcutaneously once weekly for four weeks with escalation to 0.9 mg/kg for inadequate response and reduction to 0.5 mg/kg for intolerance; comparator: midazolam 0.03 mg/kg with analogous titration (max 0.045 mg/kg, min 0.025 mg/kg). Acute observation: 4 hours after first dosing and 2 hours after subsequent doses.
Primary outcome is change in MADRS at 4 weeks versus baseline; additional follow-ups at Week 8 (Day 56) and Week 26 (Day 182) assess sustained change.
Low-dose subcutaneous ketamine with dose escalation for inadequate response and dose reduction for intolerance.
Subcutaneous injection; starting 0.6 mg/kg, escalation up to 0.9 mg/kg for inadequate response; reduction down to 0.5 mg/kg if not tolerated; initial observation 4 h, subsequent 2 h.
Low-dose subcutaneous midazolam active comparator with titration rules matching ketamine schedule.
Subcutaneous injection; starting 0.03 mg/kg, escalation to 0.045 mg/kg for inadequate response, reduction to 0.025 mg/kg if not tolerated.