Double-blind, randomised, parallel-group RCT (n=24 adolescents) comparing six 0.5 mg/kg IV ketamine infusions (2/week for 3 weeks) versus six midazolam infusions; primary outcome CDRS at Day 18; 6-month open extension offers ketamine to midazolam non-responders.
Phase 1 is a 3-week double-blind parallel trial comparing six ketamine infusions (0.5 mg/kg over 40 minutes) with six midazolam infusions in 24 adolescents with treatment-resistant major depressive disorder; primary endpoint is CDRS at Day 18.
Phase 2 is a 6-month open extension offering ketamine (six infusions over 3 weeks) to midazolam non-responders; all participants are followed weekly for 6 months with monthly neurocognitive assessments and monitoring for time to relapse and safety outcomes.
IV ketamine infusions (0.5 mg/kg) given twice weekly for 3 weeks (6 infusions).
0.5 mg/kg IV infusion over 40 minutes; max single dose 40 mg (≈80 kg).
Active control midazolam infusions to maintain blinding.
Midazolam 0.045 mg/kg (max 3.6 mg per infusion) IV; used as active control.