This randomised, double-blind, midazolam-controlled, multicentre trial (n=98) will investigate the efficacy and safety of low-dose subcutaneous ketamine in adults with bipolar depression.
Parallel-group, randomised, double-blind Phase III RCT comparing twice-weekly subcutaneous ketamine (starting 0.6 mg/kg, titratable up to predefined level 4) versus low-dose subcutaneous midazolam (active placebo) over a 3-week treatment phase (maximum 6 treatments).
Primary outcome is binary remission of depression at Day 19 post-treatment commencement assessed by MADRS; tolerability and safety measured via KSET, BPRS and CADSS-6; an optional 3-week open-label extension allows additional twice-weekly ketamine for participants who continue.
Low-dose subcutaneous ketamine, titratable across predefined levels (0–4).
Subcutaneous injection; starting Level 1 = 0.6 mg/kg; titration increments 0.25 mg/kg (L1→L3) and 0.2 mg/kg (L3→L4); minimum tolerated dose 0.5 mg/kg.
Low-dose subcutaneous midazolam as active placebo, titratable across same levels during RCT phase.
Active placebo midazolam (subcutaneous); starting 0.025 mg/kg (L1); titration increments 0.0075 mg/kg (L1→L3) and 0.010 mg/kg (L3→L4).