This double-blind, randomised, controlled trial (n=183), known as the Ketamine for Adult Depression Study (KADS), explored the effectiveness of ketamine therapy in treating patients with treatment-resistant depression (TRD).
Randomised, double-blind RCT phase: subcutaneous ketamine (100 mg/mL) given twice weekly for 4 weeks; participants screened 1 month after RCT for eligibility to enter a 4-week open-label extension after a 1-month break.
Dosing is weight-based by volume (0.22–0.53 mL starting volumes depending on body weight) with the possibility of dose increases up to 0.91 mL; adherence ensured by staff-administered injections. Primary outcome: remission at end of RCT phase (MADRS <10); MADRS change also assessed.
Generic KADS ketamine arm used for papers that report combined-cohort ketamine analyses.
Subcutaneous racemic ketamine; fixed-dose cohort used 0.5 mg/kg and flexible-dose cohort escalated 0.5-0.9 mg/kg.
Generic KADS active-control arm used for papers that report combined-cohort midazolam analyses.
Subcutaneous midazolam active control; fixed-dose cohort used 0.025 mg/kg and flexible-dose cohort escalated 0.025-0.045 mg/kg.
KADS cohort 1 fixed-dose subcutaneous racemic ketamine.
Subcutaneous injection.
KADS cohort 1 fixed-dose subcutaneous midazolam active control.
Subcutaneous injection active control.
KADS cohort 2 response-guided flexible-dose subcutaneous racemic ketamine.
Subcutaneous injection; escalation steps 0.6, 0.75, and 0.9 mg/kg if not improved by 50%.
KADS cohort 2 response-guided flexible-dose subcutaneous midazolam active control.
Subcutaneous active control; escalation steps matched ketamine injection volumes.