This interventional trial, led by The George Institute, aims to compare the effectiveness of two formulations of ketamine (esketamine (Spravato®) and racemic ketamine), in treating treatment-resistant depression (TRD).
Randomised, prospective, rater-blinded (outcome assessors) parallel-group comparative effectiveness trial comparing racemic IV ketamine and intranasal esketamine (Spravato®) in people with treatment-resistant depression.
Primary outcomes include comparative effectiveness on depressive symptoms after initial treatment; secondary outcomes include acceptability, safety, quality of life, function and health-economic endpoints with follow-up from 4 weeks to 6 months. Treatments are delivered in participating ketamine clinics following clinic protocols with randomisation to one of the two modalities.
IV racemic ketamine with clinic-guided dose optimisation and titration.
Typical starting 0.5 mg/kg; titration to max 1.5 mg/kg as needed.
Intranasal esketamine dosing per Spravato® product information with clinic-guided adjustments.
Intranasal Spravato®: starting dose 28 or 56 mg (≥65 start 28 mg); options 28/56/84 mg; Weeks1–4 twice weekly, Weeks5–8 weekly, then maintenance.