Warners Bay

Researchers are comparing two forms of ketamine—Spravato® and racemic ketamine—to see how well they work for people with treatment-resistant depression (TRD). The study aims to understand their effectiveness, patient acceptance, safety, impact on quality of life and function, and cost effectiveness. This phase 4 trial involves people with TRD who have not responded to at least two different antidepressants and are currently experiencing a depressive episode. Participants will be randomly assigned to receive either Spravato® or racemic ketamine. Spravato® dosing starts with 56 mg for those under 65 and 28 mg for those 65 and older, with subsequent doses given twice weekly for 4 weeks, then weekly or every two weeks. Racemic ketamine dosing begins at 0.5 mg/kg and may be increased stepwise up to 1.5 mg/kg based on response. Treatments are provided as part of usual clinical care alongside research assessments. During the study, participants will complete questionnaires about mood, treatment acceptability, side effects, quality of life, function, and economic outcomes. The primary outcome is measured by the Montgomery-Asberg Depression Rating Scale (MADRS) over 4 weeks. Participants are followed for 4 weeks to 6 months, with treatment and assessments integrated into their clinical care settings.