Warners Bay

Researchers are evaluating and comparing two forms of ketamineSpravato4 and racemic ketaminein adults with treatment-resistant depression TRD who have not responded adequately to at least two different antidepressants. This trial aims to understand how these treatments differ in effectiveness, patient acceptance, safety, impact on quality of life and function, and overall cost effectiveness. The study is a randomized, rater-blinded, parallel group trial conducted over 4 weeks to 6 months. Participants will be randomly assigned to receive either Spravato4 nasal spray or racemic ketamine injections. Spravato4 dosing starts at 28 or 56 mg twice weekly for 4 weeks, then weekly for weeks 5-8, followed by weekly or biweekly dosing as maintenance. Racemic ketamine dosing begins at 0.5 mgkg with possible dose increases up to 1.5 mgkg, given twice weekly for 4 weeks and adjusted thereafter by the treating psychiatrist based on response and tolerability. Treatment follows standard clinical practice in the clinics providing these therapies. During the study, participants will complete questionnaires assessing mood, treatment acceptability, side effects, quality of life, function, and health economic outcomes. Multiple assessments will occur from baseline through 6 months, including depression severity scales, global impression ratings, suicide risk, cognitive function, and treatment preference. Safety monitoring and dose adjustments are guided by psychiatrists throughout the treatment period. The primary outcome is depression severity measured over the first 4 weeks.