This study explores two treatments for treatment-resistant depression (TRD). TRD is when a person with major depression doesn't get better after trying at least two antidepressants. The study looks at *ketamine*, given through an IV (a drip into the arm), and *esketamine* (Spravato®), a nasal spray. Ketamine is not approved by the FDA for TRD, but esketamine is. The study compares how well each treatment works, how comfortable people are using them, and how well they handle any side effects.
To join, you must be 18 or older with TRD. Women who can have babies need to use effective birth control. If you have certain health problems like bipolar disorder, recent substance use issues, or specific heart conditions, you cannot join. The study will last 5 years and involve 400 participants.
- Participants will be randomly assigned to either ketamine or esketamine groups.
- You must have someone drive you home after each treatment.
- Pregnant or breastfeeding women cannot participate.