Metabolic Profiling of Esketamine Treatment in Depressive Disorder

This study is examining how esketamine — a fast-acting antidepressant given as a nasal spray — changes the body's metabolism in people with treatment-resistant depression, to better understand how and why it works. Healthy volunteers will also participate for comparison. **You may be eligible if...** - For patients: you are 18–70 years old with depression that has not improved with at least two antidepressants at adequate doses - For healthy volunteers: you are 18–70 years old with no psychiatric medications **You may NOT be eligible if...** - You currently use tryptophan, St. John's Wort, or opioid pain medications - You take benzodiazepines daily - You have a psychotic disorder, substance addiction, seizures, eating disorder, dementia, epilepsy, or significant cognitive disability - You have poorly controlled high blood pressure, diabetes, or thyroid disease - You are following a weight-loss diet or taking weight-loss medications - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.