Change in study design based on phase 1 data collection; patient burden was not feasible

Moderate-intensity propofol treatments will be administered to participants who are non-responders at the end of Phase 1.

Inclusion Criteria:

• Age 18-55
• Diagnosis of major depressive disorder or bipolar disorder
• Current moderate-to-severe depressive episode
• Episode duration more than 2 months and less than 5 years
• Failure of at least 2 adequate antidepressant medication trials within the past 2 years
• Body mass index < 40
• 16-item Quick Inventory of Depressive Symptomatology, self-rated > 10

Exclusion Criteria:

• Contraindication to propofol or midazolam
• Daily use of benzodiazepine, opioid, ACE inhibitor, or ARB medication
• Symptomatic coronary artery disease or heart failure
• Poorly controlled hypertension or diabetes
• Abnormal kidney or liver function
• Pregnant or breast feeding
• Traumatic brain injury or significant neurologic signs (past year)
• Substance use disorder (past year)
• Obsessive compulsive disorder (current)
• Post-traumatic stress disorder (current)
• Schizophrenia-spectrum disorder (lifetime)
• Neurocognitive disorder (current)
• Personality disorder as a current focus of treatment
• ECT within the past 3 months
• Inappropriate for ECT, or poor response to ECT within the past 5 years
• Incompetent to provide consent