This study is being done to learn whether lumateperone may help reduce symptoms of major depressive disorder in adults with a history of early life trauma. Researchers will also use MRI scans to study changes in brain activity during treatment.

You may be eligible for this study if you meet the following criteria.

Inclusion Criteria:

• Ages 18-70
• Diagnosed with major depressive disorder and have not seen improvement with current medication
• Willing to continue using antidepressants for the 8 weeks of the study
• Experienced trauma before the age of 16 years old
• Currently taking antidepressants and have been using them for at least 6 weeks
• Willing to try lumateperone (an antipsychotic medication) for the study
• Live in Texas
• No psychiatric conditions other than major depressive disorder
• No psychotic symptoms (e.g., hallucinations, delusions)
• Able to undergo an MRI (no permanent metal in the body)
• If applicable, willing to use a medically accepted form of birth control through the study’s duration
• Have never participated in a previous clinical trial that used lumateperone (an antipsychotic)

• Currently taking antidepressants without improvement and are willing to continue taking them during the study

• Screening: You will complete health and mental health assessments, provide blood and urine samples, and have an MRI scan to determine if you are eligible.
• Treatment: If eligible, you will take lumateperone once a day for 6 weeks while continuing your current stable antidepressant dose.
• Surveys: You will complete brief surveys on your mobile device twice a day throughout the study.
• Follow-up: After the 6-week treatment period, you will return for a safety follow-up visit and another MRI scan.
• All study visits take place in person at the Health Discovery Building in the Austin, Texas area. The study lasts about 8 weeks.

You will receive a $50 stipend for each completed study visit. You can receive an additional $50 for your 2nd and 8th visit if you complete the MRI procedures scheduled for those visits. You will also receive $2 for each completed mobile survey. Stipends are provided through Tango Cards, which can be redeemed for a variety of gift cards or charitable donations.

There is no cost for you to participate in our research study.