The purpose of this clinical research study is to understand how effective and safe an investigational study drug called lumateperone is and whether it works to reduce the severity of depressive symptoms in adults with Major Depressive Disorder (MDD) and early life trauma. The main questions it aims to answer are:
Aim 1: To assess the efficacy of lumateperone 42 mg administered once daily compared with placebo in the treatment of patients with Major Depressive Disorder and early life abuse.
Aim 2: To assess neurocircuitry encoding of threat and reward learning as predictors of lumateperone response and as mechanisms of treatment action, and assess the change from pre-dose to post-dose of task-evoked brain activation.
Provide written informed consent before the initiation of any study-specific procedures.
Male or female, between the ages of 21 and 70 years, inclusive;
Meets the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria for Major Depressive Disorder (MDD) without psychotic symptoms, as confirmed by a trained rater using the modified Structured Clinical Interview (DIAMOND) for DSM-5,
MADRS total score ≥ 22 at Screening (Visit 1) and Baseline (Visit 2)
Has a current primary DSM-5-TR psychiatric diagnosis other than Major depressive disorder. These include: PTSD, OCD, Bipolar Disorder, Schizophrenia, schizoaffective disorder, or other psychotic disorder. Intellectual disability, Dementia or other cognitive disorders. Moderate or severe substance use disorder (excluding for nicotine)
In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during the course of his/her participation in the study or