A Trial to Assess the Effects of Prazosin or Propranolol on Blood Pressure in the Presence of Brexpiprazole/Sertraline

• Propranolol (Drug): Propranolol (tablet, oral ): 40 mg QD Day 3 and Day 21 Intervention 1 is a single dose of prazosin administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.
• Prazosin (Drug): Prazosin (tablet, oral): 1 mg QD Day 2 and Day 20 Intervention 2 is a single dose of propranolol administered in the presence of sertraline alone at steady state or in the presence of sertraline + brexpiprazole at steady state.

Primary outcomes

• Changes between the control and treatment periods on Day 19 vs. Day 1, Day 20 vs. Day 2, and Day 21 vs. Day 3, with prazosin or propanolol in the presence of brexpiprazole + sertraline or sertraline alone at steady state [21 days]: Mean difference in baseline-adjusted change in systolic blood pressure (ΔΔSBP), measured in mmHg, from supine to standing positions will be assessed.
• Maximum change in SBP, measured in mmHg, from supine to standing position in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. [21 days]
• Maximum change in diastolic blood pressure (DBP), measured in mmHg, from supine to standing position in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. [21 days]
• Maximum change in resting heart rate (HR), measured in beats per minute (bpm), from supine to standing position will be assessed in the presence of brexpiprazole + sertraline or sertraline alone at steady state will be assessed. [21 days]

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Primary Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition criteria Diagnosis of Major Depressive Disorder, post-traumatic stress disorder, generalized anxiety disorder, panic disorder, social anxiety disorder or obsessive-compulsive disorder
* Must be able to receive a sertraline dose of 150 mg/day by the second screening visit (Day -15)

Exclusion Criteria

* Sexually active males or females, who could become pregnant, not agreeing to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days at the end of the study
* Diagnosed hypertension (including treated or untreated hypertension), or orthostatic hypotension
* Epilepsy or a history of seizures
* History of neuroleptic malignant syndrome or serotonin syndrome.
* Primary DSM-5 diagnosis of Schizophrenia spectrum and other psychotic disorders, Bipolar and related disorders, Feeding and eating disorders (including anorexia nervosa or bulimia), Neurocognitive disorders (including but not limited to delirium, major or mild neurocognitive disorder due to Alzheimer's, Parkinson's, or traumatic brain injury)
* A significant risk of committing violent acts, serious self-harm, or suicide
* History of diabetes mellitus (type 1 or type 2)
* Subjects with any previous exposure to brexpiprazole, or subjects with chronic use of prazosin or propranolol in the 90 days prior to the screening visit or any use in the 21 days (3 weeks) prior to the screening visit.