Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

Inclusion Criteria

• willing and able to give written informed consent
• a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) MD, current as diagnosed by the Structured Clinical Interview for DSM-V Axis I Disorders (SCID-V)
• score of ≥16 on the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)
• off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine); concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments
• CRP>2mg/L
• Inventory of Depressive Symptomatology (IDS-SR) anhedonia subscale score ≥5

Exclusion Criteria

• history of any autoimmune disorder
• history of hepatitis B or C infection or human immunodeficiency virus infection
• history of any type of cancer requiring treatment with more than minor surgery
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing)
• history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by SCID)
• an active eating disorder or antisocial personality disorder
• a history of a cognitive disorder or ≤28 on the Mini-Mental State Exam unless otherwise approved by the PI
• pregnancy or lactation
• chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications
• use of NSAIDS or oral glucocorticoids at any time during the study
• any contraindication for MRI scanning
• failure of more than 2 antidepressant trials in the current episode
• Intolerance of bupropion or escitalopram
• BMI >40 (to exclude severe obesity)
• due to the high co-morbidity between anxiety disorders and depression, the study team plans to include patients with anxiety-related disorders excluding obsessive-compulsive disorder (OCD) if depression is the primary diagnosis. Patients with stable medical conditions and on medications for those conditions will not be excluded. Concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments.
• sexually active participants are required to use medically approved birth control methods as defined in the Birth Control Method Form for the duration of the study