Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
Condition: Major Depression
MeSH terms: Depression; Depressive Disorder, Major
Intervention: Bupropion XL; Escitalopram
Intervention description: Participants will take 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose will be increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.; Participants will take 10mg/d of escitalopram for two weeks, then the dose will be increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.
Intervention MeSH terms: Bupropion; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 18.0
Sex: All
Minimum age: 25 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Inflammation

Summary:

      This study is designed to determine whether bupropion (vs escitalopram) increases functional
      connectivity (FC) within reward-related neurocircuits and decreases motivational deficits in
      depressed patients with increased inflammation and anhedonia. Participants will be randomized
      to take bupropion extended release (XL) or escitalopram for 8 weeks.
    

Eligibility criteria:

        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