Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
Condition: Major Depression
MeSH terms: Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      The goal of the proposed research is to determine the mechanism of action of an
      antidepressant of known efficacy (bupropion) and to tie this mechanism of action to a
      biomarker of inflammation in support of precision medicine for the treatment of major
      depression (MD). MD is a devastating disease affecting approximately 10% of US adults and
      being the leading cause of disability worldwide. Despite availability of several classes of
      antidepressant medications, initial treatment response is low (around 30%), and approximately
      1/3 of depressed patients are non-responsive to conventional antidepressant therapies.
      Although extensive reviews of the literature suggest that available antidepressant
      medications are equally effective, recent studies suggest that there may be differential
      responsiveness to conventional antidepressants among subgroups of depressed patients. One
      subgroup of depressed patients who may exhibit differential antidepressant responsiveness are
      those with increased markers of inflammation. Data from previous studies support the notion
      that differential responsiveness to conventional antidepressants exists and may be revealed
      by pretreatment levels of inflammation as indexed by the inflammatory biomarker C-reactive
      protein (CRP).

      This study proposes to use a mechanistic clinical trial design with drugs of known efficacy
      to take the first step toward establishing whether antidepressants that target dopamine (e.g.
      bupropion) might be a better choice for depressed patients with increased inflammation and
      anhedonia than an selective serotonin reuptake inhibitor (SSRI). Accordingly, 50 depressed
      patients with a CRP>2mg/L and increased anhedonia will be randomized to 8 weeks of bupropion
      or escitalopram in order to analyze data from 40 patients (accounting for drop outs). All
      depressed patients will undergo functional magnetic resonance imaging (fMRI) to examine
      functional connectivity in reward-related circuits at baseline and 4 and 8 weeks along with
      objective and clinical assessments of Research Domain Criteria (RDoC) positive (motivational)
      valence constructs at baseline and 2, 4, 6 and 8 weeks.

      The researchers hypothesize that patients who receive bupropion versus escitalopram will
      exhibit increased functional connectivity between ventral striatum and ventromedial
      prefrontal cortex in association with decreased motivational deficits and anhedonia.
    

Intervention name(s): Bupropion XL; Escitalopram
Intervention type(s): Drug; Drug
Intervention description(s): 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.
Other intervention name(s): Wellbutrin; Lexapro
Intervention MeSH terms: Bupropion; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Inflammation