Bupropion for Depression in ESRD Patients on Hemodialysis
Condition: Major Depression; End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic; Depression; Depressive Disorder
Intervention: Fluoxetine; Bupropion
Intervention description: Antidepressant; Antidepressant
Intervention MeSH terms: Bupropion; Fluoxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: depression; ESRD; hemodialysis

Summary:

      The proposed study will evaluate the response and remission rates for major depressive
      disorder (MDD) in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis
      (HD) treated with bupropion or fluoxetine for 12 weeks. In addition, the study will document
      the relative tolerability and safety, and longitudinally contrast the effects of bupropion
      and fluoxetine on measures of cognitive function, fatigue, inflammation, and tryptophan (TRP)
      and TRP catabolites in blood. It is hypothesized that both drugs will significantly reduce
      MDD symptoms from baseline, and be tolerable and safe, but bupropion will be associated with
      greater reduction in pro-inflammatory cytokines, cognitive impairment, and fatigue compared
      with fluoxetine.

      The Specific Aims of this study are:

      Aim 1: Determine the efficacy of bupropion and fluoxetine in treatment of MDD in ESRD/HD
      patients.

      Aim 2: Determine whether longitudinal change in MDD symptoms, cognitive dysfunction, and
      fatigue differ between bupropion and fluoxetine.

      Aim 3: Determine whether longitudinal change in MDD symptoms, cognitive dysfunction, and
      fatigue correlate with change in inflammation, measures of TRP availability to brain, or
      neurotoxic TRP metabolites.

      Hypotheses:

        1. Bupropion and fluoxetine will both show efficacy in treating MDD;

        2. Bupropion will lead to greater improvement in cognitive dysfunction and fatigue than
           fluoxetine; and

        3. Change in cognition and fatigue over time will correlate with change in c-reactive
           protein (CRP) and quinolinic acid and change in overall depression score will correlate
           with measures of TRP availability.
    

Eligibility criteria:

        Inclusion Criteria:

          -  age 30-70 yrs;

          -  have patent and non-infected arteriovenous fistula or graft;

          -  are receiving maintenance HD 3 times per week lasting for 3-4 hours;

          -  serum albumin of ≥ 3.2 g/dl, serum phosphate of <6.5 mg/dl, and serum hemoglobin of ≥9
             mg/dl in consecutive two blood tests as per the National Kidney Foundation Disease
             Outcomes Quality Initiative (NKF KDOQI) guidelines [subjects failing screening due to
             blood test will be allowed to be re-screened in 30 days];

          -  receiving stable or maintenance dose of iron or erythropoietin-stimulating agents,
             statins, angiotension receptor blockers and/or angiotension converting enzyme
             inhibitors, phosphate binders, vitamin D receptor analogs as these agents may
             influence cytokines proposed in the study;

          -  meet the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)
             criteria for MDD;

          -  have a Ham-D score > 17

        Exclusion Criteria:

          -  meet DSM-IV criteria for Bipolar Disorder or other psychotic disorder in the month
             prior to screening;

          -  are taking antidepressants, anti-anxiety medications, or hypnotics (including Zyban
             for smoking cessation);

          -  having failed to respond to or tolerate bupropion or fluoxetine in the past

          -  allergic to fluoxetine or bupropion

          -  known history of HIV/AIDS; No testing will be conducted for screening purposes

          -  known history of alcohol or drug abuse or dependence within the month prior to
             screening based on clinical records;

          -  history of myocardial infarction or heart failure within one month of screening or a
             history of seizures or stroke at any point;

          -  history of chronic liver disease and diagnosis of hepatic encephalopathy based on
             clinical records;

          -  currently diagnosed with cancer or receiving any cancer treatment;

          -  history of any infection within the last 2 weeks ;

          -  currently taking any antibiotics, anti-inflammatory, and immune-modulator agents;

          -  recorded noncompliance with dialysis schedules; and

          -  currently participating in clinical or behavioral intervention studies.

          -  recorded noncompliance with dialysis schedules; and

          -  currently participating in clinical or behavioral intervention studies