Bupropion for Depression in ESRD Patients on Hemodialysis

Phase 4

Terminated

Conditions: Major Depression
End Stage Renal Disease

Interventions: Drug: Fluoxetine
Drug: Bupropion

Registration Number: NCT02238977

Lead Sponsor: University of Arkansas

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluoxetine	Fluoxetine	Fluoxetine up to 20 mg orally daily for 12 weeks. Flexible dosing between a minimum of 10 mg daily and 20 mg daily as tolerated.
Bupropion	Bupropion	Bupropion sustained release (SR) 150 mg orally twice per week

Primary Outcome Measures

Name	Time	Method
Depression Severity	up to 12 weeks	Depression severity as measured by the 25-item Hamilton Depression Rating Scale. The Hamilton Depression Rating Scale has proven useful for determining the level of depression before, during, and after treatment. It is based on the clinician's interview with the patient/participant and probes symptoms such as depressed mood, guilty feelings, suicide, sleep disturbances, anxiety levels and weight loss. The rater enters a number for each symptom construct that ranges from 0 (not present) to 4 (extreme symptoms). The higher the total score the more severe the depression. The scale is scored by summing the total of all items. The maximum possible total score is 66 and the minimum is 0. A score \> 17 is considered compatible with a diagnosis of major depression. A score \< 10 is considered clinical remission. The interview and scoring takes about 15 minutes.

Secondary Outcome Measures