Combination of Novel Therapies for CKD Comorbid Depression

Inclusion Criteria: 1. Male or female adults aged 18 years or greater. There will be no upper age limit. 2. Presence of CKD stages 3b, 4 or 5, with an estimated glomerular filtration rate (GFR) of \<45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula. 3. Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria 4. Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization. 5. Able to understand and sign informed consent after the nature of the study has been fully explained 6. Kidney transplant patients that are at least 6 month post-transplantation (3 months post-transplant, with at least another 3 months to confirm eGFR \<45) Exclusion Criteria: 1. Unable to understand or give informed consent. 2. Unwilling or unable to participate in the protocol or comply with any of its components 3. Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal 4. Terminal chronic obstructive pulmonary disease or cancer 5. Presence of seizure disorder 6. Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants 7. Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort. 8. Use of medications known to cause QT prolongation on EKG 9. Ongoing use of antidepressant medications for depression treatment 10. Past treatment failure on bupropion 11. Initiation of depression-focused psychotherapy in the 3 months prior to study entry 12. Active alcohol or substance abuse or dependence that requires acute detoxification at study entry 13. Present or past psychosis or Bipolar I or II disorder 14. Dementia or a Mini-Mental State Examination score \<23 15. Active suicidal intent 16. Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception