Chronic Kidney Disease Antidepressant Sertraline Trial

This is a randomized double-blinded placebo-controlled trial of adults with predialysis
stages 3-5 Chronic Kidney Disease and Major Depressive Episode. Subjects will be randomized
in a double-blind fashion to placebo or sertraline (beginning at 50 mg/d and escalated by 50
mg increments every 2 weeks to a maximum of 200 mg/d) and followed for 12 weeks. The primary
outcome is to investigate if treatment with sertraline, as compared with placebo, results in
an improvement in depression symptom severity as measured by the Quick Inventory of
Depressive Symptomatology Clinician Rated (QIDS-C-16) score. Secondary outcomes include
whether sertraline, as compared with placebo, improves overall function and quality of life
and whether it will result in more serious adverse events.

Inclusion Criteria:

- Male or female adults aged greater than 21 years.

- Predialysis stages 3, 4 or 5 CKD.

- Current Major Depressive Episode.

- QID-C-16 score of 11.

- Able to understand and sign informed consent.

Exclusion Criteria:

- No healthcare power of attorney to sign informed consent.

- Unwilling or unable to participate.

- Kidney transplant recipient.

- Initiated on maintenance dialysis

- Significant hepatic dysfunction or liver enzyme abnormalities 3 times the upper limits
of normal.

- Terminal chronic obstructive pulmonary disease or cancer.

- Recent history of active bleeding, such as gastrointestinal bleeding requiring
hospitalization 3 months prior

- Current use of class I anti-arrhythmic medications.

- Use of pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine or methyldopa;
tri-cyclic anti-depressants, neuroleptics or anti-convulsants, excluding gabapentin

- Use of other serotonergic drugs or supplements such as triptans, tramadol, linezolid,
tryptophan, and St. John's Wort.

- Ongoing use of anti-depressants

- Past treatment failure on Sertraline

- Initiation of psychotherapy for depression in the 3 months prior to study entry

- Alcohol or substance abuse or dependence that requires acute detoxification at study
entry

- Present or past psychosis or Bipolar I or II disorder

- Dementia or a Mini-Mental State Examination score of <23

- Suicidal ideation

- Pregnancy, lactation and women of childbearing potential not using adequate
contraception