A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression {ASCEND}

BACKGROUND Patients with end-stage renal disease undergoing maintenance hemodialysis (HD)
have to adjust to complex treatment regimens, and experience frequent care transitions. This
is compounded by a four-fold higher prevalence of comorbid depression than in the general
population, which is strongly associated with poor patient-centered outcomes. Yet, depression
is often not diagnosed when present, not treated when identified, and many HD patients are
reluctant to accept treatment. This is likely a result of lack of high-quality evidence for
the efficacy of different treatment options for comorbid depression in HD patients.
OBJECTIVES Conduct an open-label, randomized controlled clinical trial among HD patients with
comorbid depression to (1) compare the efficacy of an engagement interview with usual care in
increasing acceptability of treatment (n=200); and (2) compare the efficacy of 12 weeks of
cognitive behavioral therapy (CBT) or anti-depressant drug therapy (sertraline) for reducing
the severity of depressive symptoms, and other meaningful outcomes (n=120). METHODS HD
patients in up to 50 dialysis facilities in three different regions (Albuquerque, NM; Dallas,
TX; Seattle, WA) will be pre-screened for the presence of clinically significant depressive
symptoms. Patients with a confirmed diagnosis of major depression or dysthymia will be
randomly assigned to an engagement interview or usual care to determine efficacy in
increasing acceptability of treatment (n=200). Individuals who agree to treatment will be
randomly assigned to individual CBT or drug therapy. CBT will be administered in a dialysis
facility by a trained therapist. Sertraline will be titrated to the maximum tolerated dose
using Measurement Based Care, a model of shared-decision-making. Patient-reported outcomes
will be measured by a single assessor for all three sites, blinded to the treatment
assignment. The primary efficacy measure will be a change in severity of depressive symptoms;
secondary outcome measures will assess other important patient-reported outcomes such as
somatic symptom burden, functioning, and adherence with dialysis treatment, diet, and
medications. The longitudinal evolution of symptoms in patients who refuse to accept any
treatment either within or outside the clinical trial will also be studied (n=40). PATIENT
OUTCOMES (PROJECTED) This study will provide answers to three questions faced by HD patients
with clinically significant depressive symptoms: (1) "Given my preferences, what should I
expect will happen to me?"; (2) "What are my options, and what are the potential benefits and
harms of these options?"; and (3) "What can I do to improve the outcomes that are most
important to me?" Oversight of study will be provided by separate Patient Council and
Stakeholder Council to align with PCORI's mission of generating high-integrity,
evidence-based information from research guided by patients, caregivers, and broader health
care community.

Inclusion Criteria:

1. Age ≥ 21 years;

2. Undergoing thrice-weekly maintenance HD for ≥ 3 months;

3. Able to speak either English or Spanish;

4. BDI-II score ≥ 15; and

5. Meets diagnostic criteria for either current major depressive episode or dysthymia on
the MINI.

Exclusion Criteria:

1. Active suicidal intent;

2. Ongoing psychotherapy or current treatment with certain anti-depressant drugs;

3. Evidence of cognitive impairment on Mini-Cog;

4. Present or past psychosis or bipolar disorder I or II on the MINI;

5. Alcohol or substance abuse diagnosed on the MINI or history of such abuse in the past
three months;

6. Life expectancy < 3 months, in the judgment of the site principal investigator;

7. Anticipated to receive living related donor kidney transplantation within 3 months;

8. Pregnancy, or lactation, or women of childbearing age not willing to use adequate
birth control;

9. Clinical and/or laboratory evidence of chronic liver disease;

10. History of significant active bleeding in the past three months, such as
hospitalization for gastrointestinal bleeding;

11. Current use of class I anti-arrhythmic medications (e.g., propafenone, flecainide),
pimozide, monoamine oxidase inhibitors, reserpine, guanethidine, cimetidine,
tri-cyclic anti-depressants, triptans, tramadol, linezolid, tryptophan, and St. John's
wort; and

12. Known hypersensitivity to sertraline.