Sertraline, CBT Ease Depression in Patients on Dialysis

Troy Brown, RN

February 27, 2019

Cognitive-behavioral therapy (CBT) and the selective serotonin reuptake inhibitor sertraline (Zoloft, Pfizer) are each effective at easing depression among patients undergoing maintenance hemodialysis for end-stage renal disease (ESRD), a randomized trial shows.

The study, by Rajnish Mehrotra, MD, a professor of medicine (nephrology) at the University of Washington, Seattle, and colleagues, was published online February 25 in Annals of Internal Medicine.

"Sertraline was slightly more effective but both treatments seemed to work for this population," Mehrotra said in a university news release. "Physicians should select the treatment that is available and acceptable to the patient, recognizing that each comes with its own burdens: Cognitive behavioral therapy needs to be given once a week for 10 sessions, and sertraline is a daily pill that has a higher risk for adverse events such as nausea and dizziness."

The researchers conducted a multicenter, randomized controlled trial involving 184 patients with ESRD who were receiving maintenance hemodialysis at 41 dialysis facilities in three metropolitan areas in the United States. All study participants had been screened for depression and had been identified as having the mood disorder.

ASCEND (A Trial of Sertraline vs Cognitive Behavioral Therapy for End-stage Renal Disease Patients with Depression) had two phases. In the first phase, researchers randomly assigned patients in a 1:1 ratio either to undergo an engagement interview at which their acceptance of treatment for depression was assessed or to have a control visit, stratified by study site.

There was no difference in the primary endpoint for phase 1, which was the proportion of patients who accepted depression treatment within 28 days of the intervention, within or outside of the trial. Specifically, 66% of patients in the engagement group accepted treatment vs 64% in the control group (P = .77).

"I was surprised by how many people accepted treatment," Mehrotra said, noting his earlier research in which only 17% of patients who were receiving dialysis and who had been diagnosed with depression had chosen treatment.

In phase 2 of the trial, patients were randomly assigned in a 1:1 ratio to receive either CBT weekly during dialysis for 10 weeks (n = 60) or sertraline once daily (n = 60), stratified by study site and phase 1 assignment. Sertraline dosage began at 25 mg/day for the first week and was titrated to 200 mg/day if tolerable. During this phase, the researchers compared the efficacy of CBT and sertraline. Twenty study participants who declined treatment within or outside the study enrolled in the observation group, which received no treatment, and 44 patients withdrew from the trial.

During phase 2, the primary outcome was score on the 16-item Quick Inventory of Depressive Symptoms–Clinician-Rated (QIDS-C) at 12 weeks. Scores on the QIDS-C decreased for patients in the CBT group (baseline, 12.2 [standard deviation (SD), 5.1]; 12 weeks, 8.1 [SD, 5.1]) and in the sertraline group (baseline, 10.9 [SD, 4.9]; 12 weeks, 5.9 [SD, 4.5]).

Depression scores at 12 weeks were lower in the group that received sertraline (effect estimate vs CBT, −1.84; 95% confidence interval, −3.54 to −0.13; P = .035).

"Several secondary end points also differed between the groups, but their statistical significance was attenuated in analyses accounting for data missingness," Jennifer E. Flythe, MD, MPH, from the University of North Carolina School of Medicine and the University of North Carolina, Chapel Hill, writes in an accompanying editorial.

"The proportion of patients with a decrease in QIDS-C score of at least 50% or a QIDS-C score less than 5 at 12 weeks was greater in the sertraline group, but the estimates were imprecise and had wide CIs [confidence intervals]," the researchers explain.

There were no changes in QIDS-C scores among those who declined treatment and who agreed to be followed longitudinally (n = 20; QIDS-C score: baseline, 7.8 [SD, 2.8]; 12 weeks, 7.9 [SD, 4.0]).

Depression Undertreated in Patients With Renal Failure on Dialysis

Although depression is thought to affect a significant proportion of patients in this population, Mehrotra said many patients have untreated depression because clinicians may not recognize depression and patients may be reluctant to disclose their symptoms. In addition, quality data showing depression treatments are effective among this patient population have been insufficient.

The Centers for Medicare & Medicaid Services requires Medicare beneficiaries who receive dialysis to be screened each year for depression, but it is not always clear who should be responsible for that assessment, Mehrotra said. "Many dialysis patients have no primary care doctor, and we nephrologists have not been trained in how to treat people for depression and/or make those treatments available. I think we'll have to get out of our comfort zone in that way."

Clinicians Can Feel Comfortable With Both Treatments

"The study by Mehrotra and colleagues has many strengths, namely participant diversity, use of a depression screening tool less likely to be influenced by kidney failure–related somatic symptoms, minimal loss to follow-up, and rigorously collected patient-reported outcomes," Flythe writes.

The study also has limitations, among them the lack of a group that received placebo. Those who received no treatment saw no improvement, "suggesting that some treatment was better than no treatment." In addition, the researchers assessed outcomes at 12 weeks — the end of the acute treatment phase — therefore, the researchers were unable to assess whether symptoms recurred over time, Flythe continues.

More than half of patients with depression will experience a recurrence within 6 months if treatment is stopped, therefore, "[q]uestions regarding the duration and stability of the observed responses are particularly germane considering that the treatment effects of CBT and sertraline were only modest.

"Moreover, achievement of clinical remission did not differ substantially between groups, with rates of 36% and 43% for CBT and sertraline, respectively. Such an incomplete response may partially explain the lack of substantial change in secondary outcomes. Combination therapy (pharmacologic and behavioral) may be needed to yield full remission," Flythe writes.

"Of most importance, the study provides equipoise for clinicians choosing between CBT and sertraline to treat depressive symptoms. The small differential efficacy across treatment groups is of questionable clinical significance, suggesting that clinicians may offer both therapeutic options without concern for compromising outcomes," Flythe concludes.

The study received funding from the Patient-Centered Outcomes Research Institute, the Dialysis Clinic Inc, and the Kidney Research Institute (a collaboration of UW Medicine and Northwest Kidney Centers in Seattle). The original article contains a full listing of the study authors' relevant financial relationships. Flythe have disclosed no such relationships.

Ann Intern Med. Published online February 25, 2019. Abstract, Editorial

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