Sertraline does not temper depression in patients with chronic kidney disease

Last Updated: 2017-11-07

By Will Boggs MD

NEW YORK (Reuters Health) - Sertraline treatment does not relieve depressive symptoms in patients with chronic kidney disease (CKD) who are not on dialysis, according to results from the CAST randomized trial.

"Our study does not support the use of SSRIs (selective serotonin reuptake inhibitors) such as sertraline for treatment of depression in patients with stages 3B, 4, and 5 non-dialysis CKD, and perhaps these medications should not be added to the long list of other medications that we prescribe to CKD patients because of the risk of increased gastrointestinal side effects," Dr. S. Susan Hedayati from University of Texas Southwestern Medical Center, Dallas, told Reuters Health by email. "These side effects, such as nausea and vomiting, are particularly problematic in patients with advanced stage CKD that are already prone to the development of uremic symptoms."

Up to 25% of patients with CKD have depression, a rate four times higher than that in the general population, yet these patients have generally been excluded from large trials of antidepressant medication because of safety concerns.

Dr. Hedayati and colleagues from three U.S. medical centers conducted a study of 201 patients with non-dialysis-dependent stage 3 (11% stage 3A, 36% stage 3B), stage 4 (36%), or stage 5 (17%) CKD and major depressive disorder (MDD). Participants were randomized to receive sertraline (initially, 50 mg/day, escalated as needed up to 200 mg/day) or matching placebo for 12 weeks.

Of 193 patients in the modified intention-to-treat sample, 92% completed at least 6 weeks and 84% completed all 12 weeks of the study, with a median treatment duration of 84 days. The findings were published online November 3 in JAMA.

Quick Inventory of Depressive Symptomatology-Self-Reported scores at 12 weeks, the primary endpoint, did not differ significantly between the sertraline and placebo groups.

Remission rates for depression were low and statistically similar with sertraline (15.5%) versus placebo (14.6%). The two groups also did not differ in measures of overall functioning, health, and quality of life.

Adverse events were significantly more common with sertraline than placebo (76.1% vs. 60.0%), notably nausea or vomiting (22.7% vs. 10.4%) and diarrhea (13.4% vs. 3.1%).

"These data support previous trials of depression treatment in patients with other chronic medical conditions, such as congestive heart failure and chronic asthma, which also did not show a benefit for treatment of depression with SSRIs over placebo," Dr. Hedayati said. "Perhaps the depression of chronic disease is a different clinical entity than the typical psychiatric depressive disorder and is not amenable to treatment with SSRI medications."

"Until more evidence regarding efficacious treatments becomes available, such therapies as cognitive behavioral therapy (CBT) may be considered," she said. "At least two studies have shown promise for the efficacy of CBT in the treatment of depression in CKD patients on chronic hemodialysis."

Dr. Hedayati advised caution in extrapolating the findings to "patients with earlier stages of CKD with estimated glomerular filtration rate greater than 60, or those who are on maintenance dialysis, given that this trial was conducted in patients with stages 3-5 non-dialysis CKD."

Dr. Carl Peter Walther from Baylor College of Medicine, Houston, Texas, who coauthored a related editorial, told Reuters Health by email, "Patients with moderate depression and non-dialysis CKD should probably not be prescribed sertraline alone as a treatment for depression. It would be reasonable to try under the direction of a psychiatrist other treatments such as psychotherapy." He added that sertraline or other antidepressants could be tried in individual patients, but with especially close monitoring of depressive symptoms and side effects.

"Physicians and patients must demand from pharmaceutical companies and regulatory/governmental bodies that medications (and other treatments) be adequately studied in the populations that will ultimately take them (namely, the high proportion of Americans with CKD and other chronic illnesses)," he said. "Currently, drug trials often exclude these patients, purportedly for safety concerns, but the current system means they are being used in general practice in uncontrolled, often suboptimally monitored 'real-world' situations where they have never been studied for safety or efficacy."

"We must adequately study (randomized controlled trials) therapies in CKD populations, which will require government-sponsored studies for generic therapies (such as sertraline, for which no drug company will pay for any studies) and perhaps regulatory changes to encourage companies to adequately study their treatments in CKD prior to taking to market (or early after approval)," Dr. Walther said. "The current system, with enormous amounts spent on care of CKD patients, but relatively little spent on research, leads to expensive, ineffective care."

Dr. Masao Iwagami from London School of Hygiene and Tropical Medicine, London, UK, who recently reviewed the use of antidepressants in patients with or without CKD, told Reuters Health by email, "In a sense, this result is in line with my clinical impression: bad depression scores among patients with advanced CKD are seemingly due to their physical conditions (i.e., they are simply unwell and answer to any questionnaire negatively) rather than genuine mental-health problems, and therefore cannot be improved by antidepressants."

He suggests trying "non-pharmacological interventions, such as talking therapy and exercise (e.g., yoga). Even if they were not effective (for the same reason as above), at least they would not do harm."

SOURCES: http://bit.ly/2iZ8ACv and http://bit.ly/2AnE0qn

JAMA 2017.