Dr. Madhukar Trivedi and colleagues investigated the effectiveness of sertraline to treat depressive symptoms in patients with Chronic Kidney Disease. The results of the new study, published in JAMA, indicate that sertraline does not significantly reduce depressive symptoms in this population. The authors, therefore, do not recommend sertraline for patients with Chronic Kidney Disease experiencing depression.
“These results provide evidence regarding the lack of efficacy of sertraline among patients with non-dialysis-dependent CKD [Chronic Kidney Disease] that would change clinical practice,” write the researchers.
The senior author of the study, Dr. Madhukar Trivedi, is a professor and Chief of the Division of Mood Disorders in the Department of Psychiatry at the University of Texas Southwestern Medical Center. He is a renowned researcher on the efficacy of depression treatments, especially antidepressant medication, and reports being an “advisor or consultant” to a number of pharmaceutical companies that manufacture antidepressant drugs.
Dr. Trivedi was a co-principal investigator of the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the largest antidepressant efficacy study ever conducted. The researchers of the STAR*D study used their findings to suggest a 67% remission rate for depressed patients who use antidepressants. However, the STAR*D study’s methodology and the conclusions drawn from the results have been heavily criticized, including calls that the findings be retracted. The present study reports very different outcomes, questioning the effectiveness of sertraline for depressed patients with Chronic Kidney Disease.
The authors report that 15% of the US population has Chronic Kidney Disease. A quarter of individuals with kidney disease also experience depression, which is four times the rate of depression in the general population. Individuals with comorbid kidney disease and depression have worsened patient-centered outcomes and higher rates of hospitalization, dialysis, and death.
The researchers note, “Evidence for placebo-controlled efficacy of commonly used antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is limited among patients with CKD [Chronic Kidney Disease], who generally have been excluded from large randomized trials of antidepressant medication treatment due to safety concerns.”
Therefore, the authors designed The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) to evaluate the effectiveness of sertraline, a widely prescribed SSRI, at reducing depressive symptoms in patients with Chronic Kidney Disease.
The study was a double-blind, placebo-controlled, randomized clinical trial. The authors recruited 201 patients who were non-dialysis dependent in stages 3, 4, or 5 of kidney disease (i.e., moderate to end-stage kidney disease). Participants were randomized to either receive sertraline or placebo for 12 weeks. The researchers measured depressive symptoms using the Clinician Rated Quick Inventory of Depression Symptomatology (QIDS). A total of 193 patients were included in the final analyses.
Findings show no significant difference in depression symptom reduction between the sertraline group and placebo group (QIDS score between-group difference was 0.1 points on a 27 point scale). Remission rates were also not significantly different, nor was there significantly different improvement in overall quality of life or health.
The one exception is that participants taking sertraline reported significantly improved sleep compared to the control group. The researchers describe any effect sertraline may have had as “clinically irrelevant” and conclude, “it is unlikely that sertraline is effective for depression treatment in this patient population.”
The researchers find that participants taking sertraline reported higher rates of nausea, vomiting, and diarrhea. They summarize:
“Although sertraline did not result in increased serious adverse events or bleeding, it did increase the rate of adverse gastrointestinal symptoms. These types of adverse events are particularly undesirable among patients with advanced CKD [Chronic Kidney Disease] because they are already prone to uremic symptoms such as nausea and vomiting.”
The authors speculate why sertraline was ineffective in this population. They highlight that 84% of participants were unemployed, and cite findings from the STAR*D study: “socioeconomic factors such as unemployment were shown to be associated with a low likelihood of antidepressant treatment response.” The researchers also question whether depression experienced by chronically ill individuals is “a different clinical entity” than ‘psychiatric’ Major Depressive Disorder. They state:
“These findings are in line with increasing evidence from well-powered trials among patients with other chronic medical conditions, such as asthma, ischemic heart disease, and congestive heart failure, that found SSRIs were no more efficacious than placebo for treating depression.”
In light of the findings, Trivedi and colleagues recommend, “Future studies need to explore whether non-SSRI medications or nonpharmacological therapies can result in improvement in depressive symptoms among patients with non-dialysis-dependent CKD [Chronic Kidney Disease], who are at a disproportionately higher risk for depression and its complications than the general population.” These findings add to a growing body of literature questioning the efficacy of SSRIs to treat depression.
Hedayati, S. S., Gregg, L. P., Carmody, T., Jain, N., Toups, M., Rush, A. J., … Trivedi, M. H. (2017). Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: The CAST randomized clinical trial. The Journal of the American Medical Association. Advance online publication. (Link)