Treating Depression in CKD After CONCORD, With Susan Hedayati, MD, MHSc

With no antidepressant or talk therapy yet shown to outperform control in chronic kidney disease (CKD), clinicians are left weighing whether and how to treat major depressive disorder (MDD), which affects about 1 in 5 of these patients.² The latest negative trial, CONCORD, tested bupropion and behavioral activation therapy (BAT) and found neither superior to control at 16 weeks.¹

Susan Hedayati, MD, MHSc, vice dean for research and professor of medicine in nephrology at Stony Brook University Renaissance School of Medicine, led CONCORD and presented it at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado. In an interview with HCPLive, she outlined how clinicians can approach treatment until better evidence arrives.

Why Depression Treatments May Work Differently in CKD

“So that tells me that maybe the pathophysiological factors that lead to these symptoms in the general population may not be the same as they are in people with CKD or with other chronic diseases,” Hedayati said.

Her group’s earlier Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) found sertraline no better than placebo in 201 patients with CKD who were not receiving dialysis. It also found that sertraline caused more gastrointestinal adverse effects.³ In CONCORD, an early advantage for BAT at 8 weeks did not persist, and bupropion was associated with more insomnia and confusion than BAT.¹

Hedayati said the pattern extends beyond depression. Trials of interventions for other CKD symptoms, including sleep problems and fatigue, have generally been negative or lacked a control arm or a clinically meaningful difference. Depression trials in heart failure, asthma, and coronary artery disease have also come up negative.

Shared Decision Making and a 4 to 6 Week Treatment Trial

“I think we should use a shared decision making approach with the patient, and if they do want to try treatment, offer them one of these medications that we tried before, like sertraline or bupropion, or talk therapy,” Hedayati said. “But the thing to keep in mind is try it for a short duration period, like 4 to 6 weeks, and if the patient doesn’t respond, don’t continue it, because it’s just a treatment burden.”

Talk therapy options include cognitive behavioral therapy or BAT, a shorter form that requires fewer sessions. Hedayati emphasized that the goal of a defined trial period is to avoid keeping patients on a therapy that isn’t helping them.

Starting Sertraline at a Low Dose in Patients With CKD

“Reassess the patient for tolerability and safety,” Hedayati said. “And again, if it’s not working, stop the intervention.”

For SSRIs, she advised starting sertraline at 50 mg daily and increasing gradually, which she described as doubling the dose every 2 weeks, up to a maximum of 200 mg daily. That range mirrors the flexible dosing used in CAST, which started at 50 mg daily and escalated to a maximum of 200 mg daily based on tolerability and response.³

Biomarkers May Identify Who Responds to Depression Treatment in CKD

Hedayati believes the next step is understanding what drives depressive symptoms in CKD, and whether a prediction model can identify subgroups of patients likely to respond to existing treatments. With an NIH R01 supplement to CONCORD, her team is studying circulating serum and inflammatory biomarkers using whole genome profiling, RNA sequencing, and proteomics. The goal is to determine which patients will and will not respond to treatment.

Editors’ Note: Hedayati reports no relevant disclosures with industry.

References

1. Hedayati S, Zhang X, Tuttle KR, et al. CONCORD: a randomized controlled trial of novel therapies for depression in patients with CKD. Abstract FR-OR110. Presented at: American Society of Nephrology Kidney Week 2026; October 21-25, 2026; Denver, CO.

2. Palmer S, Vecchio M, Craig JC, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int. 2013;84(1):179-191.

3. Hedayati SS, Gregg LP, Carmody T, et al. Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: the CAST randomized clinical trial. JAMA. 2017;318(19):1876-1890. doi:10.1001/jama.2017.17131