CONCORD Trial Results in CKD Depression, With Susan Hedayati, MD, MHSc

Neither behavioral activation therapy (BAT) nor bupropion, started alone and escalated to combination therapy when needed, improved depressive symptoms more than control at 16 weeks in patients with chronic kidney disease (CKD) and major depressive disorder (MDD).¹ The findings from the randomized, double-blind CONCORD trial add to a series of negative depression trials in this population.

Susan Hedayati, MD, MHSc, vice dean for research and professor of medicine in nephrology at Stony Brook University Renaissance School of Medicine, presented the data at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, and discussed the trial in an interview with HCPLive. In her view, the results send investigators back to the drawing board on treating depression in CKD.

Why CONCORD Moved Beyond Sertraline for Depression in CKD

“We saw that not only did sertraline not improve depressive symptoms in that patient population, but it actually led to more GI adverse effects like nausea and vomiting, which is really problematic, especially in our patients as they get closer to stage 5 CKD and develop uremia,” Hedayati said.

That earlier trial, the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), randomized 201 patients with CKD who were not receiving dialysis to sertraline or placebo. It found no significant benefit with sertraline.³ CAST was an exception: depression diagnosed by clinical interview affects about 1 in 5 patients with CKD,² yet these patients have largely been excluded from large antidepressant trials because of safety concerns at low glomerular filtration rate (GFR).

For CONCORD, the investigators turned to bupropion, a non-SSRI antidepressant that Hedayati said has shown efficacy comparable to SSRIs in the general population with fewer adverse effects. They paired it with BAT, a form of cognitive behavioral therapy that requires fewer sessions and places less burden on patients with CKD.

“We noticed that patients with advanced CKD, some of them prefer talk therapy, and some of them prefer, ‘Just give me another medication for my depression,’” Hedayati said. “So we thought if either arm was more efficacious than control, then the patients can choose which one they wanted to try first before having to do the combination therapy.”

Because monotherapy alone often fails to bring depression into remission, patients who had not responded by the midpoint of the trial received both treatments.

CONCORD Trial Design: BAT, Bupropion, and Attention Control

The multicenter, 16 week trial screened 4360 people with CKD stages G3b to G5D using the Quick Inventory of Depressive Symptomatology (QIDS). It randomized 202 patients with MDD to 1 of 3 arms:

• Strategy 1: BAT plus placebo.
• Strategy 2: bupropion XL 150 mg daily plus clinical management.
• Control: placebo plus clinical management.

Clinical management served as an attention control. Patients in either active arm who had not reached remission at 8 weeks went on to receive both bupropion and BAT.

Hedayati said the 150 mg bupropion dose is the one recommended for patients with GFR <45. Clinical management sessions were delivered by video at the same weekly frequency as BAT so that patient contact was matched between arms. The primary outcome was the change in QIDS score from baseline to week 16. Secondary outcomes were the change at week 8 and safety.

The intention-to-treat analysis included 201 patients. Of these, 36% had stage G3b disease, 43% had G4, 11% had G5 not on dialysis, and 10% were receiving dialysis. Mean baseline QIDS scores were similar across arms:

• Strategy 1 (n = 70): 14.3 (SD, 2.6)
• Strategy 2 (n = 68): 14.8 (SD, 3.0)
• Control (n = 63): 15.0 (SD, 3.0)

Mean participation time was 15.2 weeks and did not differ between arms.

BAT Edges Out Control at 8 Weeks but Not at 16 Weeks

At 16 weeks, QIDS scores had fallen by almost the same amount in every arm:

• Strategy 1: 5.9 points (95% CI, −7.0 to −4.7)
• Strategy 2: 5.7 points (95% CI, −6.7 to −4.6)
• Control: 5.9 points (95% CI, −6.9 to −4.9)

The BAT strategy did not differ from control (arm effect, P = .4; arm by week effect, P = .2).

The picture was different at 8 weeks. Scores had changed by −5.4 (95% CI, −6.6 to −4.3) with BAT, −3.8 (95% CI, −4.7 to −3.0) with bupropion, and −4.9 (95% CI, −5.9 to −4.0) with control. BAT produced greater improvement than control (arm effect, P = .003; arm by week effect, P = .01), while bupropion produced less (arm effect, P = .02). Remission at 8 weeks was reached by 26% of patients in the BAT arm vs 6% in the bupropion arm (P = .002).

Hedayati noted that the 8 week BAT difference, although statistically significant, fell short of the 2 point QIDS change the investigators considered clinically meaningful.

Bupropion was also associated with more adverse events than BAT. Insomnia occurred in 13% vs 3% of patients (P = .03), and confusion in 7% vs 0% (P = .03). The investigators concluded that BAT improved MDD symptoms more than control at 8 weeks, but neither strategy was superior to control at 16 weeks.

Editor’s Note: Hedayati reports no relevant disclosures

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