Combination Therapies for Depression with Kidney Disease

(CONCORD Trial)

Recruiting at 3 trial locations

Overseen By Ana Arroyo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stony Brook University

Must not be taking: Anti-arrhythmics, MAO inhibitors, Serotonergics, others

Disqualifiers: Dialysis, Hepatic dysfunction, Seizure disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

201 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks effective treatments for depression in individuals with chronic kidney disease (CKD). Researchers are testing two strategies: one combines Behavioral Activation Teletherapy (a type of talk therapy that encourages positive activities) with the antidepressant bupropion, while the other begins with bupropion and adds the therapy later. The goal is to determine which approach more effectively reduces depression symptoms and improves overall health outcomes in CKD patients. Individuals with CKD who have not undergone dialysis and are currently experiencing depression may qualify to join. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to developing effective depression treatments for CKD.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, including any ongoing antidepressant medications, serotonergic drugs, and some other specific medications listed in the exclusion criteria.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that Behavioral Activation Therapy (BAT) produces positive results for treating depression. This method improves mood by encouraging enjoyable activities and is generally well-tolerated, with few reports of serious side effects.

Research has shown that bupropion, a non-SSRI antidepressant, effectively treats depression. The FDA has approved it for major depressive disorder, indicating its safety for most people. However, some users have reported agitation or irritability, and rare cases of suicidal thoughts have occurred.

Since this trial is in Phase 2, earlier studies have already tested the treatments for safety. This suggests they are likely safe, but more data from this trial will help confirm how well people with kidney disease tolerate these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Behavioral Activation Therapy (BAT) and bupropion in unique ways to tackle depression in patients with kidney disease. Unlike typical antidepressant treatments, which often rely solely on medication, Strategy 1 starts with BAT to engage patients in positive activities, adding bupropion only if needed. Strategy 2 flips this approach, starting with bupropion and integrating BAT later. This trial is particularly promising as it explores whether a blended approach can be more effective for this specific group, potentially leading to faster and more comprehensive relief from depression symptoms.

What evidence suggests that this trial's treatments could be effective for depression in patients with kidney disease?

Research shows that Behavioral Activation Therapy (BAT), one of the treatments in this trial, reduces symptoms of depression. Studies have found that BAT delivered through teletherapy (online sessions) can be as effective as face-to-face therapy. This method has proven successful in various situations, including with older adults and in digital formats.

Bupropion, another treatment option in this trial, is an antidepressant that is not an SSRI (a common type of antidepressant). It has shown positive results in treating depression in people with chronic kidney disease (CKD). Research suggests it can improve mood, enhance thinking skills, and reduce tiredness in CKD patients. Both BAT and bupropion offer new ways to treat depression, especially when standard treatments like SSRIs are ineffective. ^{1 2 5 6 7}

Who Is on the Research Team?

Susan Hedayati, MD

Principal Investigator

Stony Brook University

Are You a Good Fit for This Trial?

Adults aged 18+ with chronic kidney disease stages 3b-5 and a confirmed diagnosis of Major Depressive Disorder. Participants must have a specific level of depressive symptoms, be able to consent, and not be on dialysis. Exclusions include significant liver issues, certain severe diseases, seizure disorders, use of conflicting medications or supplements, substance abuse needing detoxification, psychosis or bipolar disorder history.

Inclusion Criteria

Able to understand and sign informed consent after the nature of the study has been fully explained

I am an adult with chronic kidney disease in stages 3b, 4, or 5 and my kidney function is below normal.

I had a kidney transplant at least 6 months ago, or 3 months ago with a low kidney function confirmed.

Exclusion Criteria

I am taking medication that can affect my heart's rhythm.

I am on long-term dialysis.

I am currently taking medication or supplements that affect serotonin levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive either Behavioral Activation Teletherapy (BAT) plus placebo or bupropion plus Clinical Management for 8 weeks

8 weeks

Visits at weeks 4, 6, and 8

Treatment Phase 2

Non-remitters receive combination therapy with BAT and bupropion for an additional 8 weeks

8 weeks

Visits at weeks 8, 12, and 16

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Behavioral Activation Therapy
• Bupropion
• Clinical Management
• Placebo

Trial Overview The trial is testing the effectiveness of Behavioral Activation Teletherapy (BAT) and bupropion (a non-SSRI antidepressant) against placebo in improving depression in CKD patients. It's structured so that if there's no improvement after 8 weeks for some patients, they'll receive an additional treatment. The study aims to see if these treatments can also improve medication adherence and overall quality of life.

How Is the Trial Designed?

Group I: Strategy 1 Active Control 2 Interventions

Strategy 1: Single-blind Behavioral Activation Therapy plus placebo for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind bupropion (Phase 2) for another 8 weeks.

Group II: Strategy 2 Active Control 2 Interventions

Strategy 2: Double-blind bupropion plus single-blind Clinical Management (CM) attention control for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind BAT (Phase 2) for another 8 weeks.

Group III: Control Placebo Group 2 Interventions

Control: Clinical management attention control plus placebo for 16 weeks

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

A brief version of Behavioral Activation for primary care (BA-PC) was found to significantly improve quality of life and mental health functioning in veterans compared to standard treatment-as-usual (TAU) after 12 weeks, despite both groups showing reductions in depressive symptoms.

The study involved 140 veterans and demonstrated that BA-PC not only maintained reductions in depressive symptoms but also had better treatment retention and feasibility, suggesting it could be a valuable approach for managing depression in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating depressive symptoms among veterans in primary care: A multi-site RCT of brief behavioral activation. Funderburk, JS., Pigeon, WR., Shepardson, RL., et al.[2021]

Behavioral activation (BA) is an effective and affordable psychotherapy for major depressive disorder (MDD), focusing on increasing engagement in rewarding activities and reducing avoidant behaviors.

Randomized controlled trials indicate that BA has a strong therapeutic effect on MDD, making it a viable treatment option, although more research is needed to explore its application in other psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Behavioral activation programs: A tool for treating depression efficiently]. Dondé, C., Moirand, R., Carre, A.[2018]

In a study of 313 patients with major depressive disorder, internet-based behavioral activation significantly reduced depressive symptoms by increasing engagement in enjoyable activities, with a measurable effect observed after 4 weeks.

The findings suggest that clinicians and patients should expect a 4-week period for activation levels to improve before seeing a notable reduction in depression symptoms, which typically occurs around 6 weeks into the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Explaining the Efficacy of an Internet-Based Behavioral Activation Intervention for Major Depression: A Mechanistic Study of a Randomized-Controlled Trial. Fu, Z., Burger, H., Arjadi, R., et al.[2022]

Behavioral activation is an effective treatment for depression that focuses on increasing engagement in pleasurable and meaningful activities, and it can be used alone or alongside antidepressant medications.

The method involves activity monitoring to help patients track their behaviors and moods, which aids in identifying patterns that contribute to their depression, making it a versatile approach even for those with other mental health issues like psychosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral activation: a strategy to enhance treatment response. Sudak, DM., Majeed, MH., Youngman, B.[2014]

This pilot study aims to assess the feasibility of implementing behavioral activation (BA) in a group format for patients with moderate to severe depression, focusing on recruitment, retention, and participant feedback, which is crucial for planning a larger trial.

The study will evaluate changes in mood and quality of life in participants receiving BA alongside usual care, potentially demonstrating BA's effectiveness in improving depression symptoms in a resource-limited setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pragmatic pilot randomized trial to investigate the effectiveness of behavioural activation group therapy in reducing depressive symptoms and improving quality of life in patients with depression: the BRAVE pilot trial protocol. Samaan, Z., Litke, K., McCabe, K., et al.[2020]

In a 9-week randomized controlled trial involving 78 patients with major depression, the study found that both expected mastery and pleasure from behavioral activation tasks were strongly correlated with improvements in depression severity.

The results suggest that the anticipation of pleasure from planned activities may be more important for the effectiveness of behavioral activation than the actual pleasure experienced, highlighting the role of meaningful engagement in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral activation: Is it the expectation or achievement, of mastery or pleasure that contributes to improvement in depression? Furukawa, TA., Imai, H., Horikoshi, M., et al.[2019]

Bupropion is an effective antidepressant that is well-tolerated, showing superior efficacy compared to placebo in clinical trials involving doses of 300-750 mg/d.

It has a safety profile that is favorable compared to traditional antidepressants like amitriptyline and imipramine, with the main risk being seizure induction, which occurs at a frequency similar to imipramine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion hydrochloride. Dufresne, RL., Weber, SS., Becker, RE.[2019]

Internet-based behavioral activation (iBA) significantly reduces depressive symptoms compared to inactive control groups, with a moderate effect size based on a systematic review of 12 randomized controlled trials involving 3274 participants.

iBA also leads to reductions in anxiety and improvements in quality of life and activation, although no significant effects on depressive symptoms were observed at the 6-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Internet-Based Behavioral Activation for Depression: Systematic Review and Meta-Analysis. Alber, CS., Krämer, LV., Rosar, SM., et al.[2023]

Behavioral activation (BA) is an effective standalone psychotherapy for depression, showing comparable efficacy to traditional cognitive-behavioral therapy (CBT) and is recognized as an evidence-based guided self-help intervention.

Further research is needed to understand the neurobiological mechanisms behind BA and to assess the potential for integrating e-mental health applications of BA into China's public healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Narrative Review of Empirical Literature of Behavioral Activation Treatment for Depression. Wang, X., Feng, Z.[2022]

A new behavioral activation (BA) program developed for young people with depression showed promising results, with 36% of participants recovering and being discharged after treatment.

In a feasibility study involving 33 young people, significant improvements were observed in mood and clinician assessments, indicating that less specialized staff can effectively deliver BA, potentially reducing wait times for specialized therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility study of a new behavioural activation programme for young people with depressed mood. Dubicka, B., Marwedel, S., Banares, S., et al.[2022]

A review of 7,348 bupropion-only exposures revealed that while most unintentional exposures resulted in minimal toxicity, 15% of intentional overdoses led to seizures, highlighting the risks associated with misuse.

The data indicated that Wellbutrin SR was the most commonly involved product, and serious clinical effects were more prevalent in intentional overdoses, particularly among teenagers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion exposures: clinical manifestations and medical outcome. Belson, MG., Kelley, TR.[2019]

Behavioural Activation (BA) treatment was found to be acceptable for adolescents with depression, with high adherence rates (median of 7 out of 8 sessions completed) among the 22 participants in the study.

Preliminary results indicated positive changes in depression, self-esteem, and functioning for the BA group compared to usual care, with no reported adverse events, suggesting that BA is a safe and promising intervention for further evaluation in a larger trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovations in Practice: A randomised controlled feasibility trial of Behavioural Activation as a treatment for young people with depression. Kitchen, CEW., Tiffin, PA., Lewis, S., et al.[2021]

Bupropion (Wellbutrin) was evaluated in four double-blind, placebo-controlled trials involving 360 participants, demonstrating minimal adverse events associated with its use.

The adverse events correlated well with the known pharmacological properties of bupropion, indicating a favorable safety profile for this novel antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodologic approach to adverse events applied to bupropion clinical trials. Cato, AE., Cook, L., Starbuck, R., et al.[2013]

A 23-year-old woman experienced severe symptoms, including seizures and altered mental status, after overdosing on bupropion, highlighting the medication's potential for serious side effects.

The patient fully recovered after undergoing hemodialysis 4 hours post-overdose, suggesting that this treatment may be effective in managing bupropion toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Charcoal hemoperfusion in bupropion overdose. Akdemir, HU., Calışkan, F., Duran, L., et al.[2016]

In a study involving 4092 participants with psychiatric disorders, varenicline, bupropion, and nicotine patches were found to be well tolerated and effective for smoking cessation, with no significant increase in neuropsychiatric adverse events compared to placebo.

Varenicline demonstrated superior continuous abstinence rates compared to bupropion, nicotine patches, and placebo, indicating its effectiveness across various psychiatric diagnoses without varying efficacy based on the type of disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric Safety and Efficacy of Varenicline, Bupropion, and Nicotine Patch in Smokers With Psychotic, Anxiety, and Mood Disorders in the EAGLES Trial. Evins, AE., Benowitz, NL., West, R., et al.[2020]

Citations

1. thejcn.com thejcn.com/DOIx.php?id=10.3988/jcn.2024.0148

Behavioral Activation and Brain Network Changes in ... The results showed that the efficacy of BA was comparable to that in pharmacotherapy in the acute treatment of MDD, and better than CT in ...

2. psychiatrist.com psychiatrist.com/pcc/behavioral-activation-teletherapy-for-depression-and-anxiety/

Efficacy of a Behavioral Activation Teletherapy Intervention ... Conclusions: Primary care patients demonstrated improvements in depressive and anxious symptoms throughout BA-based teletherapy. BA teletherapy ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11943665/

Next-Generation Cognitive-Behavioral Therapy for Depression Teletherapy-based CBT is hypothesized to demonstrate similar, if not superior, efficacy outcomes to in-person therapy. Teletherapy provides flexibility, reduces ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11552036/

Behavioral Activation Therapy for Depression Led by Health ... Overall, these findings support the effectiveness and applicability of behavioral activation therapy in treating depression in older adults.

5. jmir.org jmir.org/2025/1/e68054

Effectiveness of Digital Behavioral Activation Interventions ... Conclusions: Digital BA interventions are effective in reducing depressive symptoms and improving QoL in the short- to midterm. However, these ...

6. withpower.com withpower.com/trial/phase-3-renal-insufficiency-chronic-8-2020-fe768

Combination Therapies for Depression with Kidney Disease Behavioral Activation Therapy is shown to be effective in reducing depression by encouraging enjoyable activities that boost mood, and it can be used alone ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06273995

NCT06273995 | Telehealth Behavioral Activation for Teens Behavioral activation is one such empirically supported intervention. Derived from cognitive-behavioral therapy, a well-established treatment for depression ...