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

Trial Summary

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.

What data supports the effectiveness of the treatment Behavioral Activation Therapy for depression in patients 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 or with antidepressant medication. It has been proven to improve symptoms of depression and quality of life in various settings. ^{1 2 3 4 5}

Is bupropion generally safe for humans?

Bupropion is generally considered safe for humans, with minimal adverse events reported in clinical trials. However, seizures are a known side effect, especially in cases of overdose. ^{6 7 8 9 10}

How is the treatment Behavioral Activation Therapy with Bupropion unique for depression in kidney disease patients?

This treatment combines Behavioral Activation Therapy, which is a simple and cost-effective approach to help people engage in activities that improve mood, with Bupropion, a medication that can boost mood and energy. This combination may offer a novel approach for treating depression in patients with kidney disease, where standard treatments might be limited. ^{11 12 13 14 15}

What is the purpose of this trial?

This trial is testing two new ways to treat depression in people with chronic kidney disease. One method uses therapy sessions over the phone or internet, and the other uses a medication called bupropion. If one method doesn't work after a certain period, the other is added. The goal is to see if these treatments can improve depression and overall health in these patients. Bupropion is a second-generation antidepressant commonly used to treat depression, including in patients with chronic kidney disease.

Research Team

Susan Hedayati, MD

Principal Investigator

Stony Brook University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Internet-Based Behavioral Activation for Depression: Systematic Review and Meta-Analysis. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

A Narrative Review of Empirical Literature of Behavioral Activation Treatment for Depression. [2022]

3. Germany 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Behavioral activation: a strategy to enhance treatment response. [2014]

5. England 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. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Methodologic approach to adverse events applied to bupropion clinical trials. [2013]

7. United States 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. [2020]

8. Singapore pubmed.ncbi.nlm.nih.gov

Charcoal hemoperfusion in bupropion overdose. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Bupropion hydrochloride. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Bupropion exposures: clinical manifestations and medical outcome. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Behavioral activation: Is it the expectation or achievement, of mastery or pleasure that contributes to improvement in depression? [2019]

12. France pubmed.ncbi.nlm.nih.gov

[Behavioral activation programs: A tool for treating depression efficiently]. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Innovations in Practice: A randomised controlled feasibility trial of Behavioural Activation as a treatment for young people with depression. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Feasibility study of a new behavioural activation programme for young people with depressed mood. [2022]

15. Netherlands pubmed.ncbi.nlm.nih.gov

Treating depressive symptoms among veterans in primary care: A multi-site RCT of brief behavioral activation. [2021]