Antidepressants for Depression

(NBOLD Trial)

Overseen By Darlene Winkelman

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: David Steffens

Disqualifiers: Dementia, Epilepsy, Schizophrenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

75 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will focus on examining effects of stress on long-term mood and cognitive outcomes of late-life depression. It will also example the neural underpinnings of these changes using structural and functional brain imaging. Understanding how effects of stress in older depressed adults, as well as factors that might minimize those effects, lead to particular mood and cognitive outcomes will inform future development of novel prevention strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug bupropion for depression?

Research shows that bupropion, when used in its extended-release form, significantly reduces depression symptoms in patients with major depressive disorder. In one study, patients experienced a 55.3% reduction in depression scores after 8 weeks of treatment, indicating its effectiveness. ^{1 2 3 4 5}

Is bupropion generally safe for humans?

Bupropion is generally considered safe, with minimal adverse events reported in clinical trials. However, in cases of overdose, it can cause serious symptoms like fast heartbeat, drowsiness, hallucinations, and seizures, but patients have recovered without long-term effects. ^{6 7 8 9 10}

What makes the drug Bupropion unique for treating depression?

Bupropion is unique because it is the only antidepressant that primarily affects norepinephrine and dopamine, rather than serotonin, which is the focus of most other antidepressants. This makes it a good option for people who may not respond well to traditional serotonin-based treatments. ^{3 10 11 12 13}

Research Team

David Steffens, M.D.

Principal Investigator

UConn Health

Eligibility Criteria

This trial is for older adults who can read and write English, have a score above 25 on the Mini-Mental State Examination, and are experiencing major depression. It's not suitable for those with lifetime alcohol/drug dependence, untreated endocrine disorders (except diabetes), dementia, or significant brain abnormalities.

Inclusion Criteria

Ability to read and write English

Mini-Mental State Examination >25

I have been diagnosed with major depression.

Exclusion Criteria

I have a condition related to brain abnormalities like epilepsy or Parkinson's.

I have an untreated hormone-related condition, but it's not diabetes.

Lifetime alcohol/drug dependence

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline cognitive testing, stress measures, and functional brain MRI scan

1-2 weeks

Longitudinal Follow-up

Annual cognitive testing and stress measures, with a two-year follow-up MRI scan

5 years

Treatment

Subjects receive FDA-approved antidepressants

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• Bupropion
• Desvenlafaxine
• Sertraline

Trial Overview The study examines how stress affects mood and cognitive outcomes in late-life depression using medications like Sertraline, bupropion, desvenlafaxine. It includes brain imaging to understand the neural basis of these changes.

Participant Groups

Group I: Depressed Experimental Treatment 1 Intervention

Subjects receive FDA-approved antidepressants

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

David Steffens

Lead Sponsor

Trials

1

Recruited

80+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

Wellbutrin (bupropion) shows potential genotoxic effects in cultured human peripheral blood lymphocytes, indicating it may cause chromosomal damage in vitro.

Despite these findings, the study suggests that the cytogenetic effects of Wellbutrin are unlikely to occur in actual patients, implying a safety margin when used as an antidepressant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Potential In vitro Genotoxic and Cytotoxic Effects of Bupropion Hydrochloride (Wellbutrin) in Human Peripheral Lymphocytes and Human Cortical Neuron. Bhattacharya, SK., Nathawat, LS., Damani, P., et al.[2021]

Bupropion SR was found to have the most favorable side effect profile among nine antidepressants studied, while fluvoxamine had the least favorable, indicating that side effects play a crucial role in choosing antidepressant medications.

The study highlights the need for more clinical trials directly comparing the side effects of newer antidepressants, as current data from the Physicians' Desk Reference has limitations in accurately reflecting the side effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the tolerability of the newer antidepressants. Dewan, MJ., Anand, VS.[2022]

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 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 study of 274 adults with major depressive disorder, bupropion XL significantly reduced depressive symptoms, particularly in areas of energy, pleasure, and interest, compared to placebo over 8 weeks.

Bupropion XL was well tolerated, with most adverse events being mild or moderate, and showed higher remission and response rates compared to placebo, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study. Jefferson, JW., Rush, AJ., Nelson, JC., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended-release in patients with major depressive disorder with atypical features. [2013]

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

Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. [2015]

3. India pubmed.ncbi.nlm.nih.gov

Assessment of Potential In vitro Genotoxic and Cytotoxic Effects of Bupropion Hydrochloride (Wellbutrin) in Human Peripheral Lymphocytes and Human Cortical Neuron. [2021]

4. England pubmed.ncbi.nlm.nih.gov

After the failure of citalopram for depression, what next? [2019]

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

Citalopram and bupropion-SR: combining versus switching in patients with treatment-resistant depression. [2022]

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

Evaluating the tolerability of the newer antidepressants. [2022]

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

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

8. Ireland pubmed.ncbi.nlm.nih.gov

Bupropion (Zyban) toxicity. [2013]

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

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

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

Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study. [2019]

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

Use of antidepressants: expansion beyond depression and anxiety. [2022]

12. India pubmed.ncbi.nlm.nih.gov

Comparison of the efficacy of venlafaxine and bupropion in the treatment of depressive episode in patients with bipolar II disorder. [2023]

13. Germany pubmed.ncbi.nlm.nih.gov

Other Antidepressants. [2022]