Antidepressants for Depression

(NBOLD Trial)

Overseen By Darlene Winkelman

Age: 65+

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates how stress affects mood and thinking in older adults with depression. Researchers are testing three antidepressants—Bupropion, Desvenlafaxine, and Sertraline—to determine their effectiveness in managing these effects. The goal is to better understand the brain changes involved and develop future prevention strategies. The trial seeks participants who have experienced major depression and can read and write English. Participants should not have a history of alcohol or drug dependence or certain brain conditions like epilepsy or dementia. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiding researchers in understanding how it benefits more patients.

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 is the safety track record for these treatments?

Research has shown that bupropion, desvenlafaxine, and sertraline are FDA-approved antidepressants with some safety information available. Studies indicate that bupropion commonly causes headache, dry mouth, and nausea, with a small risk of suicidal thoughts in some individuals, particularly young adults. Desvenlafaxine is generally safe and well-tolerated, with nausea and trouble sleeping as common side effects. Sertraline also has a good safety record, with nausea, diarrhea, and increased sweating being the most common side effects. Overall, these medications have been widely used and are considered safe for treating depression in adults. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the antidepressants Bupropion, Desvenlafaxine, and Sertraline because they offer varied mechanisms of action compared to traditional treatments for depression. While many antidepressants primarily target serotonin levels, Bupropion also affects norepinephrine and dopamine, potentially offering relief for those who don't respond to typical serotonin-focused medications. Desvenlafaxine, an SNRI, works on both serotonin and norepinephrine, providing a dual approach that may enhance its effectiveness for certain individuals. Sertraline, a well-known SSRI, is distinguished by its favorable side-effect profile and efficacy in treating a broad spectrum of depressive symptoms. These options provide tailored approaches that can be more effective depending on the patient's specific needs.

What is the effectiveness track record for these antidepressants in treating depression?

In this trial, participants will receive FDA-approved antidepressants. Previous studies have shown that bupropion effectively reduces symptoms of depression and works similarly to other antidepressants. Desvenlafaxine significantly improves depression, particularly in younger individuals and those with more severe symptoms. Research also shows that it can enhance overall well-being. Sertraline, another antidepressant, has proven to lower depression scores and help prevent symptoms from returning, especially compared to a placebo. These findings indicate that bupropion, desvenlafaxine, and sertraline are all effective for treating depression. ^{3 6 7 8 9}

Who Is on the Research Team?

David Steffens, M.D.

Principal Investigator

UConn Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4837968/

Bupropion: a systematic review and meta-analysis of ... Bupropion was efficacious in reducing depression scores in 24 of the 27 trials, and, where evaluated, showed comparable levels of efficacy to the other classes ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10317506/

Bupropion Mediated Effects on Depression, Attention Deficit ... Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder.

3. psychiatryadvisor.com psychiatryadvisor.com/features/bupropion-for-treatment-resistant-depression/

Bupropion for Treatment-Resistant Depression There was a significant improvement in depressive symptoms, as shown by a decrease in PHQ-9 scores from a mean (SD) of 15.3 (5.3) prior to the ...

4. en.wikipedia.org en.wikipedia.org/wiki/Bupropion

Bupropion Some peer-reviewed studies suggest the quality of evidence is low. Some meta-analyses report that bupropion has an at-most small effect size for depression.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2009/018644s039s040.pdf

WELLBUTRIN - accessdata.fda.gov The efficacy of WELLBUTRIN has been established in 3 placebo-controlled trials, including 2 of approximately 3 weeks' duration in depressed inpatients and one ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470212/

Bupropion - StatPearls - NCBI Bookshelf - NIH Bupropion is generally avoided due to limited safety data.[25]. Breastfeeding ... Bupropion: efficacy and safety in the treatment of depression. Actas ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/bupropion-oral-route/description/drg-20062478

Bupropion (oral route) - Side effects & dosage Bupropion may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal ...

8. webmd.com webmd.com/drugs/2/drug-13509/wellbutrin-oral/details

Bupropion (Wellbutrin, Zyban, and others) - Uses, Side ... Bupropion may cause suicidal thoughts or actions in a small number of people. Depression or other serious mental health conditions are the ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0149291800883010

Safety profile of sustained-release bupropion in depression Across studies, the most frequently reported adverse events were headache, dry mouth, and nausea. The incidence of adverse events was similar (≤5% difference) ...