Nicotine for Depression

(VATMDDNicotine Trial)

Overseen By Julianna Lizzul

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stony Brook University

Must not be taking: Antidepressants, Cholinergics

Disqualifiers: Nicotine use, Major psychiatric diagnosis, 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

Duration: 8 days

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how nicotine might alleviate depression by examining its effect on specific brain cells that use acetylcholine, a chemical involved in mood and memory. Participants with Major Depressive Disorder will use nicotine patches for 8 days, with brain activity measured before and after treatment. Individuals with depression who aren't using nicotine or certain medications might be suitable for this study. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

If you have Major Depressive Disorder (MDD) and are currently on effective antidepressant medications, you cannot participate in the trial. The trial requires that you are not using medications that target the cholinergic system.

What is the safety track record for nicotine?

Research has shown that using nicotine, especially through skin patches, is generally safe for people with Major Depressive Disorder (MDD). In past studies, these patches did not cause major safety problems. For instance, one study found no serious side effects when people with depression used nicotine patches.

However, individual reactions can vary. Some studies suggest that nicotine might not be more effective than a placebo (a dummy treatment) for easing depression symptoms, but it was usually well-tolerated. Another study found that using nicotine patches over time led to many people with mood disorders feeling better and having their symptoms disappear.

In summary, while nicotine patches seem safe for people with depression, individual experiences can vary. Discussing the possible risks and benefits with a healthcare provider before joining a trial is always advisable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Major Depressive Disorder, which typically involve antidepressant medications like SSRIs or therapy, nicotine is being explored as a potential new option. Researchers are excited about nicotine because it targets the brain's cholinergic system, which might play a role in mood regulation, offering a novel mechanism of action. Additionally, nicotine patches provide a rapid delivery method, potentially offering quicker symptom relief compared to traditional antidepressants that may take weeks to show effects.

What evidence suggests that nicotine might be an effective treatment for depression?

Research has shown that nicotine patches might help treat depression. One study found that people with depression who used nicotine patches felt better, with 86.7% showing significant improvement and 53.3% experiencing a full recovery. Another study found that nicotine patches reduced the severity of depression and related symptoms. In this trial, participants with Major Depressive Disorder will receive interventional treatment with transdermal nicotine patches. Additionally, short-term use of nicotine patches improved mood in non-smoking individuals with depression. These findings suggest that nicotine could be a useful treatment for depression, especially in boosting mood and mental functions. ^{2 3 4 5 6}

Who Is on the Research Team?

Ramin Parsey, MD, PhD

Principal Investigator

Stony Brook University

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder or depression. Participants will use a nicotine patch and undergo PET scans using [18F]VAT to study the effects on brain cells related to mood and wakefulness.

Inclusion Criteria

I am between 18 and 65 years old and not experiencing depression.

For Participants with MDD: Score of at least 29 on the Montgomery-Asberg Depression Rating Scale (MADRS)

I am between 18 and 65 years old with major depressive disorder.

Exclusion Criteria

For Participants with MDD: Significant risk for suicide

For Participants with MDD: Any MRI contraindications, including recent tattoos, metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI

For Participants with MDD: Any PET contraindications, including exceeding research exposure limits, pregnancy, breastfeeding, or planning to conceive during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the MDD arm receive interventional treatment for 8 days with transdermal nicotine patches and two PET scans with [18F]VAT tracer

8 days

Follow-up

Participants are monitored for changes in depression severity using the Hamilton Depression Rating Scale-17

2-4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine

Trial Overview The trial tests if nicotine patches can improve symptoms of depression by affecting certain nerve cells in the brain. It involves before-and-after brain imaging (PET scans) with a tracer called [18F]VAT to observe changes.

How Is the Trial Designed?

Group I: Major Depressive Disorder (MDD) Experimental Treatment 2 Interventions

This arm consists of participants diagnosed with Major Depressive Disorder. Participants in the MDD arm will receive interventional treatment for 8 days with transdermal nicotine patches. Participants in the MDD arm will also receive two PET scans with \[18F\]VAT tracer: one at baseline and one post-treatment.

Group II: Control Experimental Treatment 1 Intervention

This arm consists of non-depressed participants. These participants will receive one PET scan utilizing tracer \[18F\] VAT to measure cholinergic terminal density.

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6129985/

Transdermal Nicotine for the Treatment of Mood and Cognitive ... Open-label administration of transdermal nicotine in LLD resulted in a robust response (86.7%) and remission rates (53.3%), with improvement occurring as early ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165032724010826

Effects of open-label transdermal nicotine antidepressant ... Augmentation with open-label transdermal nicotine patches improved depression severity and secondary affective symptoms.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05746273

Depressed Mood Improvement Through Nicotine Dosing 3 This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported ...

4. nature.com nature.com/articles/1395625

The Effects of Transdermal Nicotine Therapy for Smoking ... (1995) reported that short-term administration (24 hours up to 4 days) of nicotine patches improved mood in non-smoking depressed patients ...

5. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.20230855

Effects of Varenicline, Bupropion, Nicotine Patch, and ... The main and secondary efficacy endpoints were biochemically confirmed continuous abstinence status for the final 4 weeks of treatment (weeks 9– ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39659160/

Effects of Varenicline, Bupropion, Nicotine Patch, and Placebo ... All medications were generally safe in both MDD cohorts. NRT and bupropion were not more effective than placebo for those with current MDD.