Nicotine Patch for Depression

Overseen By Amy C Janes, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: National Institute on Drug Abuse (NIDA)

Must be taking: Serotonin modulators

Must not be taking: Anticholinergics, Dopamine enhancers, Benzodiazepines

Disqualifiers: Suicidal ideation, Schizophrenia, Bipolar, others

Compensation: Varies

Number of Visits: 2

Duration: 1 year

620 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how nicotine affects symptoms of depression and brain function in individuals with and without major depressive disorder (MDD). Participants will use either a nicotine patch (a form of nicotine replacement therapy) or a placebo to assess the impact on mood and brain activity. The study is open to individuals aged 18 to 60 who do not smoke or use nicotine products. Participants will attend several study visits, undergo MRI scans, and complete computer tasks. As an unphased trial, this study provides a unique opportunity to contribute to understanding nicotine's effects on mood and brain function.

Will I have to stop taking my current medications?

The trial allows participants with depression to continue their current stable serotonin modulating medications (like SSRIs or SNRIs) as long as there have been no changes in the last 2 months. However, you cannot use certain other medications, like those that enhance dopamine, before the scans.

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

Research has shown that nicotine patches are generally safe for use. Studies have found that most people tolerate them well. One study found that using nicotine patches openly improved depression in older adults without major safety issues. Another study showed that nicotine patches helped some people quit smoking without serious side effects. While mild side effects, such as skin irritation at the application site, may occur, serious problems are rare. Participants should monitor how they feel and report any side effects to the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of nicotine patches for depression because they offer a novel approach compared to traditional antidepressants, which typically target neurotransmitters like serotonin or norepinephrine. The nicotine patch, combined with the medication mecamylamine, could potentially act on nicotinic acetylcholine receptors in the brain, providing a new mechanism of action for alleviating depressive symptoms. This method might offer an alternative for individuals who do not respond well to existing treatments or are looking for options with different side effect profiles. Additionally, the use of a patch provides a non-invasive and easy-to-use delivery method, which could improve patient adherence to the treatment.

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

Research has shown that nicotine patches, which participants in this trial may receive, might improve mood and brain function. In one study, about 87% of participants had a strong positive response, and more than half experienced fewer depression symptoms. Another study suggested that nicotine can help the brain manage emotions and thoughts, potentially benefiting people with depression. Additionally, nicotine patches can ease withdrawal symptoms for those quitting smoking, which might also help with depression. These findings suggest that nicotine patches could effectively treat depression symptoms. ^{1 2 3 6 7}

Who Is on the Research Team?

Amy C Janes, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60, with or without Major Depressive Disorder (MDD), who don't smoke or use nicotine products. Participants should be generally healthy and not pregnant. Those with MDD can be on stable SSRI/SNRI medications, while control participants must have no current/lifetime MDD diagnosis.

Inclusion Criteria

I have never been diagnosed with major depressive disorder.

Have a Breath Alcohol Value of 0 on all study visit days involving scanning

Absence of pregnancy and breastfeeding

Exclusion Criteria

I have thoughts of harming myself and need more than outpatient care.

I haven't taken any anticholinergic or dopamine-enhancing drugs in the last week.

Current use of illegal drugs other than marijuana

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI scans with administration of nicotine or placebo to assess neurobiological impact

1 year

2 or 3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mecamylamine
• Nicotine Patch
• Placebo Nicotine Patch

Trial Overview The study tests how nicotine affects depression symptoms and brain function in individuals with MDD compared to healthy controls. It involves MRI scans after taking either a placebo or a real nicotine patch, without knowing which one they've received.

How Is the Trial Designed?

Group I: Arm 2: Nicotine Patch Experimental Treatment 1 Intervention

Nicotine Patch + Placebo Pill

Group II: Arm 1: Placebo Placebo Group 1 Intervention

Placebo patch + Placebo Pill

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a study of 21 patients with major depressive disorder (MDD) who were not responding to selective serotonin reuptake inhibitors (SSRIs), the nicotinic antagonist mecamylamine hydrochloride (MEC) showed a significant reduction in depressive symptoms compared to placebo over an 8-week trial.

While 45.5% of patients taking MEC experienced a 50% or more decrease in symptoms, this was not statistically significant compared to the 10% in the placebo group; however, MEC may still be a promising augmentation strategy for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. George, TP., Sacco, KA., Vessicchio, JC., et al.[2022]

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]

In a study involving 100 smokers, the combination of a nicotine inhaler and fluoxetine did not significantly improve smoking cessation rates compared to a nicotine inhaler and placebo, with sustained abstinence rates being similar across both groups.

Fluoxetine may be beneficial for smokers with higher depression scores, as it appeared to increase abstinence rates in this subgroup, suggesting that antidepressants could help specific populations when quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial. Blondal, T., Gudmundsson, LJ., Tomasson, K., et al.[2019]

In a study of 48 healthy smokers, combining mecamylamine (a nicotine antagonist) with a nicotine skin patch significantly increased continuous smoking abstinence rates at 7 weeks (50% vs. 16.7% for placebo), suggesting enhanced efficacy for smoking cessation.

Mecamylamine not only improved long-term abstinence rates at 6 and 12 months but also reduced cravings and negative feelings associated with withdrawal, indicating its potential to improve the overall smoking cessation experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. Rose, JE., Behm, FM., Westman, EC., et al.[2019]

In a pilot study involving 7 non-medicated nonsmokers with major depressive disorder, both nicotine patch therapy and placebo resulted in a significant reduction in depressive symptoms as measured by the Hamilton Rating Scale for Depression (HRSD) by Day 1.

Despite the small sample size, the results suggest that nicotine patches may have a rapid effect on depressive symptoms, but further research with a larger group is necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study. Cox, LS., Patten, CA., Krahn, LE., et al.[2019]

Nicotine replacement therapies, including a new nicotine vapor inhaler and sublingual nicotine tablets, have shown effectiveness in treating nicotine dependence, with the vapor inhaler delivering nicotine to the oral mucosa and the sublingual tablet demonstrating efficacy in a placebo-controlled trial.

Combining pharmacotherapies, such as nicotine replacement with bupropion or mecamylamine, may enhance treatment outcomes by occupying more nicotine receptors, which could help reduce smoking rewards and support cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New medications for nicotine dependence treatment. Hurt, RD.[2019]

In a study of 289 smokers, the use of a transdermal nicotine patch significantly improved smoking cessation rates compared to a placebo, with 53% abstinent at 6 weeks versus only 17% in the placebo group.

The nicotine patch was found to be safe, with very few participants withdrawing due to side effects, indicating it is an effective option for helping individuals stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A double-blind trial of nicotine patches in smoking cessation]. Tønnesen, P., Nørregaard, J., Simonsen, K., et al.[2015]

Nicotine replacement therapy (NRT) has evolved significantly over the past decade, with new delivery methods like mouth sprays, films, and electronic cigarettes showing promise in aiding smoking cessation and harm reduction.

The article reviews the efficacy and tolerability of these novel NRT products, highlighting their advantages and disadvantages compared to traditional NRT forms, which can help inform users about their options for quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel delivery systems for nicotine replacement therapy as an aid to smoking cessation and for harm reduction: rationale, and evidence for advantages over existing systems. Shahab, L., Brose, LS., West, R.[2022]

In a study of 38 non-medicated individuals with Major Depressive Disorder, those using transdermal nicotine patches had a lower smoking relapse rate (22%) compared to the placebo group (50%) after a target quit date.

While nicotine patches did not significantly improve mood or withdrawal symptoms for those who remained abstinent, they did not lead to increased depression, suggesting a potential safety benefit in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression. Thorsteinsson, HS., Gillin, JC., Patten, CA., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4410859/

Long-term Nicotine Replacement Therapy This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches ...

2. 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 ...

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

Depressed Mood Improvement Through Nicotine Dosing 3 The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S009545430570124X

Tobacco cessation among patients with depression A study of nicotine gum combined with nicotine patch found that this strategy alleviated the discomfort of nicotine withdrawal, including symptoms of dysphoria.

5. acpjournals.org acpjournals.org/doi/10.7326/0003-4819-152-3-201002020-00005

Effectiveness of Extended-Duration Transdermal Nicotine ... The current data are consistent with a meta-analysis indicating that about 50% of relapses could be averted with extended nicotine patch ...

6. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/nicotine-patch

Nicotine Patch - an overview Clinical studies have shown that about 7.2% of patients in double blind studies successfully stop smoking compared to about 5.8% on placebo. Nicotine gum and ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/67/NCT04433767/Prot_SAP_001.pdf

depressed mood improvement through nicotine dosing 2 In our initial pilot trial in LLD (1), we demonstrated that open-label administration of transdermal nicotine patches safely improved depression severity. We ...