Nicotine Patch for Depression

Overseen By NIDA IRP Screening Team

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

420 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Nicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD. Objective: To understand how nicotine affects symptoms of depression and related brain function. Eligibility: People aged 18 to 60 years, at the time of consent, with and without MDD who do not smoke cigarettes or use other nicotine products. Design: Participants will have 2 or 3 study visits over 1 year. Participants will have 2 MRI scans no less than 4 days apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs. Before each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan. For each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours. Participants will answer questions about their thoughts, feelings, and behaviors before and after each scan. They will have a blood test after each scan.

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.

What data supports the effectiveness of the nicotine patch treatment for depression?

Research suggests that nicotine patches may help reduce depressive symptoms in nonsmokers with major depressive disorder, as seen in a small study where participants showed a decrease in depression scores. However, the study was small and needs further replication to confirm these findings. ^{1 2 3 4 5}

Is the nicotine patch safe for humans?

The nicotine patch has been used safely for smoking cessation, with studies showing it is generally well-tolerated. In a study, only a few participants stopped using it due to side effects, indicating it is safe for most people. ^{3 5 6 7 8}

How does the nicotine patch treatment for depression differ from other treatments?

The nicotine patch for depression is unique because it uses nicotine, typically known for smoking cessation, to potentially influence mood by acting on nicotinic acetylcholine receptors, which may have antidepressant effects. This approach is different from standard antidepressants that usually target serotonin or dopamine pathways. ^{1 3 4 5 9}

Research Team

Amy Janes, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression. [2015]

2. England pubmed.ncbi.nlm.nih.gov

The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study. [2019]

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

Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. [2019]

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

New medications for nicotine dependence treatment. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial. [2019]

6. 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]

7. Denmark pubmed.ncbi.nlm.nih.gov

[A double-blind trial of nicotine patches in smoking cessation]. [2015]

8. New Zealand 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. [2022]

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

Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. [2022]