Nicotine Patch for Depression

(DepMIND3 Trial)

Overseen By Carrie Williams

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must be taking: SSRI, SNRI

Must not be taking: Stimulants, Anticholinergics

Disqualifiers: Psychosis, Tobacco use, Alcohol disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Deficits in cognitive control are core features of late-life depression (LLD), contributing both to emotion dysregulation and problems with inhibiting irrelevant information, conflict detection, and working memory. Clinically characterized as executive dysfunction, these deficits are associated with poor response to antidepressants and higher levels of disability. Improvement of cognitive control network (CCN) dysfunction may benefit both mood and cognitive performance, however no current pharmacotherapy improves Cognitive Control Network deficits in LLD. The study examines the hypothesis that nicotine acetylcholine receptor agonists enhance Cognitive Control Network function. This effect may resultantly improve mood and cognitive performance in LLD. Small, open-label studies of transdermal nicotine (TDN) patches have supported potential clinical benefit and provided support that transdermal nicotine administration engages the Cognitive Control Network. This blinded study will expand past open-label trials supporting potential benefit in LLD. It will examine TDN's effect on depression severity and cognitive control functions measured by neuropsychological testing. The study will evaluate 60 eligible and enrolled participants over a 3-year period.

Will I have to stop taking my current medications?

If you are on a stable dose of an allowed SSRI or SNRI for at least 6 weeks, you can continue taking it. However, you cannot use other medications for depression or ADHD that you do not want to stop, and you must not have used drugs with certain properties in the last 4 weeks.

Is the nicotine patch safe for use in humans?

The nicotine patch is generally considered safe for helping people quit smoking, but it can cause skin reactions like irritation or allergies in some users. Physical activity might affect how much nicotine is released, potentially leading to high levels in the blood, which could cause serious side effects. ^{1 2 3 4 5}

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

The nicotine patch is unique for depression treatment because it delivers nicotine through the skin, which may improve mood and increase REM sleep in depressed patients, unlike traditional antidepressants that are usually taken orally and work through different mechanisms. ^{6 7 8 9 10}

Research Team

Warren Taylor

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for people over 60 with mild depression who've been on a stable dose of certain antidepressants for at least 6 weeks. They must have decent memory function, speak English, and not use tobacco or nicotine products in the past year. Those with serious medical conditions, recent psychotherapy they don't want to pause, exposure to secondhand smoke, or substance abuse issues can't join.

Inclusion Criteria

I have been on a steady dose of certain depression meds for 6 weeks.

Fluent in English

Cognition: MMSE ≥ 24

Exclusion Criteria

I have a brain disorder like dementia, stroke, or epilepsy.

I haven't used certain drugs affecting the brain or liver enzymes in the last month.

Current or past psychosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants apply transdermal nicotine or placebo patches daily, with dose titration over 12 weeks

12 weeks

Regular visits for monitoring and assessments

Tapering

Patch dose is tapered over 2-3 weeks following the treatment phase

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Transdermal Nicotine Patch
• Transdermal Placebo Patch

Trial Overview The study tests if nicotine patches can improve mood and cognitive functions in older adults with depression by activating the Cognitive Control Network. It compares the effects of real nicotine patches against placebo (fake) patches in participants over three years through neuropsychological testing.

Participant Groups

Group I: Transdermal Nicotine Patch Experimental Treatment 1 Intervention

Participants will be randomized to apply nicotine transdermal patches during waking hours. Active dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.

Group II: Transdermal Placebo Patch Placebo Group 1 Intervention

Participants will be randomized to apply placebo transdermal patches during waking hours. Placebo patch titration will mirror the active arm, increasing the dose will titrate up from 3.5mg to 7mg in the first 3 weeks. Doses can be optionally titrated to a maximum of 14mg over 12 weeks, based on tolerability and perceived benefit. After 12 weeks, the patch dose will be tapered over 2-3 weeks.

Transdermal Nicotine Patch is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nicotine Patch for:

• Smoking cessation

Approved in European Union as Nicotine Patch for:

• Smoking cessation

Approved in Canada as Nicotine Patch for:

• Smoking cessation

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study of 201 daily smokers, only 35.3% adhered to the nicotine patch therapy for the first 28 days, highlighting a significant issue with adherence despite the patch's proven safety and effectiveness for smoking cessation.

Common reasons for non-adherence included forgetting to use the patch (30%), disliking side effects (15%), resuming smoking (10%), and financial constraints (7%), suggesting that targeted support and advice from healthcare providers could improve adherence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reasons for non-adherence to nicotine patch therapy during the first month of a quit attempt. Yingst, JM., Veldheer, S., Hrabovsky, S., et al.[2022]

In a study of 186 participants, only 1.6% showed delayed contact sensitization to the nicotine transdermal system, indicating a low risk of allergic reactions.

The transdermal nicotine system was well tolerated, with less than 3% of applications causing nonallergic skin irritation, and all reactions resolved without complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm) Jordan, WP.[2015]

Transdermal nicotine release from two different nicotine patch formulations increases during physical activity, but this increase does not significantly affect overall plasma nicotine levels, indicating a consistent pharmacokinetic profile during rest and exercise.

In a study involving 10 healthy smokers, no adverse events were reported, suggesting that using transdermal nicotine patches during physical activity is safe and does not lead to toxic plasma concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on transdermal nicotine release in healthy habitual smokers. Bur, A., Joukhadar, C., Klein, N., et al.[2019]

Transdermal nicotine therapy significantly increases the chances of quitting smoking, more than doubling success rates in motivated smokers who smoke at least 10-15 cigarettes per day, with an odds ratio of 2.3 after 12 months.

While effective, transdermal nicotine can cause side effects like skin reactions and sleep disturbances, and it is recommended primarily for smokers who struggle to quit through other methods due to its cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pros and cons of transdermal nicotine therapy. Gourlay, S.[2015]

In a study of 14 volunteers with previous skin reactions to nicotine transdermal therapeutic systems (TTS), 5 individuals showed contact sensitization to nicotine, indicating a potential allergic reaction to the treatment.

The study found that irritant reactions due to the occlusive nature of the TTS occurred in 9 subjects, highlighting the need for caution when using nicotine patches, especially in individuals with a history of skin sensitivities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse skin reactions to nicotine in a transdermal therapeutic system. Bircher, AJ., Howald, H., Rufli, T.[2019]

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 study involving eight depressed patients and eight normal volunteers, nicotine patches increased REM sleep in depressed patients without affecting other sleep variables, suggesting a potential benefit for sleep in this population.

Normal volunteers experienced sleep fragmentation and reduced REM sleep time with nicotine patches, indicating that the effects of nicotine on sleep can vary significantly between depressed and non-depressed individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. Salín-Pascual, RJ., de la Fuente, JR., Galicia-Polo, L., et al.[2019]

In a study of 3,281 smokers attempting to quit, nearly 11% used a nicotine patch, with users more likely to be female, white or Asian, and heavier smokers.

The nicotine patch significantly improved smoking cessation rates when used alongside other aids, resulting in an 18.8% abstinence rate compared to 10.9% for those using other aids without the patch.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine patch use in the general population: results from the 1993 California Tobacco Survey. Pierce, JP., Gilpin, E., Farkas, AJ.[2019]

In a study of 158 smokers, transdermal nicotine patches significantly improved smoking cessation rates, with 39% of participants using 24-hour patches and 35% using patches during wakeful hours achieving abstinence, compared to only 13.5% in the placebo group.

The nicotine patches also effectively reduced tobacco withdrawal symptoms during the initial weeks of quitting, demonstrating their safety and efficacy as an adjunct to low-intervention therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of transdermal nicotine as an adjunct in smoking cessation therapy. A double-blind randomized study controlled with placebo]. Daughton, DM., Heatley, SA., Prendergast, JJ., et al.[2015]

Transdermal nicotine delivery systems can significantly aid smoking cessation, achieving abstinence rates of 30 to 41% in the first 6 weeks, compared to only 4 to 21% with placebo, especially when combined with behavioral therapy that can boost initial rates up to 86%.

These systems are generally well tolerated, with local irritation being the most common side effect, and they offer a convenient and unobtrusive method for nicotine replacement therapy, although maintaining long-term abstinence remains a challenge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Palmer, KJ., Buckley, MM., Faulds, D.[2018]

References

1. India pubmed.ncbi.nlm.nih.gov

Reasons for non-adherence to nicotine patch therapy during the first month of a quit attempt. [2022]

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

Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm) [2015]

3. Germany pubmed.ncbi.nlm.nih.gov

Effect of exercise on transdermal nicotine release in healthy habitual smokers. [2019]

4. Australia pubmed.ncbi.nlm.nih.gov

The pros and cons of transdermal nicotine therapy. [2015]

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

Adverse skin reactions to nicotine in a transdermal therapeutic system. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

Effects of transderman nicotine on mood and sleep in nonsmoking major depressed patients. [2019]

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

Nicotine patch use in the general population: results from the 1993 California Tobacco Survey. [2019]

9. Italy pubmed.ncbi.nlm.nih.gov

[Effects of transdermal nicotine as an adjunct in smoking cessation therapy. A double-blind randomized study controlled with placebo]. [2015]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. [2018]