Nicotine Patch for Depression

Overseen By Warren Taylor, MD,MHSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must be taking: SSRI, SNRI

Must not be taking: Stimulants, Bupropion

Disqualifiers: Psychosis, Neurological disorders, Substance use, 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

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 is an open-label, extension to the blinded Depressed MIND 3 (Depressed Mood Improvement through nicotine dosing) study. It will evaluate longer-term safety and efficacy of Transdermal Nicotine Patches for potential benefit in cognitive and depression outcomes in elderly depressed participants. Subjects complete blinded randomized trial of Depressed MIND-3 will be eligible for continuation in this extension. This extension study will consist of up to 12 weeks of treatment and a 3 -week safety follow-up period.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of an allowed SSRI or SNRI for at least 8 weeks, so you can continue those medications. However, you cannot use other medications for depression or ADHD that you do not want to stop, except for short-acting sedatives.

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 D Taylor

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for people aged 60 or older with major depressive disorder, who have been on a stable dose of certain antidepressants for at least 8 weeks. They must score ≥15 on the MADRS and ≥24 on the MMSE, speak English fluently, and not use tobacco or nicotine in the past year. Exclusions include substance abuse disorders, recent acute grief, other psychiatric disorders except GAD within depression, MRI contraindications, allergy to nicotine patches, and living with smokers.

Inclusion Criteria

Fluent in English

I have been diagnosed with major depression.

Cognition: Mini-Mental State Examination (MMSE) score ≥ 24

Exclusion Criteria

MRI contraindication

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

I have a primary neurological disorder like dementia, stroke, or epilepsy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transdermal nicotine patches with dose titration from 3.5mg to 14mg over 12 weeks

12 weeks

Visits approximately every 3 weeks

Taper

Dose is slowly tapered over 2-3 weeks

2-3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

Treatment Details

Interventions

• Transdermal Nicotine Patch

Trial Overview The study tests if Transdermal Nicotine Patches can improve mood and cognitive performance in elderly individuals with depression by enhancing Cognitive Control Network function. It's an open-label extension of a previous blinded study where participants will receive up to 12 weeks of treatment followed by a safety follow-up.

Participant Groups

Group I: Transdermal Nicotine Patch Experimental Treatment 1 Intervention

Participants will wear nicotine transdermal patches daily for 12-15 weeks. Participants will apply a study patch each morning and remove at bedtime. Active dose will titrate up from 3.5mg to 7mg, and then can optionally be further titrated to a maximum dose of 14mg. After week12, the dose will be slowly 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 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 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 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. England pubmed.ncbi.nlm.nih.gov

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

2. India pubmed.ncbi.nlm.nih.gov

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

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

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

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. Australia pubmed.ncbi.nlm.nih.gov

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

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]