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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether nicotine patches can improve mood and mental function in older adults with depression. Researchers believe nicotine might enhance the brain's ability to manage emotions and focus, which are often challenging for those with late-life depression. Participants will use either a nicotine patch (transdermal nicotine patch) or a placebo patch to determine any differences in depression symptoms and cognitive performance. The trial seeks individuals aged 60 and over who have mild depression, are on a stable dose of antidepressants, and have not used nicotine in the past year. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings in depression treatment.

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

Research has shown that a nicotine skin patch might help with depression and thinking problems in older adults. Previous studies found that many people responded well to this treatment. In one study, 86.7% of participants felt better, and 53.3% even saw their symptoms disappear.

However, it's important to know that nicotine patches, like other nicotine replacement therapies, can have some side effects. Reports have mentioned a higher chance of fast or irregular heartbeats and chest pain. A review of 12 studies observed these side effects. So, while many people have benefited from the patches, some risks should be considered. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Unlike the standard treatments for depression, which typically include antidepressants like SSRIs and therapy, the transdermal nicotine patch offers a unique approach. Researchers are excited about this method because it uses nicotine, a new active ingredient for depression treatment, which may target different neural pathways involved in mood regulation. This patch also provides a novel delivery method, allowing for a gradual and adjustable release of nicotine through the skin, which could potentially lead to faster onset of effects and more flexible dosing. This approach could be especially beneficial for patients who haven't responded well to traditional medications.

What evidence suggests that the transdermal nicotine patch could be an effective treatment for late-life depression?

Research has shown that nicotine patches, applied to the skin, might improve mood and thinking skills in older adults with depression. In this trial, participants will be randomized to receive either the Transdermal Nicotine Patch or a Transdermal Placebo Patch. Studies have found that nicotine patches can significantly reduce depression severity, with up to 86.7% of people responding positively and 59% experiencing full relief from symptoms. This suggests that nicotine patches might enhance brain function, which could benefit those with depression later in life. Additionally, even short-term use of nicotine patches has improved mood. Overall, these findings support the potential of nicotine patches to aid older adults with depression-related cognitive issues. ^{1 2 4 6 7}

Who Is on the Research Team?

Warren Taylor

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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

Cognition: MMSE ≥ 24

Fluent in English

I am currently experiencing mild or more severe symptoms of depression.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

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]

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 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]

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 ... Results. Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8306757/

Two studies of the clinical effectiveness of the nicotine ... Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco ...

4. 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 ...

5. nature.com nature.com/articles/1395625

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

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2917405/

Adverse events associated with nicotine replacement therapy ... A pooled analysis of 12 RCTs found a statistically significant increased risk for heart palpitations and chest pains associated with NRT (OR 2.06, 95% CI, 1.51- ...

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 ...