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

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 thinking skills in older adults with depression. The focus is on enhancing cognitive control, which influences tasks like memory and emotional regulation and is often impaired in late-life depression. Participants must have completed a previous study phase and been diagnosed with major depressive disorder while on specific antidepressants. They should not have recently used tobacco or nicotine or undergone therapies like electroconvulsive therapy. The trial requires wearing a nicotine patch daily for up to 15 weeks. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that the Transdermal Nicotine Patch is likely to be safe for humans?

Research has shown that nicotine patches, applied to the skin, may improve mood and cognitive function in individuals with late-life depression. In past studies, many participants experienced improvement in their depression symptoms. One study found that 86.7% of participants responded positively, with 53.3% experiencing significant symptom reduction or remission. Another study reported a 76% positive response rate, with 59% experiencing significant symptom relief.

While these results are encouraging, potential side effects should be considered. A review of several studies found that nicotine patches might increase the risk of heart palpitations and chest pain, occurring more frequently than expected.

Overall, the nicotine patch is generally well-tolerated, but some risks exist. Prospective trial participants should discuss these potential side effects with the research team and their doctor. ^{1 2 3 4 5}

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

Unlike the standard treatments for depression, which often include medications like SSRIs or SNRIs, the transdermal nicotine patch offers a unique approach by using nicotine as an active ingredient. Researchers are interested in this treatment because nicotine may modulate certain neurotransmitter systems differently than traditional antidepressants, potentially offering relief for those who haven't responded well to current options. Additionally, the patch's transdermal delivery system provides a steady absorption of nicotine, which could minimize side effects compared to oral medications. This innovative method gives researchers hope for more tailored and effective depression treatments.

What evidence suggests that the Transdermal Nicotine Patch might be an effective treatment for late-life depression?

Research has shown that nicotine patches, applied to the skin, might improve mood and thinking in people with late-life depression. In small studies where participants knew they were using the patches, up to 86.7% felt better, and 53.3% experienced a significant reduction in depression symptoms. Another study found that 76% of participants felt better, with 59% experiencing significant symptom relief. These findings suggest that nicotine patches might enhance brain functions related to mood and thinking, often affected in late-life depression. This trial will assess the effectiveness of the Transdermal Nicotine Patch, worn daily for 12-15 weeks, as a potential option for those who do not respond well to regular antidepressants. ^{1 2 4 6 7}

Who Is on the Research Team?

Warren D Taylor

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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 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 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 ...