Overseen ByAmy Janes, Ph.D.
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
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.
12345Is 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.
35678How 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.
13459Eligibility 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
+10 more
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
+16 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm 2: Nicotine PatchExperimental Treatment1 Intervention
Nicotine Patch + Placebo Pill
Group II: Arm 1: PlaceboPlacebo Group1 Intervention
Placebo patch + Placebo Pill
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institute on Drug AbuseBaltimore, MD
Loading ...
Who Is Running the Clinical Trial?
National Institute on Drug Abuse (NIDA)Lead Sponsor
References
The effects of transdermal nicotine therapy for smoking cessation on depressive symptoms in patients with major depression. [2015]This study examines the effects of transdermal nicotine patches for smoking cessation on depressive and withdrawal symptoms among 38 non-medicated subjects with Major Depressive Disorder. The study was conducted over a 29-day period, which included a 7 day baseline phase, a 14 day treatment phase, and an 8 day placebo phase. During the treatment phase subjects received either active nicotine patches (N = 18) or placebo patches (N = 20) that were administered in a randomized, double-blind fashion. The target quit date (TQD) was day 8. Significantly, more subjects in the placebo group than in the nicotine group resumed smoking following the TQD (50% vs. 22%). There was little evidence for effects of active nicotine patches on measures of mood (HRSD, BDI, POMS) or withdrawal symptoms among subjects that remained abstinent throughout the study (N = 24). Those who resumed smoking had more severe withdrawal symptoms than those who remained abstinent. One patient in the placebo group (n = 20) became more depressed after 2 weeks of abstinence. None of the patients in the nicotine group (n = 18) became more depressed.
The effect of nicotine patch therapy on depression in nonsmokers: a preliminary study. [2019]Prior uncontrolled studies of nonsmokers with major depressive disorder (MDD) indicate rapid reduction in depressive symptoms with nicotine patch therapy. This randomized, double-blind, placebo-controlled pilot study examined the effect of nicotine patch therapy on depressive symptoms in non-medicated nonsmokers with current MDD. Due to recruitment difficulties, only 7 were enrolled and of these 6 (5 females, 1 male) completed the study. Participants received either placebo (n = 4) or active (n = 2) patch therapy for 8 days. They completed daily clinic visits during patch therapy and a final visit on Day 12. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HRSD). The mean change in HRSD scores of all participants decreased (p = 0.021) from baseline by Day 1 of patch use. Similar decreases in HRSD scores were observed for placebo and active patch groups. Among the placebo participants, the mean HRSD score decreased (p = 0.038) by Day 2. The study needs replication with a larger sample and utilizing novel recruitment strategies.
Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone. [2019]To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation.
New medications for nicotine dependence treatment. [2019]For several years, nicotine replacement therapy (nicotine gum, patches, and nasal spray) has been the mainstay for the treatment of nicotine dependence. The nicotine vapor inhaler is a new pharmacological adjunct shown to be effective in placebo-controlled trials. It delivers a vaporized form of nicotine to the oral mucosa. Bupropion sustained release (SR) is the first non-nicotine pharmacological treatment approved for smoking cessation and is thought to be effective because of its dopaminergic activity on the pleasure and reward pathways in the mesolimbic system and nucleus accumbens. Though few studies have been reported, there is pharmacological rationale to use combined pharmacotherapies for the treatment of nicotine dependence. While there are a limited number of reported studies with mixed findings using higher than the standard nicotine patch dose, use of higher doses of nicotine patch therapy (i.e., more than one patch at a time) may be appropriate for smokers who previously failed single dose patch therapy or in those whose nicotine withdrawal symptoms were not adequately relieved with standard therapy. The concept of therapeutic drug monitoring can be applied to nicotine replacement therapy. A new product, a sublingual nicotine tablet, has shown efficacy in a double-blind placebo-controlled trial and will likely be approved in the future. The anti-hypertensive, mecamylamine, has been found to have efficacy for smoking cessation in a small trial. Nicotine and mecamylamine both occupy receptors that would otherwise be acted upon by nicotine from cigarettes, thus, when administered in combination, would be expected to occupy more receptors than either drug alone, thereby attenuating smoking reward and facilitating extinction of the smoking behavior. Pivotal trials of this combination are underway. Remaining questions include: (1) what is the optimal dose and duration of treatment using nicotine replacement therapy? (2) What is the optimal duration of treatment using bupropion? (3) What are the best combination treatments and which smokers are best suited for combination treatment? (4) Will other similar pharmacological agents with dopaminergic/noradrenergic activity have efficacy similar to bupropion?
The effects of fluoxetine combined with nicotine inhalers in smoking cessation--a randomized trial. [2019]Nicotine replacement therapy (NRT) is an established aid in stopping smoking, while the role of antidepressants remains uncertain. Antidepressants added to NRT might improve abstinence rates. Our aim was to determine the efficacy of nicotine inhaler and fluoxetine vs. nicotine inhaler and placebo in attempts to quit smoking.
Neuropsychiatric Safety and Efficacy of Varenicline, Bupropion, and Nicotine Patch in Smokers With Psychotic, Anxiety, and Mood Disorders in the EAGLES Trial. [2020]Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest.
[A double-blind trial of nicotine patches in smoking cessation]. [2015]The use of nicotine chewing gum combined with psychological support improves the success rate in stopping smoking. We studied the safety and efficacy of a transdermal nicotine patch in stopping smoking. We conducted a double-blind randomized study comparing the effect of a 16-hour nicotine patch (15 +/- 3.5 mg of nicotine in 16 hours) with those of a placebo patch. Of the 289 smokers (207 women and 82 men) enrolled in the study, 145 were treated with nicotine patches and 144 with placebo patches for 16 weeks. The rates of sustained abstinence were significantly better with active treatment than with the placebo: 53, 41, 24 and 17% of those in the nicotine-patch group were abstinent after 6, 12, 26, and 52 weeks, respectively, as compared with 17, 10, 5 and 4% of those in the placebo-patch group (p less than 0.0001). Only two subjects with the nicotine patch and one with the placebo patch withdrew from the study because of side effects. The nicotine skin patch proved to be safe and effective, as demonstrated by a higher rate of abstinence than with the placebo.
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]Nicotine replacement therapy (NRT) has been used in the treatment of tobacco dependence for over three decades. Whilst the choice of NRT was limited early on, in the last ten years there has been substantial increase in the number of nicotine delivery devices that have become available. This article briefly summarises existing forms of NRT, evidence of their efficacy and use, and reviews the rationale for the development of novel products delivering nicotine via buccal, transdermal or pulmonary routes (including nicotine mouth spray, nicotine films, advanced nicotine inhalers and electronic cigarettes). It presents available evidence on the efficacy, tolerability and abuse potential of these products, with a focus on their advantages as well as disadvantages compared with established forms of NRT for use as an aid to both smoking cessation as well as harm reduction.
Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study. [2022]There is evidence for nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects, presumably mediated through stimulation of nicotinic acetylcholine receptor systems. We compared the nicotinic antagonist, mecamylamine hydrochloride (MEC), with placebo as an augmentation strategy for patients with MDD who were refractory to selective serotonin reuptake inhibitor (SSRI) treatment.