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Nicotine-replacement therapy with use of a transdermal nicotine patch--a randomized double-blind placebo-controlled trial.

The rate of smoking was significantly reduced in volunteer subjects by providing effective nicotine replacement, self-help material, and weekly visits with a nurse for 6 weeks. Nicotine-replacement therapy with a transdermal nicotine patch (Nicolan) almost doubled the 6-week smoking-cessation rate in comparison with that in a placebo group (77% versus 39%; P = 0.002) among subjects who were smoking at least 20 cigarettes per day at baseline. Although most subjects who used the active nicotine patches had skin reactions, the reactions were primarily mild. For use of both active and placebo patches, the level of patient compliance was high. Among subjects who continued to smoke, the use of cigarettes was decreased to less than 50% of the baseline smoking level in 7 of 7 with active nicotine patches and in 15 of 19 with placebo patches. Outcomes beyond 6 weeks showed a substantial relapse rate in both groups. Thus, when nicotine-replacement therapy is provided, a need exists for concurrent behavioral intervention and training for prevention of a relapse, neither of which was part of this protocol.

Administration, Cutaneous

Dependence potential and abuse liability of nicotine replacement therapies.

Some abstinent smokers develop withdrawal symptoms when they stop using nicotine gum or when placebo is substituted; thus, physical dependence on nicotine gum does occur. Some smokers also use nicotine gum beyond the recommended period; thus, behavioral dependence on the gum occurs. Many (7-41%) smokers misuse nicotine gum by smoking cigarettes and chewing the gum concurrently. Among smokers who stop using the gum, many (35-90%) do not stop gum use by the recommended 3 months, and a substantial percentage (13-38%) persist in gum use for 1 year. Among quitters, long-term use of nicotine gum appears to be greater than that of placebo gum. If rapidity of onset and frequency of use are determinants of dependence potential, then nasal sprays and aerosols but not nicotine patches should have dependence potential. There are no reports of misuse of the gum by non-smokers; thus, the gum appears to have little if any abuse liability.

Chewing Gum

Pharmacotherapy for smoking cessation.

Nicotine dependence and the role of various pharmacotherapeutic adjuncts in the medical management of nicotine withdrawal and smoking cessation are reviewed. Nicotine has been shown to be the drug in tobacco that causes addiction. The nicotine withdrawal syndrome is primarily characterized by craving, irritability, frustration, anger, anxiety, poor concentration, restlessness, weight gain, and decreased heart rate. Pharmacotherapeutic interventions can be classified into four groups: therapy that (1) replaces nicotine, (2) antagonizes nicotine, (3) provides symptomatic treatment for nicotine withdrawal, and (4) deters smoking. Nicotine replacement therapy with nicotine polacrilex gum has had minimal effect on increasing-smoking cessation among patients seen in a general medical practice setting. It is most effective in nicotine dependent smokers when it is used concomitantly with behavioral or psychological counseling. Nicotine antagonist therapy with mecamylamine may be useful in recalcitrant cases of nicotine dependence. Clonidine, in both oral and transdermal forms, has been shown to be effective for reduction of symptoms and craving associated with smoking cessation. Research on using the tricyclic antidepressants imipramine and doxepin to promote smoking cessation by reducing withdrawal symptoms is in its preliminary phases. Lobeline, an alkaloid with effects similar to those of nicotine, is an FDA Category III drug (i.e., safe, but of unknown efficacy) and is available without prescription. Silver acetate chewing gum deters smoking by producing an unpleasant metallic taste on concomitant ingestion of the agent and tobacco. It is an FDA Category III drug and is available without prescription. Drugs used in therapy of nicotine withdrawal include nicotine replacements, nicotine antagonists, agents to lessen the symptoms of withdrawal, and smoking deterrents. None of the drugs is completely effective. Successful drug use for smoking cessation involves consideration of the psychological, as well as physiological, aspects of nicotine addiction.

Humans

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

Transdermal nicotine delivery systems are a cigarette smoking cessation aid designed to deliver nicotine into the systemic circulation via the skin. The partial replacement of plasma nicotine, which would have otherwise been obtained from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so allows the smoker to abstain from smoking more easily. The systems are available in 16- and 24-hour application regimens, and are recommended for daily use for up to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks of application of transdermal nicotine systems, compared with 4 to 21% with placebo systems. The use of concomitant behavioural therapy may increase the success of treatment, with initial abstinence rates of up to 86% reported. However, long term abstinence rates (greater than 6 months) are considerably lower with or without behavioural therapy, often falling to less than half of the initial rates. Transdermal nicotine systems have been well tolerated in clinical trials, with local irritation at the site of application being the most common adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances have also been reported. The ease of use and unobtrusive nature of the systems have resulted in a high degree of patient compliance. Thus, transdermal nicotine systems offer a convenient form of nicotine replacement therapy which are well tolerated and, due to their pharmacokinetic profile, probably have a low dependency potential. The short term abstinence rates achieved with this therapy are encouraging; however, the maintenance of abstinence in the long term is harder to achieve. Transdermal nicotine replacement therapy, therefore, represents an important advance in the difficult area of smoking cessation management.

Administration, Cutaneous

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I²=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I²=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I²=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I²=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

The physician's role in smoking cessation. A present and future agenda.

Medical views in the United States on the effects of smoking have shifted dramatically since the published evidence in 1958 established the link between smoking and fatal disease. Today's physician should be a nonsmoking role model, whose workplace both directly and indirectly teaches smoking cessation skills. Publications on smoking cessation techniques from the National Institutes of Health along with intervention tools such as patient smoking history questionnaires are available free of charge to physicians. Patient histories are critical to the intervention process, for they provide essential clues and information about which stage in cessation of smoking the patient has already reached: precontemplation, contemplation, action, and maintenance. Different approaches and techniques are required at each stage. The most important objective for the physician with a patient at the stage of contemplating quitting is to initiate a conversation leading to a directive to quit, with benefits of quitting stressed as reinforcement. Actively motivated patients committed to quit dates may need both educational and pharmacologic support; issues such as nicotine dependence and withdrawal symptoms must be addressed. Pharmacologic therapy at this time may consist of substitution of nicotine-containing gum (nicotine polacrilex) for cigarettes. Used in sufficient, regular dosages, the nicotine gum has been found to help diminish withdrawal symptoms following smoking cessation. Other drug therapies are currently under study. For now, nicotine replacement therapy (where indicated) is to be used for at least three months, the period of greatest chance of relapse. The physician should continue to encourage patients who have quit smoking to forestall relapses, while tacitly understanding that the incidence of relapse is high in first-time quitters. Hospital inpatients provide an opportunity to initiate bedside smoking cessation programs. The hope is that, in the future, hospitals will involve the entire health team in comprehensive smoking cessation programs.

Humans

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans

Affect regulation, nicotine addiction, and smoking cessation.

Numerous investigators have examined the role of negative affective states and affect regulation in the initiation and development of cigarette smoking behavior, smoking cessation, and relapse prevention. Affect regulation refers to any attempt to alleviate negative mood states by means of pharmacologic-, cognitive-, behavioral- or environmental-change methods. The psychological construct/process of affect regulation is examined in relation to (1) the initiation, development, and maintenance of the cigarette smoking habit; (2) the process of quitting smoking; and (3) the long-term maintenance of smoking abstinence versus relapse. Various psychosocial factors and physiological mechanisms are explored that have been hypothesized to be links between negative mood states, nicotine addiction, and smoking cessation. Implications for smoking cessation treatment are discussed in the areas of (1) the use of pharmacologic agents, such as clonidine, in the reduction of nicotine withdrawal symptoms; (2) nicotine replacement therapy; and (3) skills-training approaches to smoking cessation and relapse prevention.

Affect

Pharmacokinetics of nicotine and cotinine after application of two different nicotine patches under steady state conditions.

Tobacco use has resulted in major health related problems world-wide. Transdermal nicotine replacement therapy is one of the most promising strategies in smoking cessation. In the present trial the pharmacokinetic properties of two matrix patches (A and B) were characterized and compared after daily application on day 4. Predose nicotine concentrations on day 4 with patch B were higher than with patch A (12.7 +/- 9.5 ng/ml vs. 8.3 +/- 5.3 ng/ml). With patch A there was a steeper increase up to the peak level, followed by a decline gradually up to 24 h. 24 h after application predose levels were reached again, demonstrating absence of significant accumulation of nicotine. The calculated elimination half-lives of nicotine (3.4 +/- 1.8 h after patch A and 3.3 +/- 2.0 h after patch B) were longer than after i.v. application (published values range from 40 to 120 min). Under steady state cotinine concentrations remained constant.

Administration, Cutaneous

Nicotine and the central nervous system: biobehavioral effects of cigarette smoking.

The effects of nicotine, like those of other drugs with potential for abuse and dependence, are centrally mediated. The impact of nicotine on the central nervous system is neuroregulatory in nature, affecting biochemical and physiological functions in a manner that reinforces drug-taking behavior. Dose-dependent neurotransmitter and neuroendocrine effects occur as plasma nicotine levels rise when a cigarette is smoked. Circulating levels of norepinephrine and epinephrine increase, and the bioavailability of dopamine is altered as well. Among the neuroendocrine effects are release of arginine vasopressin, beta-endorphin, adrenocorticotropic hormone, and cortisol. Notably, several of these neurochemicals are psychoactive and/or known to modulate behavior. Thus, affective states or cognitive demands may be favorably modified (at least temporarily) by nicotine intake. When nicotine is inhaled, the neuroregulatory effects just described are immediately available and the reinforcing effects of the drug are maximized. On the other hand, nicotine gum and most other nicotine replacement vehicles in current use have a slower onset of action, resulting in less reinforcement value. Recent data suggest that smoking cessation rates may be optimized by tailoring the dose of nicotine replacement (for example, 2 or 5 mg of nicotine gum) to the individual degree of nicotine dependence. In view of the dynamic interactions between the neuroregulatory effects of nicotine and a host of environmental conditions, nicotine replacement therapy is best carried out in combination with behavior modification techniques.

Behavior

Tobacco, nicotine, and cannabis use and exposure in an Australian Indigenous population during pregnancy: A protocol to measure parental and foetal exposure and outcomes.

BACKGROUND: The Australian National Perinatal Data Collection collates all live and stillbirths from States and Territories in Australia. In that database, maternal cigarette smoking is noted twice (smoking <20 weeks gestation; smoking >20 weeks gestation). Cannabis use and other forms of nicotine use, for example vaping and nicotine replacement therapy, are nor reported. The 2021 report shows the rate of smoking for Australian Indigenous mothers was 42% compared with 11% for Australian non-Indigenous mothers. Evidence shows that Indigenous babies exposed to maternal smoking have a higher rate of adverse outcomes compared to non-Indigenous babies exposed to maternal smoking (S1 File). OBJECTIVES: The reasons for the differences in health outcome between Indigenous and non-Indigenous pregnancies exposed to tobacco and nicotine is unknown but will be explored in this project through a number of activities. Firstly, the patterns of parental and household tobacco, nicotine and cannabis use and exposure will be mapped during pregnancy. Secondly, a range of biological samples will be collected to enable the first determination of Australian Indigenous people's nicotine and cannabis metabolism during pregnancy; this assessment will be informed by pharmacogenomic analysis. Thirdly, the pharmacokinetic and pharmacogenomic findings will be considered against maternal, placental, foetal and neonatal outcomes. Lastly, an assessment of population health literacy and risk perception related to tobacco, nicotine and cannabis products peri-pregnancy will be undertaken. METHODS: This is a community-driven, co-designed, prospective, mixed-method observational study with regional Queensland parents expecting an Australian Indigenous baby and their close house-hold contacts during the peri-gestational period. The research utilises a multi-pronged and multi-disciplinary approach to explore interlinked objectives. RESULTS: A sample of 80 mothers expecting an Australian Indigenous baby will be recruited. This sample size will allow estimation of at least 90% sensitivity and specificity for the screening tool which maps the patterns of tobacco and nicotine use and exposure versus urinary cotinine with 95% CI within &#xb1;7% of the point estimate. The sample size required for other aspects of the research is less (pharmacokinetic and genomic n = 50, and the placental aspects n = 40), however from all 80 mothers, all samples will be collected. CONCLUSIONS: Results will be reported using the STROBE guidelines for observational studies. FORWARD: We acknowledge the Traditional Custodians, the Butchulla people, of the lands and waters upon which this research is conducted. We acknowledge their continuing connections to country and pay our respects to Elders past, present and emerging. Notation: In this document, the terms Aboriginal and Torres Strait Islander and Indigenous are used interchangeably for Australia's First Nations People. No disrespect is intended, and we acknowledge the rich cultural diversity of the groups of peoples that are the Traditional Custodians of the land with which they identify and with whom they share a connection and ancestry.

Adult

Recurrent aphthous ulcers and nicotine.

OBJECTIVE: The aim of this study was to investigate the effect of nicotine, in the form of Nicorette tablets, on aphthous ulcers in non-smoking patients. The study was prompted by the observations that smokers are less likely to suffer from mouth ulcers, that some smokers on quitting develop them, and that patients on nicotine replacement therapy are less likely to develop ulcers than those having other types of smoking cessation therapy. CLINICAL FEATURES: The three non-smoking patients who were selected for the study each had a long history of recurrent aphthous ulcers with no remissions. INTERVENTION AND OUTCOME: Each patient was given up to four 2 mg Nicorette chewing tablets per day. After one month of this regimen each patient was weaned off the tablets. In each case the ulcers healed and new ulcers did not appear during Nicorette therapy. Two of the patients relapsed when weaned off the tablets. CONCLUSIONS: This preliminary trial shows that nicotine may have a beneficial effect on aphthous ulcers. Further studies are necessary to elucidate the mechanism.

Administration, Oral

Smoke-free Europe in the year 2000: nongovernmental action (smoking cessation treatment).

Tobacco control has to be performed by following a comprehensive approach. This approach means a variety of strategies including health education and public information, smoking cessation, legislation, price policy, and taxation. It is the responsibility of the health care system to provide treatment for those who are nicotine addicted. There is now sufficient scientific background for cessation to be implemented much more than before. Cessation means offering a wide variety of techniques and methods for different target groups, and providing different organizational structures with different levels of assistance for the smoker. A diversified system of techniques to help the smoker to stop includes the following. Methods to help the already highly motivated, low-dependent smoker (mass media-assisted techniques, simple brochures, self-help techniques) Methods to help motivated, rather highly dependent smokers (e.g., nicotine replacement therapy) Basic for all the other intervention techniques are methods to create and maintain motivation (health education, public information, public education).

Europe