Combined Use of Nicotine Patch and Gum in Smoking Cessation: A Placebo-Controlled Clinical Trial

doi:10.1006/pmed.1995.1006

Preventive Medicine

Volume 24, Issue 1, January 1995, Pages 41-47

https://doi.org/10.1006/pmed.1995.1006 Get rights and content

Abstract

Background. Smoking is considered as an addiction to nicotine for most subjects consuming 10 cigarettes or more per day. Hence, nicotine replacement therapy by way of gum, patch, or spray has been advocated. The rationale of this study is to evaluate the possible beneficial effects of adding nicotine gum to the routine of subjects using the nicotine patch. The effect of the nicotine patch against the placebo, both groups receiving placebo nicotine gum, has also been assessed. Methods. Healthy subjects (374) were randomized at their work-setting in a 1-year double-blind placebo-controlled trial: 149 subjects to active nicotine patch + active gum (group 1), 150 to active nicotine patch + placebo gum (group 2), and 75 to placebo patch + gum (group 3). Treatment duration was 12 weeks with a 16-hr transdermal patch of 15 mg, followed by a 6 + B-weeks weaning period on respectively 10 and 5 mg patches. Gum use was not restricted during the first 6 months, with recommendations to use at least four pieces a day. A strict definition of smoking abstinence was used in this study, which did not allow smoking any cigarette after Week 1. Nonsmoking status at each visit, as reported by the subjects, was verified by CO below 10 ppm in expired air. Results. Abstinence rates in group 1 against group 2 were 34.2 and 22.7% (P = 0.027) at 12 weeks, 27.5 and 15.3% (P = 0.010) at 24 weeks, and 18.1 and 12.7% (P = 0.191) at 52 weeks. In group 3, abstinence rates were 17.3, 14.7, and 13.3% respectively at 12, 24, and 52 weeks. Using logistic regression with adjustment for six baseline covariates, odds ratios for abstinence (with 95% CI) were computed. For group 1/group 2, OR at 12, 24, and 52 weeks were 1.72 (1.03-2.94) (P = 0.039), 2.04 (1.14-3.57) (P = 0.018), and 1.47 (0.76-2.76) (P = 0.125). No significant differences in OR were observed when comparing groups 2 and 3. Time to relapse is significantly longer in group 1 as compared to that of group 2 (P = 0.041), whereas no significant differences between groups 2 and 3 were observed. No significant differences between the three groups in systemic and local adverse drug events were observed. Conclusion. Adding active gum use to active patch use in subjects smoking 10 cigarettes or more a day increased abstinence rates, which are statistically significant up to 24 weeks.

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This report reviews the literature on cigarette smoking published in Preventive Medicine over the past 50 years. The goal is twofold. First, to acknowledge the 50th anniversary of Preventive Medicine and its role in disseminating research on cigarette smoking by providing an abridged summary of smoking research published in the journal from inception through June 23, 2022. Second, to review experimental reports to identify contributions to innovations in tobacco control and regulatory efforts to reduce cigarette smoking. We searched PubMed using the search terms cigarette/cigarettes, tobacco products, smoking, smoking cessation, Preventive Medicine. Titles and abstracts were reviewed in duplicate, excluding reports not addressing cigarette smoking. Included reports were categorized by study type (original study, commentary, review). Experimental articles were assessed for impact using iCite, a National Institutes of Health web application that provides bibliometric information for articles in defined topic areas. The review identified 1181 articles on cigarette smoking: 1018 original studies (86.2%), 107 literature reviews (9.1%), and 56 commentaries (4.7%); 166 of the 1018 original studies (16%) were experimental reports. In the iCite analysis these 166 experimental articles received 6366 total citations, a mean (standard error) citation rate/article of 38.35 (±3.21) and mean relative citation ratio of 1.85 (±0.17) which is at the 73rd percentile for NIH-funded field- and time-normalized reports. Overall, this review demonstrates an ongoing and impactful contribution of Preventive Medicine to efforts to reduce cigarette smoking, the most preventable cause of premature death.
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Smoking is the leading cause of morbidity and mortality in different non-communicable diseases, and cessation leads to immense health benefits. The present network meta-analysis has been conducted to evaluate and compare the effects of available pharmacological interventions for smoking cessation in adults. A standard meta-analysis protocol was developed and after performing a comprehensive literature search on MEDLINE/PubMed, Cochrane databases, and International Clinical Trials Registry Platform, reviewers extracted data from 97 randomized controlled trials. PRISMA guidelines were followed in data extraction, analysis and reporting of findings. Random effects Bayesian network meta-analysis was done to pool the effects across the interventions. Network graph was built, and for closed triangles in the network graph, node splitting analysis was performed. The primary outcome measure was self-reported biochemically verified smoking abstinence at six months. The number of participants achieving continuous abstinence was reported. Data for the number of participants reporting at least one adverse event was also extracted, if available. Combination of nicotine receptor agonist and nicotine replacement therapy had a significant odd of 4.4 (95%CrI:2.2–8.7), bupropion and nicotine receptor agonist 4.0 (95%CrI:2.1–7.7), bupropion and nicotine replacement therapy 3.8 (95%CrI:2.3–6.2), combination nicotine replacement therapy has an odd of 2.6 (95%CrI:1.8–3.8), and nicotine receptor agonist had a significant odd of 2.7 (95%CrI:2.3–3.2) when compared to placebo (moderate quality of evidence) for continuous abstinence at 6 months. When compared with behavioural therapy, the odds ratio of interventions was not statistically significant. Combination of nicotine receptor agonist and nicotine replacement therapy has the highest probability of being the best treatment for abstinence from smoking.
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Since the absorption of nicotine is slower from NRTs than cigarettes, NRTs are less likely to cause dependence/addiction while still reaching sufficient concentrations to alleviate withdrawal symptoms (Henningfield and Keenan, 1993; Benowitz, 2008). Studies and meta-analyses have demonstrated that combination NRT improves abstinence rates with a similar incidence of adverse effects compared to monotherapy (Sweeney et al., 2001; Stead et al., 2012; Kornitzer et al., 1995; Cooney et al., 2009; Bohadana et al., 2000; Schlam et al., 2016; Baker et al., 2016; Piper et al., 2009; Smith et al., 2009). Dosing strategies of combination NRT, which are summarized in Table 1, vary between studies (Sweeney et al., 2001; Stead et al., 2012; Kornitzer et al., 1995; Cooney et al., 2009; Bohadana et al., 2000; Schlam et al., 2016; Baker et al., 2016; Piper et al., 2009; Smith et al., 2009).
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Combination therapy for tobacco dependence is becoming a standard of care. We sought to compare benefits and adverse events for combination therapy versus monotherapy for smokers in The Smokers' Health Project.
This secondary data analysis was derived from adult smokers (n = 198) who initially smoked 15 or more cigarettes per day and participated in The Smokers' Health Project. Participants were grouped as taking 1 medication or 2 concurrent medications for tobacco dependence for 1 year over the 2-year study period. Adverse events were compared between medication groups using chi-square tests. Crude and adjusted odds ratios were calculated for cessation at 6, 12, 18, and 24 months using logistic regression.
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To evaluate the performance of switchable carbon nanotubes (CNT) membrane devices for transdermal nicotine delivery, we have developed an in-vitro microdialysis method that allow us to detect variable transdermal fluxes of nicotine through CNT devices and can be applied directly to in-vivo studies. Microdialysis membranes were placed beneath the porcine skin and its nicotine levels increased 6-8 times when the CNT membrane on skin was turned from OFF to ON state by application of bias. Fluxes in the ON state were approximately 3 times that of commercial nicotine patches and switching times were less than two hours, thus suggesting the improved therapeutic potential of our device. Blue tooth enabled CNT devices that can be programmed by smartphone and coupled with remote counseling application for enhanced smoking cessation treatments.
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2016, American Journal of Preventive Medicine
Citation Excerpt :
The database search yielded 14,998 records, with two records identified from other sources (Figure 1). After removing duplicates and screening titles and abstracts, 587 articles underwent full-text review, of which 123 met the predefined inclusion criteria (60,774 participants).13–135 These trials were conducted primarily in the general population (93 trials), and most trials recruited participants from North America, Europe, Australia/New Zealand, or some combination of these regions (117 trials).
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The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability.
Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

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Regular ArticleCombined Use of Nicotine Patch and Gum in Smoking Cessation: A Placebo-Controlled Clinical Trial

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Regular Article
Combined Use of Nicotine Patch and Gum in Smoking Cessation: A Placebo-Controlled Clinical Trial