Safety and Efficacy of the Nicotine Patch and Gum for the Treatment of Adolescent Tobacco Addiction Eric T. Moolchan, MD; Miqun L. Robinson, MD, PhD; Monique Ernst, MD, PhD; Jean Lud Cadet, MD; Wallace B. Pickworth, PhD; Stephen J. Heishman, PhD; and Jennifer R. Schroeder, PhD ABSTRACT. Objectives. To determine the safety and cantly associated with treatment group. Mean smoking efficacy of the nicotine patch and gum for adolescents rates, but not CO or thiocyanate concentrations, de- who want to quit smoking. creased significantly in all 3 arms but not as a function of Design. Double-blind, double-dummy, randomized, treatment group. 3-arm trial with a nicotine patch (21 mg), nicotine gum (2 Conclusions. Nicotine patch therapy combined with and 4 mg), or a placebo patch and gum; all participants cognitive-behavioral intervention was effective, com- received cognitive-behavioral group therapy. pared with placebo, for treatment of tobacco dependence Setting. Inner-city, outpatient clinic on the East Coast. among adolescent smokers. Decreases in the numbers of Subjects. Thirteen- to 17-year-old adolescents who cigarettes smoked appeared to be offset by compensatory smoked >10 cigarettes per day (CPD), scored >5onthe smoking. Additional study of nicotine gum, with en- Fagerstro¨m Test of Nicotine Dependence, and were mo- hanced instructional support, is needed to assess its ef- tivated to quit smoking. ficacy among adolescent smokers. Pediatrics 2005; Intervention. Twelve weeks of nicotine patch or gum 115:e407–e414. URL: www.pediatrics.org/cgi/doi/10.1542/ therapy with cognitive-behavioral therapy, with a fol- peds.2004-1894; treatment, adolescent, tobacco, nicotine low-up visit at 6 months (3 months after the end of patch, nicotine gum, cessation, smoking reduction. treatment). Main Outcome Measures. Safety assessed on the ba- sis of adverse event reports for all 3 groups, prolonged ABBREVIATIONS. CPD, cigarettes per day; NRT, nicotine re- abstinence, assessed through self-report and verified placement therapy; FTND, Fagerstro¨m Test of Nicotine Depen- with exhaled carbon monoxide (CO) levels of <6 ppm, in dence; CO, carbon monoxide; IDR, incidence density ratio; CI, intent-to-treat analyses, and smoking reduction (CPD confidence interval; OR, odds ratio. and thiocyanate concentrations) among trial completers. Results. A total of 120 participants were randomized fter having peaked in the late 1990s, smoking :white, 70% female; age: 15.2 ؎ 1.33 years; smoking 72%) CPD; Fagerstro¨m Test of Nicotine Depen- prevalence among adolescents declined 8.56 ؎ 18.8 -dence score: 7.04 ؎ 1.29) from 1999 to 2003. Participants Aslightly, although remaining high. Percent started smoking at 11.2 ؎ 1.98 years of age and had been ages of eighth-, 10th-, and 12th-graders who reported ,smoking daily for 2.66 ؎ 1.56 years; 75% had at least 1 having smoked in the past 30 days were 10.2% current psychiatric diagnosis. Mean compliance across 16.7%, and 24.4%, respectively, in 2003.1 More im- groups was higher for the patch (mean: 78.4–82.8%) than portantly, tobacco addiction develops among adoles- for the gum (mean: 38.5–50.7%). Both the patch and gum cent smokers, and they experience withdrawal were well tolerated, and adverse events were similar to symptoms similar to those of adult smokers when those reported in adult trials. Changes in mean saliva they try to abstain from smoking.2 A large propor- cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all ran- tion of adolescent smokers have tried unsuccessfully domized participants showed CO-confirmed prolonged to stop smoking at least once, most frequently with abstinence rates of 18% for the active-patch group, 6.5% acute abstinence (“cold turkey”) methods,3 and for the active-gum group, and 2.5% for the placebo group; many desire treatment to help with cessation.4 Most the difference between the active-patch and placebo arms adolescents with established smoking habits con- was statistically significant. There was no significant tinue to smoke as adults and incur both short-term effect of patch versus gum or gum versus placebo on and long-term health consequences, including pre- cessation outcomes. Abstinence rates at the 3-month fol- mature death.5 Therefore, safe and effective smoking low-up assessment were sustained but were not signifi- cessation interventions for adolescent smokers are critically needed. From the Teen Tobacco Addiction Research Clinic, Clinical Pharmacology Although several informative reviews of the ado- and Therapeutics Research Branch, National Institute on Drug Abuse, Bal- lescent smoking-cessation literature have been pub- timore, Maryland. lished in recent years, one challenge remains, Accepted for publication Nov 9, 2004. doi:10.1542/peds.2004-1894 namely, how best to tailor the setting and modalities 6–8 No conflict of interest declared. for cessation interventions for youths. Various Reprint requests to (E.T.M.) Teen Tobacco Addiction Research Clinic, Clin- counseling and behavioral, classroom-based ap- ical Pharmacology and Therapeutics Research Branch, National Institute on proaches have included infrequent and low-level Drug Abuse, Intramural Research Program, 5500 Nathan Shock Dr, Balti- more, MD 21224. E-mail: [email protected] smokers with more intense smokers, with some PEDIATRICS (ISSN 0031 4005). Copyright © 2005 by the American Acad- yielding encouraging short-term quit rates of 30 to emy of Pediatrics. 50%.9,10 Although advocated by expert opinion in a www.pediatrics.org/cgi/doi/10.1542/peds.2004-1894Downloaded from www.aappublications.org/news by guestPEDIATRICS on October 1, Vol. 2021 115 No. 4 April 2005 e407 clinical practice guideline,11 very few pharmacologic ment could produce a substantial reduction in smok- interventions have been evaluated for treating de- ing rates among trial-completers. pendent teenage smokers. In open-label trials of the nicotine patch in combination with group counseling METHODS support, abstinence rates remained very low (4.5– Sample 12,13 ϭ 11.5%). A small-sample (N 16), open-label, bu- This study was approved by the National Institute on Drug propion study reported an abstinence rate of 31% Abuse institutional review board and was conducted in Baltimore, after 4 weeks of treatment.14 Two randomized, ado- Maryland. Outreach and recruitment were performed from Sep- tember 1999 to September 2003, through various media (print, lescent, patch trials have been reported. In the first, audiovisual, and electronic) advertisements and through various participants were randomized to the patch or pla- community channels, such as schools and churches. Adolescent cebo, in combination with intense cognitive-behav- smokers desiring to quit were encouraged to call for a structured ioral and contingency management therapies to re- telephone interview, to determine their initial preeligibility. Call- inforce tobacco abstinence. Cessation rates reached ers who reported major physical health problems or untreated acute psychiatric problems were excluded. Only participants who 18% at 3 months, but no significant treatment effect were able to discuss their smoking with their parent/guardian, was observed.15 In the other trial, teen smokers were were motivated to quit (Ͼ5 on a 10-point integer scale), and were assigned randomly to either patch plus bupropion or planning to remain in the area for the duration of the trial were patch plus placebo, with weekly group skills train- invited for on-site screening. Final eligibility was determined after an on-site history record- ing. Abstinence rates measured at weeks 10 and 26 ing, physical examination, and basic laboratory screening. Ado- were 23% and 8% for the patch plus bupropion lescents 13 through 17 years of age who were in general good group and 28% and 7% for the patch plus placebo health, had smoked Ն10 CPD for Ն6 months, had a minimal score group, respectively.16 Although no treatment effect of 5 on the Fagerstro¨m Test of Nicotine Dependence (FTND), and were motivated to stop smoking were eligible to participate. Preg- was observed, these cessation rates were encourag- nancy, lactation, chronic skin conditions, use of other tobacco ing. products, and current use (within the past 30 days) of medications Relatively low abstinence rates in previous treat- for smoking cessation (eg, NRT or bupropion) were reasons for ment trials with addicted adolescent smokers exclusion. Drug or alcohol dependence other than nicotine and current mania, psychosis, and acute depression, according to the prompted us to evaluate biochemically verified re- Diagnostic Interview of Children and Adolescents,28 which was duced smoking as a treatment outcome variable. based on the Diagnostic and Statistical Manual of Mental Disorders, Treatment-generated reductions in smoking rates Fourth Edition, were also exclusion criteria. However, candidates among adults have been reported with pharmaco- taking psychotropic medications not prescribed for smoking ces- logic methods17–19 and demonstrate the potential for sation were included in the trial. 20,21 deferred quitting. Despite limited effects on ces- Procedures 12,13 sation in the open-label youth trials, transdermal Adolescents who qualified through a 10- to 15-minute tele- nicotine therapy was associated with significant self- phone screening were invited, with a parent or guardian, to an reported decreases in cigarette consumption. This orientation meeting in which an overview of the study and clinic