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Effectiveness of Extended-Duration Transdermal Nicotine Therapy: A Randomized Trial

Robert A. Schnoll, PhD; Freda Patterson, PhD; E. Paul Wileyto, PhD; Daniel F. Heitjan, PhD; Alexandra E. Shields, PhD; David A. Asch, MD; and Caryn Lerman, PhD
[+] Article and Author Information

From University of Pennsylvania, Philadelphia, Pennsylvania, and Massachusetts General Hospital, Boston, Massachusetts.


A preliminary report of the study findings was presented at the annual meeting of the Society for Research on Nicotine and Tobacco, 27 February 2008, Portland, Oregon.

Acknowledgment: The authors thank Dr. Janet Audrain-McGovern, Dr. Margaret Rukstalis, Angela Pinto, Susan Ware, Kia Kerrin, Janice Biddle, Sean Fleming, Paul Sanborn, and Susan Kerns for assisting with study implementation or manuscript preparation.

Grant Support: By a Transdisciplinary Tobacco Use Research Center Grant from the National Cancer Institute and the National Institute on Drug Abuse (P50 CA/DA84718 and P50 CA143187).

Potential Conflicts of Interest: Dr. Lerman has served as a consultant to GlaxoSmithKline, one company that manufactures the nicotine patch. She has also served as a consultant or has received research funding from AstraZeneca, Pfizer, and Novartis. Financial support for this study was not provided by an industry sponsor. Dr. Lerman had full access to the data and had full responsibility for the decision to submit for publication.

Reproducible Research Statement:Study protocol: Available from Dr. Lerman (e-mail, clerman@mail.med.upenn.edu). Statistical code: Available from Dr. Wiley (e-mail, epw@mail.med.upenn.edu). Data set: Available after 1 January 2011 from Dr. Schnoll (e-mail, schnoll@mail.med.upenn.edu).

Corresponding Author: Robert A. Schnoll, PhD, Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104; e-mail, schnoll@mail.med.upenn.edu.

Current Author Addresses: Drs. Schnoll, Patterson, Wileyto, and Lerman: Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA 19104.

Dr. Heitjan: Department of Biostatistics and Epidemiology, University of Pennsylvania, 622 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104.

Dr. Shields: Massachusetts General Hospital, 50 Staniford Street, Boston, MA 02114.

Dr. Asch: Leonard Davis Institute of Health Economics, University of Pennsylvania, 3641 Locust Walk, Philadelphia, PA 19104.

Author Contributions: Conception and design: E.P. Wileyto, D.F. Heitjan, C. Lerman.

Analysis and interpretation of the data: R.A. Schnoll, E.P. Wileyto, D.F. Heitjan, A.E. Shields, D.A. Asch, C. Lerman.

Drafting of the article: R.A. Schnoll, F. Patterson, E.P. Wileyto, D.F. Heitjan, A.E. Shields, C. Lerman.

Critical revision of the article for important intellectual content: R.A. Schnoll, E.P. Wileyto, D.F. Heitjan, A.E. Shields, D.A. Asch, C. Lerman.

Final approval of the article: R.A. Schnoll, F. Patterson, E.P. Wileyto, D.F. Heitjan, A.E. Shields, D.A. Asch, C. Lerman.

Statistical expertise: E.P. Wileyto, D.F. Heitjan.

Obtaining of funding: C. Lerman.

Administrative, technical, or logistic support: F. Patterson.

Collection and assembly of data: F. Patterson.


Ann Intern Med. 2010;152(3):144-151. doi:10.7326/0003-4819-152-3-201002020-00005
Text Size: A A A

Background: Tobacco dependence is a chronic, relapsing condition that may require extended treatment.

Objective: To assess whether extended-duration transdermal nicotine therapy increases abstinence from tobacco more than standard-duration therapy in adult smokers.

Design: Parallel randomized, placebo-controlled trial from September 2004 to February 2008. Participants and all research personnel except the database manager were blinded to randomization. (ClinicalTrials.gov registration number: NCT00364156)

Setting: Academic center.

Participants: 568 adult smokers.

Intervention: In an unstratified small block–randomization scheme, participants were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks).

Measurements: The primary outcome was biochemically confirmed point-prevalence abstinence at weeks 24 and 52. Secondary outcomes were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, and side effects and adherence.

Results: At week 24, extended therapy produced higher rates of point-prevalence abstinence (31.6% vs. 20.3%; odds ratio, 1.81 [95% CI, 1.23 to 2.66]; P = 0.002), prolonged abstinence (41.5% vs. 26.9%; odds ratio, 1.97 [CI, 1.38 to 2.82]; P = 0.001), and continuous abstinence (19.2% vs. 12.6%; odds ratio, 1.64 [CI, 1.04 to 2.60]; P = 0.032) versus standard therapy. Extended therapy reduced the risk for lapse (hazard ratio, 0.77 [CI, 0.63 to 0.95]; P = 0.013) and increased the chances of recovery from lapses (hazard ratio, 1.47 [CI, 1.17 to 1.84]; P = 0.001). Time to relapse was slower with extended versus standard therapy (hazard ratio, 0.50 [CI, 0.35 to 0.73]; P < 0.001). At week 52, extended therapy produced higher quit rates for prolonged abstinence only (P = 0.027). No differences in side effects and adverse events between groups were found at the extended-treatment assessment.

Limitation: The generalizability of the findings may be limited because participants were smokers without medical comorbid conditions who were seeking treatment, and differences in adherence across treatment groups were detected.

Conclusion: Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy.

Primary Funding Source: National Institutes of Health.

Figures

Grahic Jump Location
Figure 1.
Study flow diagram.

CO = carbon monoxide.

* A list of the reasons for participant ineligibility can be provided on request. Inclusion and exclusion criteria listed in the text were identical for telephone and in-person eligibility assessments.

† Indicates participants included in the intention-to-treat analysis.

‡ One participant became ineligible after being randomly assigned and before receiving treatment.

§ Six participants became ineligible after being randomly assigned and before receiving treatment.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Time to relapse at week 52, by treatment group.

The model controlled for age (HR, 1.00 [95% CI, 0.99 to 1.01]; P = 0.65), sex (HR, 0.96 [CI, 0.77 to 1.19]; P = 0.69), and level of nicotine dependence. Nicotine dependence level predicted relapse from weeks 0 to 8 (HR, 1.83 [CI, 1.35 to 2.48]; P < 0.001) but not from weeks 9 to 24 (HR, 0.91 [CI, 0.61 to 1.36]; P = 0.65) or weeks 25 to 52 (HR, 1.04 [CI, 0.60 to 1.70]; P = 0.90). The HRs were stable and uniform over the intervals (P = 0.80). A residual decline in abstinence after 24 weeks occurred, but the decline was statistically equivalent across treatment groups. HR = hazard ratio; μR = restricted mean number of weeks to relapse (included censored observation times).

* Participants at risk for relapse.

Grahic Jump Location

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Comments

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2 of 282 extended patch users quit 1 year
Posted on February 7, 2010
John R. Polito
WhyQuit.com
Conflict of Interest: None Declared

While benefit at 24 weeks, Schnoll and colleagues report nearly identical one-year point prevalence smoking cessation rates following 24 weeks of nicotine patch use versus the standard 8 weeks. They ignore long-term outcome in suggesting that their extended patch study "demonstrates the benefits of extended duration therapy with transdermal nicotine(1)." They arrive at this conclusion when only 2 of 282 extended patch quitters were able to stop smoking for the entire year, an appalling one-year continuous cessation rate of 0.7%. Contrary to suggesting extended use benefit, eight week patch users actually had a 30% higher rate of 1.0%, reflecting 3 of 286 participants able to quit smoking for a full year (1).

The authors ignore the fact that while historic one-year unaided continuous smoking cessation rates range from 3 to 11%[2], that the generally accepted rate is 5%, a minimum 7-fold advantage over this study's 0.7% finding.

This study exposes the reality that more than 200 placebo-controlled nicotine replacement studies were not about arresting chemical dependency upon nicotine but about ending a single form of delivery, smoking it. This study supports the contention that the human brain cannot down-regulate a4b2-type nicotinic receptor counts nor re-sensitize them while nicotine continues to arrive (3).

It evidences the neuro-chemical reality that using nicotine to aid nicotine addicts in quitting makes about as much sense as giving alcohol to alcoholics. Quality nicotine cessation research involves acceptance of three key factors: (1) that no placebo-controlled trial has yet been blind as claimed, that it is impossible to blind smokers with lengthy quitting histories as to the presence or absence of full-blown withdrawal, as that they are experts at recognizing it[4]; (2) teaching total respect for the "Law of Addiction," that just one puff or hit and up to 50% of the brain's a4b2-type receptors will become occupied by nicotine,(5) that while the smoker may walk away from relapse thinking they have gotten away with it, that their brain will soon be begging for more;(6) and, (3) that two weeks of intense abrupt cessation counseling and support (12-14 hours) are key to dramatically enhancing long-term nicotine cessation rates.

Schnoll and colleagues abandon the goal of nicotine cessation, impliedly suggesting that success can be claimed by keeping smokers dependent upon NRT for life. They propose this non-cessation solution knowing that even by their own data, which employs a quitting definition that's extremely forgiving of relapse, that roughly 70% of extended patch users had relapsed prior to 24 weeks.

Before abandoning nicotine cessation we need to design and execute studies where it's the sole objective. While smoking morbidity and mortality are compelling motivations, life isn't about how we eventually die but life's quality today. Nicotine addiction is about living a lie, that endless chemical servitude to nicotine's two-hour half-life is more important than life itself. It's time to destroy needless anxiety generating fears by attacking the lie itself. Smokers do not smoke because of flavor, boredom, aroma, pleasure or stress. They do so because they must, because a rising tide of insula routed anxieties begin to hurt when they don't.

References

[1] Schnoll RA et al, Effectiveness of Extended-Duration Transdermal Nicotine Therapy: A Randomized Trial, Ann Intern Med 2010 152:144-151.

[2] Gritz ER et al, Unaided Smoking Cessation, Great American Smokeout and New Year's Day Quitters, Journal of Psychosocial Oncology, Volume 6, Issue 3; 4 March 1989, pages 217-234.

[3] Ortells MO, Barrantes GE, Tobacco addiction: A biochemical model of nicotine dependence, Med Hypotheses, 2009 Dec 2. [Epub ahead of print].

[4] Polito JR, Smoking Cessation Trials, CMAJ, November 4, 2008; 179 (10); and Mooney M, et al, The blind spot in the nicotine replacement therapy literature: Assessment of the doubleblind in clinical trials, Addict Behav., 2004 June;29(4):673-684.

[5] Brody AL et al,Cigarette smoking saturates brain alpha 4 beta 2 nicotinic acetylcholine receptors, Archives of General Psychiatry, August 2006, Volume 63(8), Pages 907-915.

[6] Brandon, TH et al, Postcessation cigarette use: the process of relapse, Addictive Behaviors, 1990; 15(2), pages 105-114; and Borland R, Slip-ups and relapse in attempts to quit smoking, Addictive Behaviors, 1990, Volume 15(3), Pages 235-245.

Conflict of Interest:

Director WhyQuit.com, an abrupt nicotine cessation forum and author of Freedom from Nicotine - The Journey Home.

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Summary for Patients

Extended Nicotine Treatment for Long-Term Smokers

The summary below is from the full report titled “Effectiveness of Extended-Duration Trans-dermal Nicotine Therapy. A Randomized Trial.” It is in the 2 February 2010 issue of Annals of Internal Medicine (volume 152, pages 144-151). The authors are R.A. Schnoll, F. Patterson, E.P. Wileyto, D.F. Heitjan, A.E. Shields, D.A. Asch, and C. Lerman.

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