Long-term Nicotine Replacement Therapy: A Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Fix  BV, Hyland  A, Rivard  C,  et al.  Usage patterns of stop smoking medications in Australia, Canada, the United Kingdom, and the United States: findings from the 2006-2008 International Tobacco Control (ITC) Four Country Survey.  Int J Environ Res Public Health. 2011;8(1):222-233.PubMedGoogle ScholarCrossref
Kasza  KA, Hyland  AJ, Borland  R,  et al.  Effectiveness of stop-smoking medications: findings from the International Tobacco Control (ITC) Four Country Survey.  Addiction. 2013;108(1):193-202.PubMedGoogle ScholarCrossref
Shiffman  S, Brockwell  SE, Pillitteri  JL, Gitchell  JG.  Use of smoking-cessation treatments in the United States.  Am J Prev Med. 2008;34(2):102-111.PubMedGoogle ScholarCrossref
Fiore  MC, Jaen  CR, Baker  TB,  et al.  Treating Tobacco Use and Dependence: 2008 Update. Rockville, MD: US Public Health Service; 2008. US Public Health Service Clinical Practice Guideline.
Stead  LF, Perera  R, Bullen  C,  et al.  Nicotine replacement therapy for smoking cessation.  Cochrane Database Syst Rev. 2012;11:CD000146.PubMedGoogle Scholar
Carpenter  MJ, Jardin  BF, Burris  JL,  et al.  Clinical strategies to enhance the efficacy of nicotine replacement therapy for smoking cessation: a review of the literature.  Drugs. 2013;73(5):407-426.PubMedGoogle ScholarCrossref
Schnoll  RA, Patterson  F, Wileyto  EP,  et al.  Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial.  Ann Intern Med. 2010;152(3):144-151.PubMedGoogle ScholarCrossref
Fucito  LM, Bars  MP, Forray  A,  et al.  Addressing the evidence for FDA nicotine replacement therapy label changes: a policy statement of the Association for the Treatment of Tobacco Use and Dependence and the Society for Research on Nicotine and Tobacco.  Nicotine Tob Res. 2014;16(7):909-914. PubMedGoogle ScholarCrossref
Joseph  AM, Fu  SS, Lindgren  B,  et al.  Chronic disease management for tobacco dependence: a randomized, controlled trial.  Arch Intern Med. 2011;171(21):1894-1900.PubMedGoogle ScholarCrossref
Hall  SM, Humfleet  GL, Muñoz  RF, Reus  VI, Robbins  JA, Prochaska  JJ.  Extended treatment of older cigarette smokers.  Addiction. 2009;104(6):1043-1052.PubMedGoogle ScholarCrossref
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders. ed 4. Washington, DC: American Psychiatric Association; 1994.
Sheehan  DV, Lecrubier  Y, Sheehan  KH,  et al.  The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10 J Clin Psychiatry. 1998;59(suppl 20):22-33.PubMedGoogle Scholar
Heatherton  TF, Kozlowski  LT, Frecker  RC, Fagerström  KO.  The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire.  Br J Addict. 1991;86(9):1119-1127.PubMedGoogle ScholarCrossref
Schnoll  RA, Patterson  F, Wileyto  EP, Tyndale  RF, Benowitz  N, Lerman  C.  Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: a validation study.  Pharmacol Biochem Behav. 2009;92(1):6-11.PubMedGoogle ScholarCrossref
Brown  R, Burgess  E, Sales  S, Whiteley  J.  Reliability and validity of a smoking timeline follow-back interview.  Psychol Addict Behav. 1998;12(2):101-112.Google ScholarCrossref
Goelz  PM, Audrain-McGovern  JE, Hitsman  B,  et al.  The association between changes in alternative reinforcers and short-term smoking cessation.  Drug Alcohol Depend. 2014;138:67-74.PubMedGoogle ScholarCrossref
SRNT Subcommittee on Biochemical Verification.  Biochemical verification of tobacco use and cessation.  Nicotine Tob Res. 2002;4(2):149-159. PubMedGoogle ScholarCrossref
Hughes  JR, Keely  JP, Niaura  RS, Ossip-Klein  DJ, Richmond  RL, Swan  GE.  Measures of abstinence in clinical trials: issues and recommendations.  Nicotine Tob Res. 2003;5(1):13-25. PubMedGoogle ScholarCrossref
Mooney  M, White  T, Hatsukami  D.  The blind spot in the nicotine replacement therapy literature: assessment of the double-blind in clinical trials.  Addict Behav. 2004;29(4):673-684.PubMedGoogle ScholarCrossref
Schnoll  RA, Epstein  L, Audrain  J,  et al.  Can the blind see? participant guess about treatment arm assignment may influence outcome in a clinical trial of bupropion for smoking cessation.  J Subst Abuse Treat. 2008;34(2):234-241.PubMedGoogle ScholarCrossref
Shiffman  S, Sweeney  CT, Ferguson  SG, Sembower  MA, Gitchell  JG.  Relationship between adherence to daily nicotine patch use and treatment efficacy: secondary analysis of a 10-week randomized, double-blind, placebo-controlled clinical trial simulating over-the-counter use in adult smokers.  Clin Ther. 2008;30(10):1852-1858.PubMedGoogle ScholarCrossref
Original Investigation
April 2015

Long-term Nicotine Replacement Therapy: A Randomized Clinical Trial

Author Affiliations
  • 1Department of Psychiatry, University of Pennsylvania, Philadelphia
  • 2National Comprehensive Cancer Network, Ft Washington, Pennsylvania
  • 3Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
  • 4Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Presbyterian Medical Center, Philadelphia
  • 5Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia
JAMA Intern Med. 2015;175(4):504-511. doi:10.1001/jamainternmed.2014.8313

Importance  The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the standard 8 weeks. This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit.

Objective  To compare 8 (standard), 24 (extended), and 52 (maintenance) weeks of nicotine patch treatment for promoting tobacco abstinence.

Design, Setting, and Participants  We recruited 525 treatment-seeking smokers for a randomized clinical trial conducted from June 22, 2009, through April 15, 2014, through 2 universities.

Interventions  Smokers received 12 smoking cessation behavioral counseling sessions and were randomized to 8, 24, or 52 weeks of nicotine patch treatment.

Main Outcomes and Measures  The primary outcome was 7-day point prevalence abstinence, confirmed with breath levels of carbon monoxide at 6 and 12 months (intention to treat).

Results  At 24 weeks, 21.7% of participants in the standard treatment arm were abstinent, compared with 27.2% of participants in the extended and maintenance treatment arms (χ21 = 1.98; P = .17). In a multivariate model controlled for covariates, participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the standard treatment arm (odds ratio [OR], 1.70 [95% CI, 1.03-2.81]; P = .04), had a longer duration of abstinence until relapse (β = 21.30 [95% CI, 10.30-32.25]; P < .001), reported smoking fewer cigarettes per day if not abstinent (mean [SD], 5.8 [5.3] vs 6.4 [5.1] cigarettes per day; β = 0.43 [95% CI, 0.06-0.82]; P = .02), and reported more abstinent days (mean [SD], 80.5 [38.1] vs 68.2 [43.7] days; OR, 1.55 [95% CI, 1.06-2.26]; P = .02). At 52 weeks, participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the standard and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003).

Conclusions and Relevance  The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers.

Trial Registration  clinicaltrials.gov Identifier: NCT01047527