Skip to main content

Advertisement

Log in

Pharmacologic Agents for Tobacco Dependence Treatment: 2011 Update

  • Nonstatin Drugs (W Borden, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Tobacco use remains the most important worldwide cause of preventable death due mainly to cancer, cardiovascular disease, and chronic lung disease. If the current tobacco pandemic continues for another 20 years, the annual global tobacco-attributable mortality will exceed 8 million. In the US and many European countries, public health and tobacco control efforts combined with effective tobacco dependence treatment using combined behavioral treatment and pharmacotherapy have contributed significantly to steadily declining rates of tobacco use. Subsequent declines in cardiovascular disease and lung cancer death rates are directly attributable to these lower rates of tobacco use. Despite smoking bans, health warnings and effective pharmacotherapy, one in five Americans continue to smoke. Continued research in tobacco dependence treatment has resulted in newer and more effective pharmacotherapy. In this review, we provide a current update of pharmacologic agents for tobacco dependence treatment and a discussion of recent controversy regarding adverse effects of some these medications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Shafey O, Eriksen M, Ross H, Mackay J. The Tobacco Atlas. 3rd ed. Atlanta: American Cancer Society; 2009.

    Google Scholar 

  2. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA. 2004;291:1238–45.

    Article  PubMed  Google Scholar 

  3. Kenfield SA, Stampfer MJ, Rosner BA, Colditz GA. Smoking and smoking cessation in relation to mortality in women. JAMA. 2008;299:2037–47.

    Article  PubMed  CAS  Google Scholar 

  4. Doll R, Peto R, Boreham J, Sutherland I. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ. 2004;328:1519–28.

    Article  PubMed  Google Scholar 

  5. Fiore MC, Jaen CR, Baker TB et al. Treating tobacco use and dependence: 2008 update. Clinical Practice Guidelines. In: Rockville, MD: U.S. Department of Health and Human Services. Public Health Service; May 2008.

  6. Stead LF, Perera R, Bullen C et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2008:CD000146.

  7. • Piper ME, Smith SS, Schlam TR et al. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Arch Gen Psychiatry. 2009, 66:1253–62. This clinical trial demonstrated the efficacy of combination pharmacotherapy by randomizing 1504 patients to 1 of 6 treatment conditions: nicotine lozenge, nicotine patch, sustained-release bupropion, nicotine patch plus nicotine lozenge, bupropion plus nicotine lozenge, or placebo. The nicotine patch plus lozenge produced the greatest benefit relative to placebo for smoking cessation.

    Article  PubMed  Google Scholar 

  8. • Smith SS, McCarthy DE, Japuntich SJ et al.: Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med. 2009;169:2148–55. This study demonstrates the effectiveness of combination pharmacotherapy in a primary care clinic setting. A total of 1346 primary care patients were randomly assigned to 1 of 5 treatments: 3 monotherapies (nicotine patch, nicotine lozenge, and bupropion hydrochloride sustained release [SR]) and 2 combination therapies (patch + lozenge and bupropion SR + lozenge). Combination pharmacotherapy significantly increased abstinence compared with monotherapies.

    Article  PubMed  Google Scholar 

  9. Steinberg MB, Greenhaus S, Schmelzer AC, et al. Triple-combination pharmacotherapy for medically ill smokers: a randomized trial. Ann Intern Med. 2009;150:447–54.

    PubMed  Google Scholar 

  10. • Schnoll RA, Patterson F, Wileyto EP et al.: Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial. Ann Intern Med. 2010;152:144–51. In a clinical trial randomizing 568 smokers to extended use nicotine patch (24 weeks) compared with standard 8-week therapy, extended-duration therapy was superior to standard therapy at both 24 weeks and 52 weeks.

    PubMed  Google Scholar 

  11. Hays JT, Hurt RD, Rigotti NA, et al. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. A randomized, controlled trial. Ann Intern Med. 2001;135:423–33.

    PubMed  CAS  Google Scholar 

  12. Tonstad S, Tonnesen P, Hajek P, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006;296:64–71.

    Article  PubMed  CAS  Google Scholar 

  13. Lerman C, Jepson C, Wileyto EP, et al. Genetic variation in nicotine metabolism predicts the efficacy of extended-duration transdermal nicotine therapy. Clin Pharmacol Ther. 2010;87:553–7.

    Article  PubMed  CAS  Google Scholar 

  14. Zapawa LM, Hughes JR, Benowitz NL, et al. Cautions and warnings on the US OTC label for nicotine replacement: what’s a doctor to do? Addict Behav. 2011;36:327–32.

    Article  PubMed  Google Scholar 

  15. Chan SS, Leung DY, Abdullah AS, et al. A randomized controlled trial of a smoking reduction plus nicotine replacement therapy intervention for smokers not willing to quit smoking. Addiction. 2011;106:1155–63.

    Article  PubMed  Google Scholar 

  16. Moore D, Aveyard P, Connock M, et al. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ. 2009;338:b1024–33.

    Article  PubMed  Google Scholar 

  17. Shiffman S, Ferguson SG, Strahs KR. Quitting by gradual smoking reduction using nicotine gum: a randomized controlled trial. Am J Prev Med. 2009;36:96–104. e101.

    Article  PubMed  Google Scholar 

  18. Hughes JR, Solomon LJ, Livingston AE, et al. A randomized, controlled trial of NRT-aided gradual vs. abrupt cessation in smokers actively trying to quit. Drug Alcohol Depend. 2010;111:105–13.

    Article  PubMed  Google Scholar 

  19. Lindson N, Aveyard P, Hughes JR. Reduction versus abrupt cessation in smokers who want to quit. Cochrane Database Syst Rev. 2010:CD008033.

  20. • Mills EJ, Wu P, Lockhart I, et al. Adverse events associated with nicotine replacement therapy (NRT) for smoking cessation. A systematic review and meta-analysis of one hundred and twenty studies involving 177,390 individuals. Tob Induc Dis 2010, 8:8. In one of the largest meta-analyses of NRT adverse effects published to date, NRT adverse effects were found to be mild overall, and there was no increase in serious adverse events such as depression or anxiety.

    Article  PubMed  Google Scholar 

  21. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997;337:1195–202.

    Article  PubMed  CAS  Google Scholar 

  22. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2007:CD000031.

  23. Schnoll RA, Martinez E, Tatum KL, et al. A bupropion smoking cessation clinical trial for cancer patients. Cancer Causes Control. 2010;21:811–20.

    Article  PubMed  Google Scholar 

  24. Evins AE, Culhane MA, Alpert JE, et al. A controlled trial of bupropion added to nicotine patch and behavioral therapy for smoking cessation in adults with unipolar depressive disorders. J Clin Psychopharmacol. 2008;28:660–6.

    Article  PubMed  CAS  Google Scholar 

  25. Catley D, Harris KJ, Okuyemi KS, et al. The influence of depressive symptoms on smoking cessation among African Americans in a randomized trial of bupropion. Nicotine Tob Res. 2005;7:859–70.

    Article  PubMed  CAS  Google Scholar 

  26. Hayford KE, Patten CA, Rummans TA, et al. Efficacy of bupropion for smoking cessation in smokers with a former history of major depression or alcoholism. Br J Psychiatry. 1999;174:173–8.

    Article  PubMed  CAS  Google Scholar 

  27. Strong DR, Kahler CW, Leventhal AM, et al. Impact of bupropion and cognitive-behavioral treatment for depression on positive affect, negative affect, and urges to smoke during cessation treatment. Nicotine Tob Res. 2009;11:1142–53.

    Article  PubMed  CAS  Google Scholar 

  28. Grant BF, Hasin DS, Chou SP, et al. Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry. 2004;61:1107–15.

    Article  PubMed  Google Scholar 

  29. Hays JT, Schroeder DR, Offord KP, et al. Response to nicotine dependence treatment in smokers with current and past alcohol problems. Ann Behav Med. 1999;21:244–50.

    Article  PubMed  CAS  Google Scholar 

  30. Hurt RD, Dale LC, Offord KP, et al. Nicotine patch therapy for smoking cessation in recovering alcoholics. Addiction. 1995;90:1541–6.

    Article  PubMed  CAS  Google Scholar 

  31. Hays JT, Hurt RD, Decker PA, et al. A randomized, controlled trial of bupropion sustained-release for preventing tobacco relapse in recovering alcoholics. Nicotine Tob Res. 2009;11:859–67.

    Article  PubMed  CAS  Google Scholar 

  32. Boshier A, Wilton LV, Shakir SA. Evaluation of the safety of bupropion (Zyban) for smoking cessation from experience gained in general practice use in England in 2000. Eur J Clin Pharmacol. 2003;59:767–73.

    Article  PubMed  CAS  Google Scholar 

  33. Hubbard R, Lewis S, West J, et al. Bupropion and the risk of sudden death: a self-controlled case-series analysis using The Health Improvement Network. Thorax. 2005;60:848–50.

    Article  PubMed  CAS  Google Scholar 

  34. Beyens MN, Guy C, Mounier G, et al. Serious adverse reactions of bupropion for smoking cessation: analysis of the French Pharmacovigilance Database from 2001 to 2004. Drug Saf. 2008;31:1017–26.

    Article  PubMed  CAS  Google Scholar 

  35. Thase ME, Haight BR, Johnson MC, et al. A randomized, double-blind, placebo-controlled study of the effect of sustained-release bupropion on blood pressure in individuals with mild untreated hypertension. J Clin Psychopharmacol. 2008;28:302–7.

    Article  PubMed  CAS  Google Scholar 

  36. Alwan S, Reefhuis J, Botto LD, et al. Maternal use of bupropion and risk for congenital heart defects. Am J Obstet Gynecol. 2010;203(52):e51–6.

    Google Scholar 

  37. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296:47–55.

    Article  PubMed  CAS  Google Scholar 

  38. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296:56–63.

    Article  PubMed  CAS  Google Scholar 

  39. • Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2011:CD006103. This large systematic review observed that varenicline increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Varenicline was also observed to be superior to bupropion. The main adverse effect of varenicline is nausea but mostly at mild to moderate levels and tending to subside over time.

  40. Rigotti NA, Pipe AL, Benowitz NL, et al. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation. 2010;121:221–9.

    Article  PubMed  CAS  Google Scholar 

  41. Tashkin DP, Rennard S, Hays JT, et al. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest. 2011;139:591–9.

    Article  PubMed  Google Scholar 

  42. U.S. Food and Drug Administration. FDA Drug Safety Communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease. Available at http://www.fda.gov/Drugs/DrugSafety/ucm259161.htm. Accessed June 2011.

  43. • Singh S, Loke YK, Spangler JG, Furberg CD. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011, July 5 [Epub ahead of print]. This meta-analysis of serious cardiovascular events associated with varenicline shows a small but statistically significant increase in cardiovascular events with varenicline compared with placebo.

  44. Hays JT. Varenicline for smoking cessation: is it a heartbreaker? CMAJ. 2011, July 5 [Epub ahead of print].

  45. U.S. Food and Drug Administration. The smoking cessation aids varenicline (marketed as chantix) and bupropion (marketed as zyban and generics): suicidal ideation and behavior. FDA Safety Newsletter. 2009;2:1–4.

    Google Scholar 

  46. • Gunnell D, Irvine D, Wise L et al. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ. 2009, 339:b3805. In a retrospective analysis of 10,973 tobacco-dependent patients who used varenicline in a general practice setting, varenicline treatment was associated with similar rates of depression, self-harm, and suicidal thoughts as NRT. This further supports the growing body of medical literature questioning the causal relationship of varenicline to worsening depression and suicidal ideation.

    Article  PubMed  CAS  Google Scholar 

  47. Tonstad S, Davies S, Flammer M, et al. Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Drug Saf. 2010;33:289–301.

    Article  PubMed  CAS  Google Scholar 

  48. Stapleton JA, Watson L, Spirling LI, et al. Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness. Addiction. 2008;103:146–54.

    Article  PubMed  Google Scholar 

Download references

Disclosure

J.T. Hays has received grants (paid to his institution) from Pfizer and Nabi Biopharmaceuticals. D.D. McFadden had Pfizer reimburse his institution (Mayo Clinic) for Pfizer-sponsored tobacco treatment seminars he conducted in Mexico and South America; Pfizer also covered his travel expenses for those seminars. J.O. Ebbert has been a consultant for and had travel expenses reimbursed by GlaxoSmithKline, and has also received a grant (paid to his institution) from Pfizer.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Taylor Hays.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hays, J.T., McFadden, D.D. & Ebbert, J.O. Pharmacologic Agents for Tobacco Dependence Treatment: 2011 Update. Curr Atheroscler Rep 14, 85–92 (2012). https://doi.org/10.1007/s11883-011-0211-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-011-0211-2

Keywords

Navigation