Pharmacotherapy for Treating Tobacco Dependence

What is the Ideal Duration of Therapy?


Various forms of nicotine replacement therapy and bupropion have been found to be efficacious and well tolerated for treating patients dependent on tobacco. However, the currently recommended duration of treatment with pharmacotherapy may be insufficient for some smokers to achieve sustained abstinence from tobacco. Extending the use of pharmacotherapy beyond the recommended timeframe may be an effective strategy for helping tobacco users achieve abstinence and for preventing relapse to tobacco use, especially among those who are highly dependent and those who are concerned about body weight gain following cessation.

Several studies have reported on long-term use of various pharmacotherapies. These studies have demonstrated that such long-term use is not harmful. Moreover, compared with continued smoking, long-term use of pharmacotherapy exposes patients to relatively small amounts of nicotine and none of the cancer-causing chemicals found in cigarettes and other tobacco products. However, more research is needed to further clarify questions regarding the ideal duration of therapy. Two questions have yet to be answered: In what populations of smokers is long-term therapy an effective strategy for achieving abstinence and preventing relapse? Does wider availability of nicotine replacement therapy lead to initiation of nicotine addiction by children and others not using tobacco products? Also, as with all medications, additional documentation of the safety of prolonged use of pharmacotherapy is important.

The aim of this review is to present the current evidence supporting the notion that long-term therapy for treating tobacco dependence may be appropriately considered for some tobacco users.

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

Table I


  1. 1.

    Use of tradenames is for product identification only and does not imply endorsement.


  1. 1.

    Lichenstein E, Glasgow RE, Abrams DB. Social support in smoking cessation: in search of effective interventions. Behav Ther 1986; 17(5): 607–19

    Article  Google Scholar 

  2. 2.

    Murray RP, Voelker HT, Rakos RF, et al. Intervention for relapse to smoking: the Lung Health Study restart programs. Addict Behav 1997; 22(2): 281–6

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Benowitz NL. Nicotine replacement therapy: what has been accomplishedcan we do better? Drugs 1993; 45(2): 157–70

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Fagerstrom KO. Nicotine replacement: present and future. CVD Prev 1999 Jun; 2(2): 145–9

    Google Scholar 

  5. 5.

    Hughes JR, Higgins ST, Bickel WK. Common errors in the pharmacologic treatment of drug dependence and withdrawal. Compr Ther 1994; 20(2): 89–94

    PubMed  CAS  Google Scholar 

  6. 6.

    Henningfield JE. Nicotine medications for smoking cessation. N Engl J Med 1995 Nov; 333(18): 1196–203

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Physicians’ Desk Reference. 56th ed. Montvale (NJ): Medical Economics Company, Inc., 2002

  8. 8.

    Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: clinical practice guideline. Rockville (MD): US Department of Health and Human Services Public Health Service, 2000 Jun

    Google Scholar 

  9. 9.

    Holm KJ, Spencer CM. Bupropion: a review of its use in the management of smoking cessation. Drugs 2000 Apr; 59(4): 1007–24

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Brigham J, Henningfield JE, Stitzer ML. Smoking relapse: a review. Int J Addict 1991; 25 (9A, 10A): 1239–55

    CAS  Google Scholar 

  11. 11.

    Piasecki TM, Fiore MC, Baker TB. Profiles in discouragement: two studies of variability in the time course of smoking withdrawal symptoms. J Abnorm Psychol 1998; 107(2): 238–51

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Piasecki TM, Niaura R, Shadel WG, et al. Smoking withdrawal dynamics in unaided quitters. J Abnorm Psychol 2000; 109(1): 74–86

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    West R, Hajek P, Foulds J, et al. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmocology (Berl) 2000 Jan; 149: 198–202

    Article  CAS  Google Scholar 

  14. 14.

    Hjalmarson A, Franzon M, Westin A, et al. Effect of nicotine nasal spray on smoking cessation: a randomized, placebo-controlled, double-blind study. Arch Intern Med 1994; 154: 2567–72

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Bohadana A, Nilsson F, Rasmussen T, et al. Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 2000; 160: 3128–34

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Hughes JR. Dependence on and abuse of nicotine replacement medications: an update. In: Benowitz NL, editor. Nicotine safety and toxicity. New York: Oxford University Press, 1998: 147–57

    Google Scholar 

  17. 17.

    Hughes JR. Dependence potential and abuse liability of nicotine replacement therapies. Prog Clin Biol Res 1988; 261: 261–77

    PubMed  CAS  Google Scholar 

  18. 18.

    Hughes JR, Hatsukami DK, Skoog KP. Physical dependence on nicotine in gum: a placebo substitution trial. JAMA 1986; 255: 3277–9

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    West JR, Russell MA. Effects of withdrawal from long-term nicotine gum use. Psychol Med 1985; 15: 891–3

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Hughes JR, Gust SW, Keenan RM, et al. Long-term use of nicotine versus placebo gum. Arch Intern Med 1991 Oct; 151: 1993–8

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Hughes JR, Wadland WC, Fenwick JW, et al. Effect of cost on the self-administration and efficacy of nicotine gum: a preliminary study. Prevent Med 1991; 20: 486–96

    Article  CAS  Google Scholar 

  22. 22.

    Sutherland G, Stapleton JA, Russell MA, et al. Randomised controlled trial of nasal nicotine spray in smoking cessation. Lancet 1992 Aug; 340: 324–9

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Murray RP, Daniels K. Long-term nicotine therapy. In: Benowitz NL, editor. Nicotine safety and toxicity. New York: Oxford University Press, 1998: 173–82

    Google Scholar 

  24. 24.

    Nides MA, Gonzales D, Tashkin DP, et al. Predictors of initial smoking cessation and relapse through the first 2 years of the Lung Health Study. J Consult Clin Psychol 1995; 63(1): 60–9

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Murray RP, Gerald LB, Lindgren PG, et al. Characteristics of participants who stop smoking and sustain abstinence for 1 and 5 years in the Lung Health Study. Prevent Med 2000; 30: 392–400

    Article  CAS  Google Scholar 

  26. 26.

    Hajek P, Jackson P, Belcher M. Long-term use of nicotine chewing gum: occurrence, determinants, and effect on weight gain. JAMA 1988 Sep; 260(11): 1593–6

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Fiore MC, Smith SS, Jorenby DE, et al. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA 1994 Jun; 271(24): 1940–7

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Tønnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Eur Resp J 1999; 13: 238–46

    Article  Google Scholar 

  29. 29.

    Stapleton JA, Sutherland G, Russell MA. How much does relapse after one year erode effectiveness of smoking cessation treatments? Long term follow up of randomised trial of nicotine nasal spray. BMJ 1998 Mar; 316(7134): 830–1

    PubMed  Article  CAS  Google Scholar 

  30. 30.

    Hays JT, Hurt RD, Rigotti NA, et al. Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. Ann Intern Med 2001 Sep; 135(6): 423–33

    PubMed  CAS  Google Scholar 

  31. 31.

    Murray RP, Bailey WC, Daniels K, et al. Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study: Lung Health Study Research Group. Chest 1996 Feb; 109: 438–45

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Hurt RD, Offord KP, Lauger GG, et al. Cessation of long-term nicotine gum use: a prospective, randomized trial. Addiction 1995; 90: 407–13

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Hatsukami D, Huber M, Callies A, et al. Physical dependence on nicotine gum: effect of duration of use. Psychopharmacology (Berl) 1993; 111(4): 449–56

    Article  CAS  Google Scholar 

  34. 34.

    Stratton K, Shetty P, Wallace R, et al. Clearing the smoke: assessing the science base for tobacco harm reduction: Institute of Medicine. Washington, DC: National Academy Press, 2001

    Google Scholar 

  35. 35.

    Hurt RD. Clinical implications of long-term nicotine use. In: Ferrence R, Slade J, Room R, et al., editors. Nicotine and public health: the American Public Health Association. Washington, DC: United Book Press, 2000: 389–428

    Google Scholar 

  36. 36.

    Schuh KJ, Schuh LM, Henningfield JE, et al. Nicotine nasal spray and vapor inhaler: abuse liability assessment. Psychopharmacology (Berl) 1997; 130: 352–61

    Article  CAS  Google Scholar 

  37. 37.

    Russell MA. The future of nicotine replacement. Br J Addict 1991; 86: 653–8

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    Warner KE, Slade J, Sweaner DT. The emerging market for long-term nicotine maintenance. JAMA 1997 Oct; 278(13): 1087–92

    PubMed  Article  CAS  Google Scholar 

  39. 39.

    McNeill A, Foulds J, Bates C. Regulation of nicotine replacement therapies (NRT): a critique of current practice. Addiction 2001; 96: 1757–68

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    National Center for Tobacco-Free Kids: petition for Food and Drug Administration regulation of Activa tobacco lozenges [online]. Available from URL: [Accessed 2002 Jul 16]

  41. 41.

    Henningfield JE. Tobacco dependence treatment: scientific challenges, public health opportunities. Tob Control 2000; 9Suppl. I: i3–i10

    PubMed  Article  Google Scholar 

Download references


This research was supported in part by the National Cancer Institute P50-CA84724 centre grant and minority supplements.

Author information



Corresponding author

Correspondence to Dr Tammy Harris Sims.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sims, T.H., Fiore, M.C. Pharmacotherapy for Treating Tobacco Dependence. Mol Diag Ther 16, 653–662 (2002).

Download citation


  • Nicotine
  • Smoking Cessation
  • Bupropion
  • Withdrawal Symptom
  • Nicotine Replacement Therapy