The pharmacotherapy of smoking cessation

Matthew J Peters and Lucy C Morgan
Med J Aust 2002; 176 (10): 486-490.


  • The great majority of smokers are chronically dependent on tobacco. This dependence arises from the rituals and sensory associations of smoking that are reinforced, within seconds, by a rapid burst of nicotine from the cigarette.

  • All forms of nicotine replacement therapy (NRT) — gum, patches and inhaler — and bupropion are safe and effective for increasing smoking cessation rates in the short and long terms.

  • Other than those who are minimally dependent, all patients willing to quit should be offered one of these therapies unless contraindications exist. The effectiveness of drug treatments is multiplied when associated with effective counselling or behavioural treatments.

  • While NRT is not recommended during pregnancy or in patients with cardiac disease, if the alternative is smoking NRT is almost certainly safe.

  • Combination NRT (more than one therapy) may be indicated in patients who have failed monotherapy in association with withdrawal symptoms.

  • There are some specific contraindications to the use of bupropion. Its subsidised availability should not influence prescribers to ignore these.

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  • Matthew J Peters1
  • Lucy C Morgan2

  • Department of Thoracic Medicine, Concord Repatriation General Hospital, Concord, NSW, Australia.


Competing interests:

M P has conducted clinical trials and received an honorarium from GlaxoSmithKline and support for travel to meetings.

  • 1. 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, June 2000.
  • 2. Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation (Cochrane Review). In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software.
  • 3. Balfour DJ, Wright AE, Benwell ME, Birrell CE. The putative role of extra-synaptic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 2000; 113: 73-83.
  • 4. Stauffer HP, Riedwyl H. Interaction and pH dependence of effects of nicotine and carbon monoxide in cigarette smoke inhalation experiments with rats. Agents Actions 1977; 5-6: 579-588.
  • 5. Zhou FM, Liang Y, Dani JA. Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum. Nat Neurosci 2001; 4: 1224-1229.
  • 6. Tomkins DM, Sellers EM. Addiction and the brain: the role of neurotransmitters in the cause and treatment of drug dependence. CMAJ 2001; 164: 817-821.
  • 7. Pontieri FE, Tanda G, Orzi G, et al. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 1996; 382: 255-257.
  • 8. West R, Hajek P, Foulds J, et al. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl) 2000; 149: 198-202.
  • 9. Schneider NG, Olmstead RE, Franzon MA, Lunell E. The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 2001; 40: 661-684.
  • 10. Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996; 335: 1792-1798.
  • 11. Mahmarian JJ, Moye LA, Nasser GA, et al. Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischaemia. J Am Coll Cardiol 1997; 30: 125-130.
  • 12. National Health and Medical Research Council. A guide to the development, implementation and evaluation of clinical practice guidelines. Canberra: NHMRC, AusInfo, 1999.
  • 13. Wisborg K, Henriksen TB, Jespersen LB, Secher NJ. Nicotine patches for pregnant smokers: a randomised controlled trial. Obstet Gynecol 2000; 96: 967-971.
  • 14. Dempsey DA, Benowitz NL. Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Safety 2001; 24: 277-322.
  • 15. NSW Health. 1999 NSW mothers and babies report. <> (Accesssed 5 Dec, 2001).
  • 16. Aascher JA, Cole JO, Colin JN, et al. Bupropion: a review of its mechanism of anti-depressant activity. J Clin Psychiatry 1995; 56: 395-401.
  • 17. Ferry LH, Robbins AS, Sarlati PD, et al. Enhancement of smoking cessation using the antidepressant, bupropion hydrochloride [abstract]. Circulation 1992; 86: I671.
  • 18. Ferry LH, Burchette RJ. Efficacy of bupropion for smoking cessation in non-depressed smokers. J Addict Dis 1994; 13: 249.
  • 19. Dong J, Blier P. Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment. Psychopharmacology (Berl) 2001; 155: 52-57.
  • 20. Jamerson BD, Nides M, Jorenby DE, et al. Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Clin Ther 2001; 23: 744-752.
  • 21. Benson E. Bupropion induced hypersensitivity reactions. Med J Aust 2001; 174: 650-651.
  • 22. Therapeutic Goods Administration. Update on bupropion (Zyban SR) - 31 August 2001. <> (Accessed 15 Dec, 2001, no longer available).
  • 23. 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: 1119-1127.
  • 24. Centers for Disease Control and Prevention. Smoking cessation during previous year among adults—United States, 1990 and 1991. MMWR Morb Mortal Wkly Rep 1993; 42: 504-507.
  • 25. Hatziandreu EJ, Pierce JP, Lefkopoulou M, et al. Quitting smoking in the United States in 1986. J Natl Cancer Inst 1990; 82: 1402-1406.
  • 26. Effectiveness of interventions to help people stop smoking: findings from the Cochrane Library. BMJ 2000; 321: 355-358.
  • 27. West R, Hajek P, Nilsson F, et al. Individual differences in preferences for and responses to four nicotine replacement products. Psychopharmacology (Berl) 2001; 153: 225-230.
  • 28. Hughes JR, Lesmes GR, Hatsukami DK, et al. Are higher doses of nicotine replacement more effective for smoking cessation? Nicotine Tob Res 1999; 1: 169-174.
  • 29. Killen JD, Fortmann SP, Davis L, et al. Do heavy smokers benefit from higher dose nicotine patch therapy? Exp Clin Psychopharmacol 1999; 7: 226-233.
  • 30. Herrera N, Franco R, Herrera L, et al. Nicotine gum, 2 and 4 mg, for nicotine dependence. A double-blind placebo-controlled trial within a behavior modification support program. Chest 1995; 108: 447-451.
  • 31. Kornitzer M, Kittel F, Dramaix M, Bourdoux P. A double blind study of 2 mg versus 4 mg nicotine-gum in an industrial setting. J Psychosom Res 1987; 31: 171-176.
  • 32. Hurt RD, Sachs DPL, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997; 337: 1195-1202.
  • 33. Gonzales DH, Nides MA, Ferry LH, et al. Bupropion SR as an aid to smoking cessation in smokers previously treated with bupropion; a randomized placebo-controlled study. Clin Pharmacol Ther 2001; 69: 438-444.
  • 34. Kornitzer M, Boutsen M, Dramaix M, et al. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995; 24: 41-47.
  • 35. Puska P, Korhonen H, Vartiainen E, et al. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: a clinical trial in North Karelia. Tob Control 1995; 4: 231-235.
  • 36. Blondal T, Gudmundsson LJ, Olafsdottir I, et al. Nicotine nasal spray with nicotine patch for smoking cessation: Randomized trial with six year follow up. BMJ 1999; 318: 285-288.
  • 37. Hughes JR, Lesmes GR, Hatsukami DK, et al. Are higher doses of nicotine replacement more effective for smoking cessation? Nicotine Tob Res 1999 1: 169-174.
  • 38. Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Eur Respir J 1999; 13: 238-246.
  • 39. 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: 423-433.
  • 40. Hurt RD, Croghan GA, Wolter TD, et al. Does smoking reduction result in reduction of biomarkers associated with harm? A pilot study using a nicotine inhaler. Nicotine Tob Res 2000; 2: 327-336.
  • 41. Hatsukami D, Rennard S, Malcolm R, et al. A multicenter study examining the effects of Zyban (bupropion HCL SR) vs. placebo as an aid to smoking reduction leading to cessation among smokers unwilling and unable to quit smoking [abstract]. Proceedings, 3rd European Conference of the Society for Research on Nicotine and Tobacco. Society for Research on Nicotine and Tobacco, Middleton WI, USA, 2001.
  • 42. Williamson DF, Madans J, Anda RF, et al. Smoking cessation and severity of weight gain in a national cohort. N Engl J Med 1991; 324: 739-745.
  • 43. Hall SM, Tunstall CD, Vila KL, Duffy J. Weight gain prevention and smoking cessation: Cautionary findings. Am J Public Health 1992; 82: 799-803.
  • 44. Emont SC, Cummings KM. Weight gain following smoking cessation: a possible role for nicotine replacement in weight management. Addict Behav 1987; 12: 151-155.
  • 45. 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: 1195-1202.
  • 46. Kawachi I, Troisi RJ, Rotnitzky AG, Coakley EH. Can physical activity minimize weight gain in women after smoking cessation? Am J Public Health 1996; 86: 999-1004.
  • 47. Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry 1986; 143: 993-997.
  • 48. De Leon J, Dadvand M, Canuso C, et al. Schizophrenia and smoking: an epidemiological survey in a state hospital. Am J Psychiatry 1995; 152: 453-455.
  • 49. Lasser K, Wesley Boyd J, Woolhandler S, et al. Smoking and mental illness. A population-based prevalence study. JAMA 2000; 284: 2606-2610.
  • 50. McNeill A. Smoking and mental health: a review of the literature. <> (Accessed 15 Dec 2001).
  • 51. Hertzberg MA, Moore SD, Feldman ME, Beckham JC. A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic post-traumatic stress disorder. J Clin Psychopharmacol 2001; 21: 94-98.
  • 52. Addington J, el-Guebaly N, Campbell W, et al. Smoking cessation treatment for patients with schizophrenia. Am J Psychiatry 1998; 155: 974-976.
  • 53. Evins AE, Mays VK, Rigotti NA, et al. A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. Nicotine Tob Res 2001; 3: 397-403.
  • 54. Killen JD, Fortmann SP, Kraemer HC, et al. Interactive effects of depression symptoms, nicotine dependence, and weight change on late smoking relapse. J Consult Clin Psychol 1996; 64: 1060-1067.
  • 55. 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: 173-178.
  • 56. Glassman AH, Covey LS, Stetner F, Rivelli S. Smoking cessation and the course of major depression: a follow-up study. Lancet 2001; 357: 1929-1932.


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