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Combination Pharmacotherapy for Stopping Smoking

What Advantages Does it Offer?

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Abstract

Globally, tobacco kills almost 5 million people around the world annually. Seven first-line pharmacotherapies are currently available and recommended by the United States Public Health Service (USPHS) clinical practice guideline for treating tobacco dependence, all of which have been proven to be effective for increasing tobacco abstinence rates when used as monotherapy. However, not all smokers are able to quit with single-drug therapy. Some smokers may benefit from combination therapy that includes the simultaneous use of different nicotine replacement therapies (NRTs) or medications with different mechanisms of action (e.g. NRT and bupropion). Combination therapy with different types of NRT may provide a therapeutic advantage by increasing serum nicotine concentrations, and combination therapy with different drugs may capitalize on synergy obtained from two different mechanisms of action. However, controversy exists regarding this approach. Available data suggests that combination therapy may increase abstinence rates compared with monotherapy. However, the cost effectiveness of this approach has not been clearly demonstrated.

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References

  1. World Health Organization. The facts about smoking and health. 2006 May 30 [online]. Available from URL: http://www.wpro.who.int/media_centre/fact_sheets/fs_20060530.htm [Accessed 2008 Sep 24]

  2. U.S. Department of Health and Human Services. The health consequences of smoking: nicotine addiction. A report of the Surgeon General. Washington, DC: U.S. Government Printing Office, 1988. DHHS publication no. 88-8406

  3. Koob GF. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992 May; 13(5): 177–84

    Article  PubMed  CAS  Google Scholar 

  4. U.S. Department of Health and Human Services. The health benefits of smoking cessation: a report of the Surgeon General, 1990. Washington, DC: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, Office on Smoking and Health, 1990. Publication no. (CDC) 90-8416

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

    Google Scholar 

  6. 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 Jul 5; 296(1): 47–55

    Article  PubMed  CAS  Google Scholar 

  7. 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 Jul 5; 296(1): 56–63

    Article  PubMed  CAS  Google Scholar 

  8. 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 Jan; 103(1): 146–54

    Article  PubMed  Google Scholar 

  9. Aubin HJ, Bobak A, Britton JR, et al. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax 2008 Aug; 63(8): 717–24

    Article  PubMed  Google Scholar 

  10. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2008; (3): CD006103

  11. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 1997 Oct 23; 337(17): 1195–202

    Article  PubMed  CAS  Google Scholar 

  12. Jorenby DE, Leischow SJ, Nides M, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999; 340(9): 685–91

    Article  PubMed  CAS  Google Scholar 

  13. Ebbert JO, Sood A, Hays JT, et al. Treating tobacco dependence: review of the best and latest treatment options. J Thorac Oncol 2007 Mar; 2(3): 249–56

    Article  PubMed  Google Scholar 

  14. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008; (1): CD000146

  15. Sweeney CT, Fant RV, Fagerstrom KO, et al. Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001; 15(6): 453–67

    Article  PubMed  CAS  Google Scholar 

  16. Hajek P, West R, Foulds J, et al. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 1999; 159: 2033–8

    Article  PubMed  CAS  Google Scholar 

  17. Puska P, Korhonen HJ, 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: 231–5

    Article  Google Scholar 

  18. 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(1): 41–7

    Article  PubMed  CAS  Google Scholar 

  19. Fagerstrom KO, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology (Berl) 1993; 111(3): 271–7

    Article  CAS  Google Scholar 

  20. Croghan GA, Sloan JA, Croghan IT, et al. Comparison of nicotine patch alone versus nicotine nasal spray alone versus a combination for treating smokers: a minimal intervention, randomized multicenter trial in a nonspecialized setting. Nicotine Tob Res 2003 Apr; 5(2): 181–7

    Article  PubMed  CAS  Google Scholar 

  21. 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: 285–8

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Article  PubMed  CAS  Google Scholar 

  23. Smith SS, McCarthy DE, Japuntich SJ, et al. Comparative effectiveness of 5 smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med 2009 Dec 14; 169(22): 2148–55

    Article  PubMed  Google Scholar 

  24. Piper ME, Smith SS, Schlam TR, et al. A randomized placebo-controlled clinical trial of 5 smoking cessation pharmacotherapies. Arch Gen Psychiatry 2009 Nov; 66(11): 1253–62

    Article  PubMed  Google Scholar 

  25. Croghan IT, Hurt RD, Dakhil SR, et al. Randomized comparison of a nicotine inhaler and bupropion for smoking cessation and relapse prevention. Mayo Clin Proc 2007 Feb; 82(2): 186–95

    PubMed  CAS  Google Scholar 

  26. George TP, Vessicchio JC, Sacco KA, et al. A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Biol Psychiatry 2008 Jun 1; 63(11): 1092–6

    Article  PubMed  CAS  Google Scholar 

  27. Grant KM, Kelley SS, Smith LM, et al. Bupropion and nicotine patch as smoking cessation aids in alcoholics. Alcohol 2007 Aug; 41(5): 381–91

    Article  PubMed  CAS  Google Scholar 

  28. Hughes JR, Kalman D. Do smokers with alcohol problems have more difficulty quitting? Drug Alcohol Depend 2006 Apr 28; 82(2): 91–102

    Article  PubMed  Google Scholar 

  29. Evins AE, Cather C, Culhane MA, et al. A 12-week double-blind, placebo-controlled study of bupropion sr added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. J Clin Psychopharmacol 2007 Aug; 27(4): 380–6

    Article  PubMed  CAS  Google Scholar 

  30. Steinberg MB, Greenhaus S, Schmelzer AC, et al. Triplecombination pharmacotherapy for medically ill smokers: a randomized trial. Ann Intern Med 2009 Apr 7; 150(7): 447–54

    PubMed  Google Scholar 

  31. Aveyard P, Johnson C, Fillingham S, et al. Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial. BMJ 2008 May 31; 336(7655): 1223–7

    Article  PubMed  Google Scholar 

  32. Prochaska AV, Kick S, Steinbrunn C, et al. A randomized trial of nortriptyline combined with transdermal nicotine for smoking cessation. Arch Intern Med 2004 Nov 8; 164(20): 2229–33

    Article  Google Scholar 

  33. Hughes J, Stead L, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007; 1: CD000031

    PubMed  Google Scholar 

  34. Ebbert JO, Croghan IT, Sood A, et al. Varenicline and bupropion sustained-release combination therapy for smoking cessation. Nicotine Tob Res 2009 Mar; 11(3): 234–9

    Article  PubMed  CAS  Google Scholar 

  35. Varenicline and bupropion for smoking cessation (CHANBAN) [ClinicalTrials.gov identifier NCT00935818]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2010 Mar 1]

  36. Smith JW, Mogg A, Tafi E, et al. Ligands selective for alpha4beta2 but not alpha3beta4 or alpha7 nicotinic receptors generalise to the nicotine discriminative stimulus in the rat. Psychopharmacology (Berl) 2007 Feb; 190(2): 157–70

    Article  CAS  Google Scholar 

  37. Faessel HM, Gibbs MA, Clark DJ, et al. Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy smokers. J Clin Pharmacol 2006 Dec; 46(12): 1439–48

    Article  PubMed  CAS  Google Scholar 

  38. Ebbert JO, Burke MV, Hays JT, et al. Combination treatment with varenicline and nicotine replacement therapy. Nicotine Tob Res 2009 May; 11(5): 572–6

    Article  PubMed  CAS  Google Scholar 

  39. Cornuz J, Gilbert A, Pinget C, et al. Cost-effectiveness of pharmacotherapies for nicotine dependence in primary care settings: a multinational comparison. Tob Control 2006 Jun; 15(3): 152–9

    Article  PubMed  CAS  Google Scholar 

  40. Schnoll RA, Patterson F, Wileyto EP, et al. Effectiveness of extended-duration transdermal nicotine therapy: a randomized trial. Ann Intern Med 2010 Feb 2; 152(3): 144–51

    PubMed  Google Scholar 

  41. Song F, Raftery J, Aveyard P, et al. Cost-effectiveness of pharmacological interventions for smoking cessation: a literature review and a decision analytic analysis. Med Decis Making 2002 Sep–Oct; 22 (5 Suppl.): S26–37

    Article  PubMed  Google Scholar 

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Acknowledgements

This project was supported by the National Cancer Institute Award (CA 138417Z). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. The funding organization had no role in the preparation, review or approval of the manuscript.

JOE has no conflicts of interest to disclose. JTH has received research funding from Pfizer. RDH has served on advisory boards for Pfizer.

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Authors and Affiliations

  1. Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota, 55905, USA

    Jon O. Ebbert (Associate Professor of Medicine), J. Taylor Hays & Richard D. Hurt

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  1. Jon O. Ebbert
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  2. J. Taylor Hays
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  3. Richard D. Hurt
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Correspondence to Jon O. Ebbert.

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Ebbert, J.O., Hays, J.T. & Hurt, R.D. Combination Pharmacotherapy for Stopping Smoking. Drugs 70, 643–650 (2010). https://doi.org/10.2165/11536100-000000000-00000

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