Varenicline: A review of the literature and place in therapy
Evidence regarding the health consequences of smoking is undeniable, yet 21% of the American population continues to smoke. In addition to behavioral modifications, first-line treatment options include nicotine replacement therapies and bupropion SR. Varenicline, which was recently approved by the Food and Drug Administration (FDA), offers a novel mechanism of action for smoking cessation. This article reviews current first-line smoking cessation aids and evaluates the clinical trials pertaining to the efficacy and safety of varenicline. Additionally, the authors attempt to establish the role of varenicline in smoking cessation therapy and determine whether varenicline should be used prior to other first-line smoking cessation aids, particularly considering the lower costs of generic alternatives. At present, clinical studies have not established the efficacy of varenicline after repeated courses, following bupropion failures, or in various unstudied populations. Relatively poor study outcomes emphasize the need to provide patients with behavioral counseling throughout each quit attempt and for 1 year past the quit date.
2. American Cancer Society. Cigarette Smoking. (revised 11-14-2003) Available on line at: http://www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp. Accessed November 29, 2006.
3. Centers for Disease Control and Prevention. Annual smoking-attributable mortality, years of potential life lost, and productivity lost – United States, 1997-2001. MMWR 2005;54(25):625-8.
4. Centers for Disease Control and Prevention (CDC). Tobacco use among adults – United States 2005. 2006;55(42):1146-53.
5. Centers for Disease Control and Prevention. Annual Smoking-Attributable Mortality, Years of Potential Life Lost, and Economic Costs --- United States, 1995—1999. MMWR 2002;51(14):300-3.
6. Benowitz NL. Nicotine addiction. Primary Care 1999;26:611-31.
7. Prochaska JO, DiClemente CC, Norcross JC. In search of how people change: Applications to addictive behaviors. Am Psychol 1992;47(9):1102–4.
8. Leave the pack behind, World no-tobacco day. World Health Organization. May 1999.
9. Benowitz NL.. Cigarette smoking and nicotine addiction. Med Clin North Am 1992;76(2):415-37.
10. Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract 2006;60(5):571–6.
11. Balfour DJ, Fägerstrom KO. Pharmacology of nicotine and its therapeutic use in smoking cessation and neurodegenerative disorders. Pharmacol Ther 1996;72:51-81.
12. Schelling TC. Addictive drugs: the cigarette experience. Science 1992;255:430-3.
13. Smoke-free Workplaces. The World Bank. October 2003. Accessed: November 28, 2006. at: http://web.worldbank.org/WBSITE/EXTERNAL/TOPICS/EXTHEALTHNUTRITIONANDPOPULATION/EXTPHAAG/0,,contentMDK:20796948~menuPK:1314827~pagePK:64229817~piPK:64229743~theSitePK:672263,00.html
14. US Department of Health and Human Services. Healthy people 2010: understanding and improving health. 2nd ed. Washington, DC: US Department of Health and Human Services; 2000. Available at http://www.healthypeople.gov.
15. Dani JA, de Biasi M. Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav 2001;70:439-446.
16. Mansvelder HD, McGehee DS. Cellular and synaptic mechanisms of nicotine addiction. J Neurobiol 2002;53:606-17.
17. Fiore MC, Bailey, WC, Cohen SJ, et al. Treating Tobacco Use and Dependence. Clinical Practice Guidelines. Rockville, MD: US Department of Health and Human Services. Public Health Service. October 2000.
18. Foulds J, Gandhi KK, Steinberg MB et al. Factors associated with quitting smoking at a tobacco dependence treatment clinic. Am J Health Behav 2006; 30: 400-12.
19. Hall SM, Humfleet GL, Reus VI et al. Extended nortriptyline and psychological treatment for cigarette smoking. Am J Psychiatry 2004; 161: 2100–7.
20. Steinberg MB, Foulds J, Richardson DL et al. Pharmacotherapy and smoking cessation at a tobacco dependence clinic. Prev Med 2006; 42: 114–9.
21. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 1999;159:2033-8.
22. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database of Syst Rev 2001;(3):CD000146.
23. New weapon to curb smoking. No more excuses to delay treatment. Arch Intern Med 2006;166:1547-1550.
24. Gourlay SG, McNeil JJ. Antismoking products. Med J Aust 1990;153:699-707.
25. West R, Hajek P, Foulds J, Nilsson F, May S, Meadows A. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray, and inhaler. Psychopharmacology (Berl) 2000;149:198-202.
26. 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;31:171-6.
27. Puska P, Korhonen HJ, Vartiainen E, Urjanheimo EL, Gustavsson G, Westin A. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: a clinical trial in North Karelia. Tobacco Control 1995;4:231-5.
28. Blondal T, Gudmundsson LJ, Olafsdottir I, Gustavsson G, Westin A. Nicotine nasal spray with nicotine patch for smoking cessation: randomized trial with six year follow up. BMJ 1999;318:285-9.
29. Bohadana A, Nilsson F, Rasmussen T, Martinet Y. 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.
30. Tonnesen P, Mikkelsen KL. Smoking cessation with four nicotine replacement regimens in a lung clinic. Eur Respir J 2000;16(4):717-22.
31. Croghan GA, Sloan JA, Croghan IT, Novotny P, Hurt RD, DeKrey WL 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 & Tobacco Research 2003;5(2) :181-7.
32. Hand S, Edwards S, Campbell IA, Cannings R. Controlled trial of three weeks nicotine replacement treatment in hospital patients also given advice and support. Thorax 2002;57(8) :715-8.
33. Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-91.
34. Zyban (package insert). Research Triangle Park, NC: GlaxoSmithKline, DSM Pharmaceuticals, Inc., 2006.
35. McClure JB, Swan GE. Tailoring nicotine replacement therapy; Rationale and potential approaches. CNS Drugs 2006;20(4):281-91.
36. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, et al. Varenicline: An alpha4beta2 Nicotinic Receptor Partial Agonist for Smoking Cessation. J Med Chem 2005;48:3474-77.
37. Chantix (package insert). New York, NY; Pfizer Labs, 2006.
38. Gonzales D, Rennard SI, Nides M, Onchen C, Azoulay S, Billing CB, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation. JAMA 2006;296:47-55.
39. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation. JAMA 2006;296:56-63.
40. Stewart RD. The effect of carbon monoxide on humans. Annu Rev of Pharmacol 1975;15:409-23.
41. Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR. Effect of maintenance therapy with varenicline on smoking cessation. JAMA 2006;296:64-71.
42. McNeill A, Foulds J, Bates C. Regulation of nicotine replacement therapies (NRT): a critique of current practice. Addiction 2004;(4):CD000031.
43. Gonzales DH, Nides MA, Ferry LH, Kustra RP, Jamerson BD, Segall N, Buaron K, Metz A. Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: A randomized placebo-controlled study. Clin Pharmacol Ther 2001;69:438-44.