The American Journal of Medicine
Volume 121, Issue 4, Supplement , Pages S20-S31 , April 2008

Update on Pharmacologic Options for Smoking Cessation Treatment

  • Mitchell Nides, PhD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Mitchell Nides, PhD, Los Angeles Clinical Trial Picture Quitting, the Entertainment Industry’s Quit Smoking Program, 4116 West Magnolia Boulevard, Suite 100, Burbank, California 91505.

References 

  1. Guide to Quitting Smoking. Atlanta, GA: American Cancer Society; 2006;
  2. Centers for Disease Control and Prevention. Cigarette smoking among adults—United States, 2000. MMWR Morb Mortal Wkly Rep. 2002;51:642–645
  3. Centers for Disease Control and Prevention. Cigarette smoking among adults—United States, 2004. MMWR Morb Mortal Wkly Rep. 2005;54:1121–1124
  4. Hughes JR, Keely J, Naud S. Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction. 2004;99:29–38
  5. Shiffman S, Gnys M, Richards TJ, Paty JA, Hickcox M, Kassel JD. Temptations to smoke after quitting: a comparison of lapsers and maintainers. Health Psychol. 1996;455–461
  6. Shiffman S, Waters AJ. Negative affect and smoking lapses: a prospective analysis. J Consult Clin Psychol. 2004;72:192–201
  7. Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry. 1986;43:289–294
  8. Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition. Washington, DC: American Psychiatric Association; 2000;
  9. Cummings KM, Giovino G, Jaen CR, Emrich LJ. Reports of smoking withdrawal symptoms over a 21 day period of abstinence. Addict Behav. 1985;10:373–381
  10. Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and Dependence: Clinical Practice Guideline. Rockville, MD: US Dept of Health and Human Services, Public Health Service (in press).
  11. Henningfield JE, Fant RV, Buchhalter AR, Stitzer ML. Pharmacotherapy for nicotine dependence. CA Cancer J Clin. 2005;55:281–299
  12. Nides M. Optimizing nicotine replacement therapy: patient matching and patient choice. Presented at the National Cancer Institute’s Tobacco Control Investigators Meeting; June 2, 2004; San Diego, California.
  13. Schneider NG, Terrace S, Koury MA, et al. Comparison of three nicotine treatments: initial reactions and preferences with guided use. Psychopharmacology (Berl). 2005;182:545–550
  14. Schneider NG, Olmstead RE, Nides M, et al. Comparative testing of 5 nicotine systems: initial use and preferences. Am J Health Behav. 2004;28:72–86
  15. Gross J, Stitzer ML. Nicotine replacement: ten-week effects on tobacco withdrawal symptoms. Psychopharmacology (Berl). 1989;98:334–341
  16. Foulds J, Burke M, Steinberg M, et al. Advances in pharmacotherapy for tobacco dependence. Expert Opin Emerg Drugs. 2004;9:39–53
  17. Benowitz NL. Nicotine replacement therapy: what has been accomplished—can we do better?. Drugs. 1993;45:157–170
  18. Benowitz NL, Porchet H, Sheiner L, Jacob P. Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther. 1988;44:23–28
  19. Johansson CJ, Olsson P, Bende M, et al. Absolute bioavailability of nicotine applied to different nasal regions. Eur J Clin Pharmacol. 1991;41:585–588
  20. Henningfield JE. Nicotine medications for smoking cessation. N Engl J Med. 1995;333:1196–1203
  21. Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2004;3:CD000146
  22. 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;159:2033–2038
  23. Cepeda-Benito A, Reynoso JT, Erath S. Meta-analysis of the efficacy of nicotine replacement therapy for smoking cessation: differences between men and women. J Consult Clin Psychol. 2004;72:712–722
  24. 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
  25. Hubbard R, Lewis S, Smith C, et al. Use of nicotine replacement therapy and the risk of acute myocardial infarction, stroke, and death. Tob Control. 2005;14:416–421
  26. 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
  27. Zyban (bupropion hydrochloride) sustained-release tablets [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2005;
  28. Fryer JD, Lukas RJ. Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine. J Pharmacol Exp Ther. 1999;288:88–92
  29. Cryan JF, Bruijnzeel AW, Skjei KL, Markou A. Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology (Berl). 2003;168:347–358
  30. Lerman C, Roth D, Kaufmann V, et al. Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Drug Alcohol Depend. 2002;67:219–223
  31. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2004;4:CD000031
  32. Jorenby D. Clinical efficacy of bupropion in the management of smoking cessation. Drugs. 2002;62(suppl 2):25–35
  33. Gonzales D, Bjornson W, Durcan MJ, et al. Effects of gender on relapse prevention in smokers treated with bupropion SR. Am J Prev Med. 2002;22:234–239
  34. Nides M, Rand C, Dolce J, et al. Weight gain as a function of smoking cessation and 2-mg nicotine gum use among middle-aged smokers with mild lung impairment in the first 2 years of the Lung Health Study. Health Psychol. 1994;13:354–361
  35. Doherty K, Militello FS, Kinnunen T, Garvey AJ. Nicotine gum dose and weight gain after smoking cessation. J Consult Clin Psychol. 1996;64:799–807
  36. 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
  37. Dunner DL, Zisook S, Billow AA, et al. A prospective safety surveillance study for bupropion sustained-release in the treatment of depression. J Clin Psychiatry. 1998;59:366–373
  38. Boshier A, Wilton LV, Shakir SA. Evaluation of the safety of bupropion (Zyban 3) for smoking cessation from experience gained in general practice use in England in 2000. Eur J Clin Pharmacol. 2003;59:767–773
  39. Tonstad S, Farsang C, Klaene G, et al. Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study. Eur Heart J. 2003;24:946–955
  40. Chantix (varenicline) [prescribing information]. New York: Pfizer Inc; 2006;
  41. Coe JW, Brooks PR, Vetelino MG, et al. Varenicline: an α4β2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005;48:3474–3477
  42. Rollema H, Chambers LK, Coe JW, et al. Pharmacological profile of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology. 2007;52:985–994
  43. Picciotto MR, Zoli M, Rimondini R, et al. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature. 1998;391:173–177
  44. Tapper AR, McKinney SL, Nashmi R, et al. Nicotine activation of α4* receptors: sufficient for reward, tolerance, and sensitization. Science. 2004;306:1029–1032
  45. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296:47–55
  46. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296:56–63
  47. Tsai ST, Cho HJ, Cheng HS, et al. A randomized, placebo-controlled trial of varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clin Ther. 2007;29:1027–1039
  48. Nakamura M, Oshima A, Fuijmoto Y, et al. Efficacy and tolerability of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther. 2007;29:1040–1056
  49. Tonstad S, Tonnesen P, Hajek P, et al. Effect of maintenance therapy with varenicline for smoking cessation. JAMA. 2006;296:64–71
  50. Hays JT, Ebbert JO, Sood A. Efficacy and safety of varenicline for smoking cessation. Am J Med. 2008;121(4A):S32–S42
  51. Ohlsen RI, Pilowsky LS. The place of partial agonism in psychiatry: recent developments. J Psychopharmacol. 2005;19:408–413
  52. Hughes JR, Stead LF, Lancaster T. Nortriptyline for smoking cessation: a review. Nicotine Tob Res. 2005;7:491–499
  53. Pamelor (nortriptyline HCl) [prescribing information]. St. Louis, MO: Mallinckrodt, Inc; 2006;
  54. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 2nd ed. Arlington, VA: American Psychiatric Association; 2000;
  55. Hall SM, Reus VI, Munoz RF, et al. Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking. Arch Gen Psychiatry. 1998;55:683–690
  56. Catapres (clonidine hydrochloride USP) [prescribing information]. Ridgefield, CTBoehringer Ingelheim. 1998;
  57. Catapres transdermal therapeutic system [prescribing information]. Ridgefield, CTBoehringer Ingelheim. 2006;
  58. Gowing L, Farrell M, Ali R, White J. α2 Adrenergic agonists for the management of opioid withdrawal. Cochrane Database Syst Rev. 2003;2:CD002024
  59. Gourlay SG, Benowitz NL. Is clonidine an effective smoking cessation therapy?. Drugs. 1995;50:197–207
  60. Gourlay SG, Stead LF, Benowitz NL. Clonidine for smoking cessation. Cochrane Database Syst Rev. 2004;3:CD000058
  61. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;340:685–691
  62. Steinberg MB, Foulds J, Richardson DL, et al. Pharmacotherapy and smoking cessation at a tobacco dependence clinic. Prev Med. 2006;42:114–119
  63. Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet. 2005;365:1389–1397
  64. Cohen C, Kodas E, Griebel G. CB1 receptor antagonists for the treatment of nicotine addiction. Pharmacol Biochem Behav. 2005;81:387–395
  65. Sanofi-aventis received from the FDA an approvable letter for rimonabant for weight management and a non approvable letter for smoking cessation. [press release]. Paris: sanofi-aventis; February 17, 2006 http://en.sanofi-aventis.com/press/ppc_12724.asp#3Accessed October 19, 2007
  66. Klesges RC, Winders SE, Meyers AW, et al. How much weight gain occurs following smoking cessation? (A comparison of weight gain using both continuous and point prevalence abstinence). J Consult Clin Psychol. 1997;65:286–291
  67. Fagerström K, Balfour DJ. Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Expert Opin Investig Drugs. 2006;15:107–116
  68. Rimonabant regulatory update in the United States. Paris: sanofi-aventis; June 29, 2007 http://en.sanofi-aventis.com/press/ppc_18223.aspAccessed October 19, 2007
  69. CHMP approves labelling update of Acomplia in Europe and confirms the positive benefit-risk profile of the product except in patients suffering from ongoing major depression. [press release]. Paris: sanofi-aventis; July 19, 2007 http://en.sanofi-aventis.com/press/ppc_18633.asp#3Accessed October 22, 2007
  70. Cohen C, Perrault G, Voltz C, et al. SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats. Behav Pharmacol. 2002;13:451–463
  71. Cohen C, Perrault G, Griebel G, Soubrie P. Nicotine-associated cues maintain nicotine-seeking behavior in rats several weeks after nicotine withdrawal: reversal by the cannabinoid (CB1) receptor antagonist, rimonabant (SR141716). Neuropsychopharmacology. 2005;30:145–155
  72. Reynolds J, Campbell RK. Emerging treatment for diabetes, obesity, and smoking. US Pharmacist. 2005;11:75–79Available at: http://www.uspharmacist.com/index.asp?show=article&page=8_1627.htm. Accessed July 18, 2007
  73. Acomplia (rimonabant). [Summary of Product Characteristics document]. Paris: sanofi-aventis; August 31, 2007 http://www.sanofi-aventis.co.uk/products/Acomplia_SPC.pdfAccessed January 20, 2008
  74. Hatsukami DK, Rennard S, Jorenby D, et al. Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Clin Pharmacol Ther. 2005;78:456–467
  75. Pentel PR, Malin DH, Ennifar S, et al. A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav. 2000;65:191–198
  76. de Villiers SH, Lindblom N, Kalayanov G, et al. Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat nucleus accumbens shell. Respiration. 2002;69:247–253
  77. Lesage MG, Keyler DE, Hieda Y, et al. Effects of a nicotine conjugate vaccine on the acquisition and maintenance of nicotine self-administration in rats. Psychopharmacology (Berl). 2006;184:409–416
  78. Lindblom N, de Villiers SH, Kalayanov G, et al. Active immunization against nicotine prevents reinstatement of nicotine-seeking behavior in rats. Respiration. 2002;69:254–260
  79. Vaccine to treat nicotine addiction promotes 12 months continuous abstinence in subjects who achieve high antibody levels [press release]. Zurichy: Cytos Biotechnology; 2005;
  80. Anti-smoking vaccine TA-NIC preliminary 12 month clinical trial results [press release]. Berkshire, United Kingdom: Xenova Group; 2005;
  81. Nabi Biopharmaceuticals initiates phase IIB “proof-of-concept” study for NicVAX [press release]. Boca Raton, FL: Nabi Biopharmaceuticals; 2006;
  82. Niaura R. Nonpharmacologic therapy for smoking cessation: characteristics and efficacy of current approaches. Am J Med. 2008;121(4A):S11–S19

 Statement of conflict of interest: Please see Author Disclosures section at the end of this document.

PII: S0002-9343(08)00105-8

doi: 10.1016/j.amjmed.2008.01.016

The American Journal of Medicine
Volume 121, Issue 4, Supplement , Pages S20-S31 , April 2008

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