Can the use of varenicline improve the efficacy of pharmacotherapy for nicotine addiction?

Rafał Mazur 1 , Sebastian Masternak 1 , Michał Pająk 1 , Nikodem Skoczeń 2 , Ewelina Soroka 2  and Marcin Olajossy 2
  • 1 Student Scientific Association by the II Department of Psychiatry and Psychiatric Rehabilitation, Medical University of Lublin
  • 2 II Department of Psychiatry and Psychiatric Rehabilitation, Medical University of Lublin

Abstract

Introduction: Smoking is a huge medical and social problem in Poland, with as many as about 24% of Poles being addicted to nicotine. Approximately 6 million people worldwide die every year from conditions that are closely related to tobacco addiction, such as cancer and cardiovascular, metabolic or lung diseases. The difficulty in combatting nicotine dependence is largely due to the complex mechanism of this addiction. The motivation of a patient to quit smoking is of great importance in the difficult withdrawal process. Strengthening this motivation is one of the most important tasks of physicians and addiction therapists.

Overview of literature: Nicotine replacement therapy (NRT) has been the most widely known way to break away from smoking addiction for many years now. It involves delivering nicotine to the body in ways that are less harmful than through tobacco smoke. As a consequence, the cravings for nicotine are reduced, making it easier for the patient to break with the addiction. Clinical trials have shown that the use of NRT is associated with a 50-70% increased chance of maintaining abstinence from smoking compared to placebo. There are many NRT products, including nicotine chewing gum, nicotine patches, lozenges, dissolvable nicotine sticks, or inhalers. Bupropion is a selective dopamine–noradrenaline reuptake inhibitor. This drug is one of the most commonly used in the pharmacotherapy of depression in the United States. At the same time, it has been found to have a positive effect on people trying to break up with the habit of smoking cigarettes. The mechanism of action remains unknown in this case, but studies clearly indicate the efficacy of bupropion, which is comparable to the efficacy of NRT. Varenicline is a partial agonist selective for α4β2 nicotinic acetylcholine receptors. It has a higher affinity for these receptors than nicotine. By stimulating them, it causes an increase in dopamine secretion (but to a lesser extent than cigarette smoking), helping in this way ease withdrawal symptoms.

Conclusions: Varenicline has higher efficacy than bupropion and NRTs. Simultaneous use of two NRT forms increases the effectiveness of this method to a level comparable to varenicline. Contrary to previous reports, it seems that varenicline does not increase self-aggressive behaviour and the risk of suicide. The effectiveness of antinicotinic drugs depends on the sex of the patient. For both sexes, the most effective drug is varenicline. It is slightly more effective in women than in men. By contrast, NRT and bupropion show greater therapeutic potential in men.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. TNS Polska Ogólnopolskie badanie ankietowe na temat postaw wobec palenia tytoniu, Sierpień 2015.

  • 2. World Health Organization. WHO REPORT ON THE GLOBAL TOBACCO EPIDEMIC: Raising taxes on tobacco, 2015.

  • 3. Henningfield JE, Keenan RM. Nicotine delivery kinetics and abuse liability. J. Consult. Clin. Psychol. 1993; 61(5): 743-750.

  • 4. Hooper MW, Antoni MH, Okuyemi K, Dietz NA, Resnicow K. Randomized Controlled Trial of Group-Based Culturally Specific Cognitive Behavioral Therapy among African American Smokers. Nicotine Tob Res. 2017; 19(3): 333-341.

  • 5. Morell F. MOR A-Therapie – patienteneigene und Farblichtschwingungen. Heidelberg, Haug. German, 1987.

  • 6. Pihtili A, Galle M, Cuhadaroglu C, Kilicaslan Z, Issever H, Erkan F, Cagatay T, Gulbaran Z. Evidence for the Efficacy of a Bioresonance Method in Smoking Cessation: A Pilot Study. Forsch Komplementmed. 2014; 21:239-245.

  • 7. Kostowski W. Współczesna farmakoterapia uzależnienia od nikotyny. Alkoholizm i Narkomania. 2001; 14(1): 129-136.

  • 8. Stead LF, Perera R, Bullen C, Mant D, Hartmann-Boyce J, Cahill K. et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012; DOI: 10.1002/14651858.CD000146.pub4

  • 9. 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: 2033-2038.

  • 10. Beard E, Shahab L, Cummings DM, Michie S, West R. New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What Has Been Investigated, and What Is in the Pipeline? 2016; 30(10): 951-983.

  • 11. Schnoll RA, Goelz PM, Veluz-Wilkins A, Blazekovic S, Powers L, Leone FT. et al. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Intern Med. 2015; 175(4): 504-511.

  • 12. Prochaska JJ. Nicotine Replacement Therapy as a Maintenance Treatment. JAMA. 2015; 314(7): 718–719.

  • 13. A clinical practice guideline for treating tobacco use and dependence: A US Public Health Service report. JAMA. 2000; 283(24): 3244-3254.

  • 14. Bowker KA. Lewis S, Coleman T, Vaz LR, Cooper S. Comparison of cotinine levels in pregnant women while smoking and when using nicotine replacement therapy. Nicotine Tob Res. 2014; 16(6): 895-898.

  • 15. Forinash AB, Pitlick JM, Clark K, Alstat V. Nicotine replacement therapy effect on pregnancy outcomes. Ann Pharmacother. 2010; 44(11): 1817-1821.

  • 16. Scherphof CS, van den Eijnden RJ, Engels RC, Vollebergh WA. Long-term efficacy of nicotine replacement therapy for smoking cessation in adolescents: a randomized controlled trial. Drug Alcohol Depend. 2014; 140: 217-220.

  • 17. Moore D, Aveyard P, Connock M, Wang D, Fry-Smith A, Barton P. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ. 2009; 338: 867-871.

  • 18. Stapleton J, West R, Hajek P, Wheeler J, Vangeli E, Abdi Z. et al. Randomized trial of nicotine replacement therapy (NRT), bupropion and NRT plus bupropion for smoking cessation: effectiveness in clinical practice. Addiction. 2013; 108(12): 2193–2201.

  • 19. Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014; 1. DOI: 10.1002/14651858.CD000031.pub3

  • 20. Hurt RD, Sachs DP, Glover ED, Offord KP, Johnston JA, Dale LC. et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997; 337: 1195-1202.

  • 21. Richmond R, Zwar N. Review of bupropion for smoking cessation. Drug Alcohol Rev. June 2003;22(2):203-220.

  • 22. De Long N, Hyslop JR, Nicholson CJ, Morrison KM, Gerstein HC, Holloway AC. Postnatal metabolic and reproductive consequences of fetal and neonatal exposure to the smoking cessation drug bupropion. Reprod Sci. 2013; 20(10): 1156-1161.

  • 23. Kautiainen K, Ekroos H, Puhakka M, Liira H, Laine J, Linden K. et al. Retreatment with varenicline is a cost-effective aid for smoking cessation. J Med Econ. 2017; 20(3): 246-252.

  • 24. Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J. et al. Varenicline: an α4β2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005; 48(10): 3474-7.

  • 25. Hajek P, McRobbie HJ, Myers KE, Stapleton J, Dhanji AR. Use of varenicline for 4 weeks before quitting smoking: decrease in ad lib smoking and increase in smoking cessation rates. Arch Intern Med. 2011; 171(8): 770-777.

  • 26. Gonzales D, Hajek P, Pliamm L, Nackaerts K, Tseng LJ, McRae TD. et al. Retreatment With Varenicline for Smoking Cessation in Smokers Who Have Previously Taken Varenicline: A Randomized, Placebo-Controlled Trial. Clin Pharmacol Ther. 2014; 96(3): 390-396.

  • 27. Chantix® [package insert]. New York, NY: Pfizer Labs, 2014.

  • 28. Tabex® [package insert]. Sofia, Bulgaria: Sopharma AD, 2016.

  • 29. Vinnikov D, Brimkulov N, Burjubaeva A. A double-blind, randomized, placebo-controlled trial of cytisine for smoking cessation in medium-dependent workers. The Journal of Smoking Cessation. 2008; 3(01): 57-62.

  • 30. West R, Zatonski W, Cedzynska M, Lewandowska D, Pazik J, Aveyard P. et al. Placebo-Controlled Trial of Cytisine for Smoking Cessation. N Engl J Med. 2011; 365(13): 1193-1200.

  • 31. Zhuang Y, Cummins SE, Sun JY, Zhu SH. Long-term e-cigarette use and smoking cessation: a longitudinal study with US population. Tobacco Control. 2016; 25: 90-95.

  • 32. Beard E, Shahab L, Cummings DM, Michie S, West R. New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What Has Been Investigated, and What Is in the Pipeline? CNS Drugs. 2016; 30(10): 951-83.

  • 33. McRobbie H, Bullen C, Hartmann-Boyce J, Hajek P. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev. 2014; 12. DOI: 10.1002/14651858.CD010216.pub2

  • 34. Hughes JR., Stead LF., Lancaster T. Nortriptyline for smoking cessation: a review. Nicotine Tob Res. 2005; 7(4): 491–499.

  • 35. Cinciripini PM, Tsoh JY, Wetter DW, Lam C, de Moor C, Cinciripini L, et al. Combined effects of venlafaxine, nicotine replacement, and brief counseling on smoking cessation. Exp Clin Psychopharmacol. 2005; 13(4): 282-292.

  • 36. Sarginson JE, Killen JD, Lazzeroni LC, Fortmann SP, Ryan HS, Ameli N, et al. Response to transdermal selegiline smoking cessation therapy and markers in the 15q24 chromosomal region. Nicotine Tob Res. 2015; 17(9): 1126–1133.

  • 37. Gourlay SG, Stead LF, Benowitz NL. Clonidine for smoking cessation. Cochrane Database Syst Rev. 2004; 3. DOI: 10.1002/14651858.CD000058.pub2

  • 38. Leggio L, Zywiak WH, Edwards SM, Tidey JW, Swift RM, Kenna GA. A preliminary double-blind, placebo controlled randomized study of baclofen effects in alcoholic smokers. Psychopharmacology. 2015; 232(1): 233–243.

  • 39. Oncken C, Arias AJ, Feinn R, Litt M, Covault J, Sofuoglu M, et al. Topiramate for smoking cessation: a randomized, placebocontrolled pilot study. Nicotine Tob Res. 2014; 16(3): 288–296.

  • 40. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013. Doi: 10.1002/14651858.CD009329.pub2

  • 41. Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, et al. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014; 311(2): 155-163.

  • 42. Ramon JM, Morchon S, Baena A, Masuet-Aumatell C. Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation. BMC Medicine. 2014; 12: 172.

  • 43. Koegelenberg CF, Noor F, Bateman ED, van Zyl-Smit R.N, Bruning A, O’Brien JA, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA. 2014; 312(2): 155-161.

  • 44. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews. 2013; 5. DOI: 10.1002/14651858.CD009329.pub2

  • 45. Wetter DW, Cofta-Gunn L, Fouladi RT, Cinciripini PM, Sui D, Gritz ER. Late relapse/sustained abstinence among former smokers: a longitudinal study. Prev Med. 2004; 39: 1156-1163.

  • 46. Krall EA, Garvey AJ, Garcia RI. Smoking relapse after 2 years of abstinence: findings from the VA Normative Aging Study. Nicotine Tob Res. 2002; 4 (1): 95-100.

  • 47. Smith P, Weinberger A, Zhang J, Emme E, Mazure C, McKee S. Sex Differences in Smoking Cessation Pharmacotherapy Comparative Efficacy: A Network Meta-analysis. Nicotine and Tobacco Research. 2017; 19(3): 273-281.

  • 48. Hughes JR. Varenicline as a Cause of Suicidal Outcomes, Nicotine & Tobacco Research. 2015; 18(1): 2-9.

  • 49. Tadrous M, Martins D, Yao Z, Mamdani MM, Juurlink DN, Gomes T, et al. Varenicline and Risk of Self-Harm: A Nested Case-Control Study. PLoS One. 2016; 11(9). DOI: 10.1371/journal.pone.0163681

  • 50. Zyban® [package insert]. Greenville, SC: GlaxoSmithKline, 2011.

  • 51. Steensland P, Simms JA, Holgate J, Richards JK, Bartlett SE, Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc. Natl. Acad. 2007; 104(30): 12518-12523.

  • 52. Wouda JA, Riga D, De Vries W, Stegeman M, van Mourik Y, Schetters D, et al. Varenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control, Psychopharmacology. 2011; 216 (2): 267-277

  • 53. Kaminski BJ, Weerts EM. The effects of varenicline on alcohol seeking and self-administration in baboons Alcohol. Clin. Exp. Res. 2014; 38 (2): 376-383.

  • 54. Jorenby DE1, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. 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; 296: 56.

  • 55. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006; 296: 47.

OPEN ACCESS

Journal + Issues

Search