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VOLUME 9 , ISSUE 2 ( December, 2018 ) > List of Articles


Therapies for Smoking Cessation: A Meta-analysis of Double-blind Randomized Controlled Trials

Dipika Dabas

Keywords : Nicotine spray, Smoking, Therapy,Double blind

Citation Information : Dabas D. Therapies for Smoking Cessation: A Meta-analysis of Double-blind Randomized Controlled Trials. J Health Sci Res 2018; 9 (2):49-56.

DOI: 10.5005/jp-journals-10042-1069

License: CC BY-NC 4.0

Published Online: 00-12-2018

Copyright Statement:  Copyright © 2018; Jaypee Brothers Medical Publishers (P) Ltd.


Background: Several placebo-controlled randomized trials have shown a substantial effect of many products used for smoking cessation. The trials have revealed results by performing either a direct or indirect comparisons. The present metaanalysis is an endeavor to compare the effect of the currently available and widely used seven pharmacological interventions as an aid to smoking cessation. Methods: The databases like MEDLINE, EMBASE and the Cochrane reviewed published trials were investigated and further screened to meet the inclusion criteria. For example, only double-blind randomized controlled trials were included who have validated the results of abstinence at 6 and 12 months biochemically. Results: A total of 69 trials were identified with a total number of 32,908 participants. Out of seven therapies chosen for the analysis, six were found to be more effective than placebo, the odds ratio (OR) for varenicline was 2.41, 95% CI 1.91–3.12, for nicotine spray (OR) 2.37, 95% CI 1.12–5.13, bupropion with (OR) 2.07, 95% CI 1.73–2.55, transdermal nicotine patch (OR) 2.07, 95% CI 1.69–2.62, nicotine tablet (OR) 2.06, 95% CI 169–2.62, and for gum (OR) 1.71, 95% CI 1.35–2.21. Though OR of 2.71 in case of nicotine inhaler favors its effectiveness over placebo, but this result remained inconclusive as the 95% CI, in this case, includes unity (0.95–5.43). On the contrary, when all the seven interventions were analyzed by putting them all together, all of them were found to be effective than a placebo. When varenicline was compared against bupropion (control arm), the former was found to be superior in its effect on smoking cessation than the latter with (OR 2.18, 95 CI% 1.09–4.08). Interpretation: The interventional products used for smoking abstinence for 6 and 12 months, namely varenicline, bupropion, and 5 nicotine replacement therapies like nicotine gum, inhaler, transdermal patch, tablet, and lozenges were all found to be effective than placebo.

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  1. Abelin T, Buehler A, Muller P, et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet 1989;1:7-10.
  2. Abelin T, Ehrsam R, Buhler-Reichert A, et al. Effectiveness of a transdermal nicotine system in smoking cessation studies. Methods Find Exp Clin Pharmacol 1989;11:205-214.
  3. Areechon W, Punnotok J. Smoking cessation through the use of nicotine chewing gum: a double-blind trial in Thailand. Clin Ther 1988;10:183-186.
  4. Ahluwalia JS, Harris KJ, Catley D, et al. Sustained-release bupropion for smoking cessation in African Americans: a randomized controlled trial. JAMA 2002;288:468-474.
  5. Blondal T. Controlled trial of nicotine polacrile x gu m with supportive measures. Arch Intern Med 1989;149:1818-1821.
  6. Campbell IA, Lyons E, Prescott RJ. Stopping smoking. Do nicotine chewing-gu mand postal encouragement add to doctors’ advice. Practitioner 1987;231:114-117.
  7. Cooper TV, Klesges RC, Debon MW, et al. A placebo controlled randomized trial of the effects of phenylpropanolamine and nicotine gum on cessation rates and post cessation weight gain in wo men. Addict Behav 2005;30:61-75.
  8. Daughton D, Sus man J, Sitorius M, et al. Transdermal nicotine therapy and primary care. Importance of counseling, demographic, and participant selection factors on 1-year quit rates. The Nebraska Primary Practice Smoking Cessation Trial Group. Arch Fam Med 1998;7:425-430.
  9. Dalsgareth OJ, Hansen NC, Soes-Petersen U, et al. A multicenter, rando mized, double-blind, placebo- controlled, 6-month trial of bupropion hydrochloride sustained-release tablets as an aid to smoking cessation in hospital employees. Nicotine Tob Res 2004;6:55-61.
  10. Doll R, Peto R, Wheatley K, Gray R, Sutherland I: Mortality in relation to smoking: 40 years’ observations on male British doctors. BMJ 1994;309:901-911.
  11. Daughton DM, Heatley SA, Prendergast JJ, et al. Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. A randomized, placebo-controlled, double-blind study. Arch Intern Med 1991;151:749-752.
  12. Effectiveness of a nicotine patch in helping people stop smoking: results of a randomized trial in general practice. Imperial Cancer Research Fund General Practice Research Group. BMJ 1993;306:1304-1308.
  13. Fee WM, Stewart MJ. A controlled trial of nicotine chewing gum in a smoking withdrawal clinic. Practitioner 1982; 226:148-151.
  14. Fortmann SP, Killen JD, Telch MJ, et al. Minimal contact treatment for smoking cessation. A placebo controlled trial of nicotine polacrilex and self-directed relapse prevention: initial results of the Stanford Stop Smoking Project. JAMA 1988; 260:1575-1580.
  15. Fiore MC, Kenford SL, Jorenby DE, et al. Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments. Chest 1994;105:524-533.
  16. Glavas D, Rumboldt M, Rumboldt Z. Smoking cessation with nicotine replacement therapy among health care workers: randomized double-blind study. Croat Med J 2003;44:219-224.
  17. Garvey AJ, Kinnunen T, Nordstrom BL, et al. Effects of nicotine gum dose by level of nicotine dependence. Nicotine Tob Res 2000;2:53-63.
  18. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR: Varenicline, an alpha4 beta2 nicotinic acetylcholine receptor partial agonist, vs sustained -release Bupropion and placebo for smoking cessation: a randomized controlled trial. Jama 2006;296:47-55.
  19. Gourlay SG, Forbes A, Marriner T, et al. Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers. BMJ 1995;311:363-366.
  20. Glover M. 1997. Smoking cessation services for Maori: advice on purchasing. Wel l ington: New Zealand Central Regional Health Authority. Available online at: Accessed: 11 November 2006.
  21. Hughes J, Stead L, Lancaster T: Antidepressants for smoking cessation. Cochrane Database Syst Rev 2004, CD000031.
  22. Hughes JR, Gust SW, Keenan RM, et al. Nicotine vs placebo gum in general medical practice. JAMA 1989;261:1300-1305.
  23. Hall SM, Humfleet GL, Reus VI, et al. Psychological intervention and anti depressant treatment in smoking cessation. Arch Gen Psychiatry 2002;59:930-936.
  24. Holt S, Timu-Parata C, Ryder-Lewis S, et al. Efficacy of bupropion in the indigenous Maori population in New Zealand. Thorax 2005;60:120-123.
  25. Hall SM, Munoz RF, Reus VI, et al. Mood management and nicotine gum in smoking treatment: a therapeutic contact and placebo-controlled study. J Consult Clin Psychol 1996;64:1003-1009.
  26. Hjalmarson AI. Effect of nicotine chewing gum in smoking cessation. A randomized, placebo-controlled, double-blind study. JAMA 1984;252:2835-2838.
  27. Herrera N, Franco R, Herrera L, et al. Nicotine gum, 2 and 4 mg, for nicotine dependence. A double-blind placebo-controlled trial with in a behavior modification support program. Chest 1995;108:447-451.
  28. Hall SM, Tunstall CD, Ginsberg D, et al. Nicotine gum and behavioral treatment: a placebo controlled trial. J Consult Clin Psychol 1987;55:603-605.
  29. Hays JT, Croghan IT, Schroeder DR, et al. Over-the-counter nicotine patch therapy for smoking cessation: results from randomized, double-blind, placebo-controlled, and open label trials. Am J Public Health 1999;89:1701-1707.
  30. 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.
  31. Hurt RD, Dale LC, Fredrickson PA, et al. Nicotine patch therapy for smoking cessation combined with physician advice and nurse follow-up. One-year outcome and percentage of nicotine replacement. JAMA 1994;271:595-600.
  32. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR. Efficacy of Varenicline, an alpha4 beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustaine-release Bupropion for smoking cessation: a randomized controlled trial. Jama 2006;296:56-63.
  33. 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.
  34. Jones L, Donnelly A, Harneiss C, Warbrick D, Swinn K, Malosi L, et al. A qualitative investigation of the application of behaviour modification to group-quitting for Maori and Pacific smokers. South Pacific Journal of Psychology. 2004;1:43-53.
  35. Jarvik ME, Schneider NG. Degree of addiction and effectiveness of nicotine gum therapy for smoking. Am J Psychiatry 1984;141:790-791.
  36. Jamrozik K, Fowler G, Vessey M, et al. Placebo controlled trial of nicotine chewing gum in general practice. Br Med J (Clin Res Ed) 1984; 289:794-797.
  37. Jarvis MJ, Raw M, Russell MA, et al. Randomized controlled trial of nicotine chewing-gum. Br Med J (Clin Res Ed) 1982;285:537-540.
  38. Killen JD, Fortmann SP, Newman B, et al. Evaluation of a treatment approach combining nicotine gum with selfguided behavioral treatments for smoking relapse prevention. J Consult Clin Psychol 1990;58:85-92.
  39. Kornitzer M, Boutsen M, Dramaix M, et al. Combined use of nicotine patch and gum in smoking cessation: a placebocontrolled clinical trial. Prev Med 1995;24:41-47.
  40. Killen JD, Fortmann SP, Davis L, et al. Nicotine patch and self-help video for cigarette smoking cessation. J Consult Clin Psychol 1997;65:663-672.
  41. Law M, Tang JL: An analysis of the effectiveness of interventions intended to help people stop smoking. Arch Intern Med 1995, 155: 1933-1941.
  42. 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-analyses. BMJ 2009;338:b1024.
  43. Muramoto ML, Leischow SJ, Sherrill D, et al. Randomized, double-blind, placebo controlled trial of 2 dosages of sustained- release bupropion for adolescent smoking cessation. Arch Pediatr Adolesc Med 2007;161:1068-1074.
  44. Ministry of Health. 2006. Tobacco Trends 2006: Monitoring tobacco use in New Zealand. Wellington: Ministry of Health. Available online at: C2E55DCC 2572450013FE5E?Open Accessed 14 February 2007.
  45. Nakamura M, Oshima A, Fujimoto Y, et al. Efficacy and tolerability of varenicline, an alpha4 beta2 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.
  46. Malcolm RE, Sillett RW, Turner JA, et al. The use of nicotine chewing gum as an aid to stopping smoking. Psychopharmacology (Berl) 1980;70:295-296.
  47. Nides M, Oncken C, Gonzales D, et al. Smoking cessation with Varenicline, a selective alpha4 beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placeboand Bupropion-controlled trial with 1-year follow-up. Arch Intern Med 2006;166:1561-1518.
  48. Oncken C, Gonzales D, Nides M, et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, Varenicline, for smoking cessation.
  49. Peto R, Lopez AD, Boreham J, Thun M, Heath C Jr, Doll R: Mortality from smoking worldwide. Br Med Bull 1996;52:12-21.
  50. Paoletti P, Fornai E, Maggiorelli F, et al. Importance of baseline cotinine plasma values in smoking cessation: results from a double- blind study with nicotine patch. Eur Respir J 1996;9:643-651.
  51. Randomized trial of nicotine patches in general practice: results at one year. Imperial Cancer Research Fund General Practice Research Group. BMJ 1994;308:1476-1477.
  52. Richmond RL, Harris K, de Almeida NA. The transdermal nicotine patch: results of a randomised placebo-controlled trial. Med J Aust 1994;161:130-135.
  53. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004;3:CD000146.
  54. Stapleton J. Cigarette smoking prevalence, cessation and relapse. Stat Meth Med Res 1998;7187-7203.
  55. Schneider NG, Jarvik ME, Forsythe AB, et al. Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial. Addict Behav 1983;8:253-261.
  56. Stapleton JA, Russell MA, Feyerabend C, et al. Dose effects and predictors of outcome in a randomized trial of transdermal nicotine patches in general practice. Addiction 1995;90:31.
  57. Sachs DP, Sawe U, Leischow SJ. Effectiveness of a 16-hour transdermal nicotine patch in a medical practice setting, without intensive group counseling. Arch Intern Med 1993;153:1881-90.
  58. Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR: Effect of maintenance therapy with Varenicline on smoking cessation: a randomized controlled trial. Jama 2006, 296:64-71. Arch Intern Med 2006;166:1571-1517.
  59. Tonnesen P, Fryd V, Hansen M, et al. Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. N Engl J Med 1988;318:15-18.
  60. Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 1999;13:238-246.
  61. Transdermal nicot ine for smoking cessat ion. Sixmonth results from two multicenter controlled clinical trials. Transdermal Nicotine Study Group. JAMA 1991;266:3133-3138.
  62. Tonnesen P, Norregaard J, Simonsen K, et al. A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation. N Engl J Med 1991;325:311-315.
  63. Westman EC, Levin ED, Rose JE. The nicotine patch in smoking cessation. A randomized trial with telephone counseling. Arch Intern Med 1993;153:1917-1923.
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