Looking ahead
Several novel pharmacotherapies have been evaluated for smoking cessation in recent years. Among them is a nicotine vaccine that several drug companies have been pursuing. In theory, such a vaccine would create an immunologic reaction to nicotine in a smoker, thereby preventing the substance from reaching the brain and providing rewarding stimuli. A 2008 Cochrane review of four trials assessing the efficacy of nicotine vaccines for tobacco cessation found that none showed efficacy.34
Naltrexone, an opioid antagonist, has shown efficacy in helping those with opioid or alcohol dependence achieve abstinence from these substances, raising the possibility that it might aid in smoking cessation as well. A 2013 Cochrane review of eight trials found that this was not the case: Compared with placebo, naltrexone was not beneficial when used alone (RR, 1.00) or as an adjunct to NRT compared with NRT alone (RR, 0.95).35
Cytisine, an extract from plants in the Faboideae family, has been used in Eastern Europe for decades for smoking cessation. It appears to work as a nicotine receptor partial agonist similar to varenicline. The extract does not have FDA approval, but the National Institutes of Health’s Center for Complementary and Integrative Health is sponsoring early-stage safety trials that could lead to its approval in the US.36
A 2012 Cochrane review identified two recent RCTs evaluating cytisine and found it to be effective in increasing smoking cessation rates, compared with placebo (RR, 3.98).13
The authors thank Matt Orr, PhD, and Kathryn E. Bornemann for their help with this manuscript.
References
1. National Center for Chronic Disease Prevention and Health Promotion Office on Smoking and Health. The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General. www.ncbi.nlm.nih.gov/pubmed/24455788. Accessed January 21, 2016.
2. Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008;57:1226-1228.
3. Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ. 2004;328:1519.
4. US Public Health Service. A clinical practice guideline for treating tobacco use and dependence: 2008 update. Am J Prev Med. 2008;35:158-176.
5. US Preventive Services Task Force. Tobacco use in adults and pregnant women: counseling and interventions. April 2009. www.uspreventiveservicestaskforce.org/Page/Topic/recommendation-summary/tobacco-use-in-adults-and-pregnant-women-counseling-and-interventions. Accessed January 21, 2016.
6. Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031.
7. Cahill K, Stevens S, Perera R, et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013;(5):CD009329.
8. Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2012;(11):CD000146.
9. Schnoll RA, Goelz PM, Veluz-Wilkins A, et al. Long-term nicotine replacement therapy: a randomized clinical trial. JAMA Intern Med. 2015;175: 504-511.
10. Coleman T, Chamberlain C, Davey MA, et al. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2012;(9):CD010078.
11. 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.
12. Eisenberg MJ, Filion KB, Yavin D, et al. Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CMAJ. 2008;179:135-144.
13. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2012;(4):CD006103.
14. Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313:687-694.
15. FDA. Reports of suicidality associated with use of varenicline (marketed as CHANTIX) and bupropion (marketed as ZYBAN and GENERICS). FDA Drug Safety News. 2009.
16. Moore TJ, Furberg CD, Glenmullen J, et al. Suicidal behavior and depression in smoking cessation treatments. PLoS One. 2011;6:e27016.
17. Thomas KH, Martin RM, Davies NM, et al. Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study. BMJ. 2013;347:f5704.
18. Thomas KH, Martin RM, Knipe DW, et al. Risk of neuropsychiatric adverse events associated with varenicline: systematic review and meta-analysis. BMJ. 2015;350:h1109.
19. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014;311:145-154.
20. Singh S, Loke YK, Spangler JG, et al. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011;183:1359-1366.
21. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ. 2012;344:e2856.
22. Svanström H, Pasternak B, Hviid A. Use of varenicline for smoking cessation and risk of serious cardiovascular events: nationwide cohort study. BMJ. 2012;345:e7176.
23. Smith SS, McCarthy DE, Japuntich SJ, et al. Comparative effectiveness of five smoking cessation pharmacotherapies in primary care clinics. Arch Intern Med. 2009;169:2148-2155.
24. Koegelenberg CFN, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation. JAMA. 2014;312:155-161.
25. Ebbert JO, Hatsukami DK, Croghan IT, et al. Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial. JAMA. 2014;311:155-163.
26. Steinberg MB, Greenhaus S, Schmelzer AC, et al. Triple-combination pharmacotherapy for medically ill smokers: a randomized trial. Ann Intern Med. 2009;150:447-454.
27. McMillen RC, Gottlieb MA, Shaefer RMW, et al. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 2015;17:1195-1202.
28. McRobbie H, Bullen C, Hartmann-Boyce J, et al. Electronic cigarettes for smoking cessation and reduction. Cochrane Database Syst Rev. 2014;(12):CD010216.
29. Brose LS, Hitchman SC, Brown J, et al. Is the use of electronic cigarettes while smoking associated with smoking cessation attempts, cessation and reduced cigarette consumption? A survey with a 1-year follow-up. Addiction. 2015;110:1160-1168.
30. Adriaens K, Van Gucht D, Declerck P, et al. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11:11220-11248.
31. Goniewicz ML, Knysak J, Gawron M, et al. Levels of selected carcinogens and toxicants in vapour from electronic cigarettes. Tob Control. 2014;23:133-139.
32. Pisinger C, Døssing M. A systematic review of health effects of electronic cigarettes. Prev Med (Baltim). 2014;69C:248-260.
33. Bowerman M. Fla man hospitalized after e-cigarette explodes in face. USA Today Network. October 29, 2015. www.usatoday.com/story/news/nation-now/2015/10/29/fla-man-hospitalized-e-cigarette-explodes-face/74791722/. Accessed January 21, 2016.
34. Hatsukami D, Cahill K, Stead LF. Nicotine vaccines for smoking cessation. Cochrane Database Syst Rev. 2008;(2):CD007072.
35. David SP, Lancaster T, Stead LF, et al. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2013;(6):CD003086.
36. Frankel T. Pill that quashes tobacco urge found in plain sight. Washington Post. May 15, 2015. www.washingtonpost.com/business/economy/pill-promises-a-safercheaper-way-than-chantix-to-quit-smoking/2015/05/15/8ce5590c-f830-11e4-9030-b4732caefe81_story.html. Accessed January 21, 2016.