8,882
Views
29
CrossRef citations to date
0
Altmetric
Addiction Medicine

Varenicline: mode of action, efficacy, safety and accumulated experience salient for clinical populations

, , , , , , , & show all
Pages 713-730 | Received 31 Jul 2019, Accepted 11 Feb 2020, Published online: 14 Mar 2020

References

  • Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224–2260.
  • Hughes JR, Stead LF, Lancaster T. Anxiolytics for smoking cessation. Cochrane Database Syst Rev. 2000;(4):CD002849.
  • Fernö O, Lichtneckert SJA, Lundgren CEG. A substitute for tobacco smoking. Psychopharmacologia. 1973;31(3):201–204.
  • Fagerström KO. A comparison of psychological and pharmacological treatment in smoking cessation. J Behav Med. 1982;5(3):343–351.
  • Ferry LH, Burchette RJ. Efficacy of bupropion for smoking cessation in nondepressed smokers. J Addict Dis. 1994;13:249.
  • Hughes J, Stead L, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2004;(4):CD000031.
  • Silagy C, Lancaster T, Stead L. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2004;(3):CD000146.
  • Cohen C, Bergis OE, Galli F, et al. SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation. J Pharmacol Exp Ther. 2003;306(1):407–420.
  • Coe JW, Vetelino MG, Bashore CG, et al. In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine. Bioorg Med Chem Lett. 2005;15(12):2974–2979.
  • Coe JW, Brooks PR, Vetelino MG, et al. Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation. J Med Chem. 2005;48(10):3474–3477.
  • Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296(1):47–55.
  • Jorenby DE, Hays JT, Rigotti NA, et al. 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(1):56–63.
  • Cahill K, Ussher MH. Cannabinoid type 1 receptor antagonists for smoking cessation. Cochrane Database Syst Rev. 2011;(3):CD005353.
  • Goniewicz ML, Delijewski M. Nicotine vaccines to treat tobacco dependence. Hum Vaccin Immunother. 2013;9(1):13–25.
  • Brunzell DH. Preclinical evidence that activation of mesolimbic alpha 6 subunit containing nicotinic acetylcholine receptors supports nicotine addiction phenotype. Nicotine Tob Res. 2012;14(11):1258–1269.
  • Rollema H, Chambers LK, Coe JW, et al. Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology. 2007;52(3):985–994.
  • Rollema H, Hurst RS. The contribution of agonist and antagonist activities of alpha4beta2* nAChR ligands to smoking cessation efficacy: a quantitative analysis of literature data. Psychopharmacology (Berl). 2018;235(9):2479–2505.
  • West R, Baker CL, Cappelleri JC, et al. Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt. Psychopharmacology (Berl). 2008;197(3):371–377.
  • Foulds J, Russ C, Yu CR, et al. Effect of varenicline on individual nicotine withdrawal symptoms: a combined analysis of eight randomized, placebo-controlled trials. Nicotine Tob Res. 2013;15(11):1849–1857.
  • Ravva P, Gastonguay MR, Faessel HM, et al. Pharmacokinetic-pharmacodynamic modeling of the effect of varenicline on nicotine craving in adult smokers. Nicotine Tob Res. 2015;17(1):106–113.
  • Brandon TH, Drobes DJ, Unrod M, et al. Varenicline effects on craving, cue reactivity, and smoking reward. Psychopharmacology (Berl). 2011;218(2):391–403.
  • Obach RS, Reed-Hagen AE, Krueger SS, et al. Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006;34(1):121–130.
  • Faessel HM, Smith BJ, Gibbs MA, et al. Single-dose pharmacokinetics of varenicline, a selective nicotinic receptor partial agonist, in healthy smokers and nonsmokers. J Clin Pharmacol. 2006;46(9):991–998.
  • Burstein AH, Fullerton T, Clark DJ, et al. Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers. J Clin Pharmacol. 2006;46(11):1234–1240.
  • Faessel HM, Obach RS, Rollema H, et al. A review of the clinical pharmacokinetics and pharmacodynamics of varenicline for smoking cessation. Clin Pharmacokinet. 2010;49(12):799–816.
  • Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.
  • Chantix (varenicline tartrate) prescribing information [Internet]. Pfizer Inc.; 2018. [updated 2018 June; cited 2019 Jan 30]. Available from: http://labeling.pfizer.com/showlabeling.aspx?id=557
  • Bolliger CT, Issa JS, Posadas-Valay R, et al. Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2011;33(4):465–477.
  • Nakamura M, Oshima A, Fujimoto Y, et al. Efficacy and tolerability of varenicline, an alpha4beta2 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(6):1040–1056.
  • Tsai ST, Cho HJ, Cheng HS, et al. A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clin Ther. 2007;29(6):1027–1039.
  • Wang C, Xiao D, Chan KP, et al. Varenicline for smoking cessation: a placebo-controlled, randomized study. Respirology. 2009;14(3):384–392.
  • Nides M, Glover ED, Reus VI, et al. Varenicline versus bupropion SR or placebo for smoking cessation: a pooled analysis. Am J Health Behav. 2008;32(6):664–675.
  • Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387(10037):2507–2520.
  • Mills EJ, Wu P, Lockhart I, et al. Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis. Ann Med. 2012;44(6):588–597.
  • 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.
  • Cahill K, Lindson-Hawley N, Thomas KH, et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2016;(5):CD006103.
  • Tashkin DP, Rennard S, Hays JT, et al. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest. 2011;139(3):591–599.
  • Jimenez Ruiz CA, Ramos Pinedo A, Cicero Guerrero A, et al. Characteristics of COPD smokers and effectiveness and safety of smoking cessation medications. Nicotine Tob Res. 2012;14(9):1035–1039.
  • Rigotti NA, Pipe AL, Benowitz NL, et al. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation. 2010;121(2):221–229.
  • Eisenberg MJ, Windle SB, Roy N, et al. Varenicline for smoking cessation in hospitalized patients with acute coronary syndrome. Circulation. 2016;133(1):21–30.
  • Windle SB, Dehghani P, Roy N, et al. Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital. CMAJ. 2018;190(12):E347–E354.
  • Peckham E, Brabyn S, Cook L, et al. Smoking cessation in severe mental ill health: what works? an updated systematic review and meta-analysis. BMC Psychiatry. 2017;17(1):252.
  • Weiner E, Buchholz A, Coffay A, et al. Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res. 2011;129(1):94–95.
  • Williams JM, Anthenelli RM, Morris CD, et al. A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2012;73(05):654–660.
  • Anthenelli RM, Morris C, Ramey TS, et al. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med. 2013;159(6):390–400.
  • Ahmed S, Virani S, Kotapati VP, et al. Efficacy and safety of varenicline for smoking cessation in schizophrenia: a meta-analysis. Front Psychiatry. 2018;9:428
  • Tonstad S, Tønnesen P, Hajek P, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA. 2006;296(1):64–71.
  • Hajek P, Tønnesen P, Arteaga C, et al. Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment. Addiction. 2009;104(9):1597–1602.
  • 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(2):145–154.
  • Hajek P, McRobbie HJ, Myers KE, et al. 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.
  • Hawk LW, Jr., Ashare RL, Lohnes SF, et al. The effects of extended pre-quit varenicline treatment on smoking behavior and short-term abstinence: a randomized clinical trial. Clin Pharmacol Ther. 2012;91(2):172–180.
  • Rennard S, Hughes J, Cinciripini PM, et al. A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Nicotine Tob Res. 2012;14(3):343–350.
  • Ebbert JO, Hughes JR, West RJ, et al. Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial. JAMA. 2015;313(7):687–694.
  • Nakamura M, Abe M, Ohkura M, et al. Efficacy of varenicline for cigarette reduction before quitting in Japanese smokers: a subpopulation analysis of the Reduce to Quit trial. Clin Ther. 2017;39(4):863–872.
  • Oncken C, Gonzales D, Nides M, et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006;166(15):1571–1577.
  • Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med. 2006;166(15):1561–1568.
  • Niaura R, Hays JT, Jorenby DE, et al. The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial. Curr Med Res Opin. 2008;24(7):1931–1941.
  • Faessel HM, Gibbs MA, Clark DJ, et al. Multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy smokers. J Clin Pharmacol. 2006;46(12):1439–1448.
  • Hajek P, McRobbie H, Myers Smith K, et al. Increasing varenicline dose in smokers who do not respond to the standard dosage: a randomized clinical trial. JAMA Intern Med. 2015;175(2):266–271.
  • Jiménez-Ruiz CA, Barrios M, Peña S, et al. Increasing the dose of varenicline in patients who do not respond to the standard dose. Mayo Clin Proc. 2013;88(12):1443–1445.
  • Karam-Hage M, Kypriotakis G, Robinson JD, et al. Improvement of smoking abstinence rates with increased varenicline dosage: a propensity score-matched analysis. J Clin Psychopharmacol. 2018;38(1):34–41.
  • Gonzales D, Hajek P, Pliamm L, 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.
  • West R, Evins AE, Benowitz NL, et al. Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES. Addiction. 2018;113(8):1507–1516.
  • Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2008;(1):CD000146.
  • Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2011;(2):CD006103.
  • Hajek P, Smith KM, Dhanji AR, et al. Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? A randomised controlled trial. BMC Med. 2013;11(1):140.
  • Ramon JM, Morchon S, Baena A, et al. Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation. BMC Med. 2014;12(1):172.
  • Koegelenberg CF, Noor F, Bateman ED, 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.
  • Preloading Investigators. Effects on abstinence of nicotine patch treatment before quitting smoking: parallel, two arm, pragmatic randomised trial. BMJ. 2018;361:k2164.
  • Hajek P, Corbin L, Ladmore D, et al. Adding E-cigarettes to specialist stop-smoking treatment: City of London Pilot Project. J Addict Res Ther. 2015;6:244.
  • 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(2):155–163.
  • Rose JE, Behm FM. Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. AJP. 2014;171(11):1199–1205.
  • Cinciripini PM, Minnix JA, Green CE, et al. An RCT with the combination of varenicline and bupropion for smoking cessation: clinical implications for front line use. Addiction. 2018;113(9):1673–1682.
  • Fagerström K, Russ C, Yu CR, et al. The Fagerstrom Test for Nicotine Dependence as a predictor of smoking abstinence: a pooled analysis of varenicline clinical trial data. Nicotine Tob Res. 2012;14(12):1467–1473.
  • Scharf D, Shiffman S. Are there gender differences in smoking cessation, with and without bupropion? Pooled- and meta-analyses of clinical trials of Bupropion SR. Addiction. 2004;99(11):1462–1469.
  • Jarvis MJ, Cohen JE, Delnevo CD, et al. Dispelling myths about gender differences in smoking cessation: population data from the USA, Canada and Britain. Tob Control. 2013;22(5):356–360.
  • McKee SA, Smith PH, Kaufman M, et al. Sex differences in varenicline efficacy for smoking cessation: a meta-analysis. NICTOB. 2016;18(5):1002–1011.
  • Smith PH, Weinberger AH, Zhang J, et al. Sex differences in smoking cessation pharmacotherapy comparative efficacy: a network meta-analysis. Nicotine Tob Res. 2017;19(3):273–281.
  • Tonstad S. Smoking cessation efficacy and safety of varenicline, an alpha4beta2 nicotinic receptor partial agonist. J Cardiovasc Nurs. 2006;21(6):433–436.
  • Benowitz NL, Pipe A, West R, et al. Cardiovascular safety of varenicline, bupropion, and nicotine patch in smokers: a randomized clinical trial. JAMA Intern Med. 2018;178(5):622–631.
  • 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(12):1359–1366.
  • Ware JH, Vetrovec GW, Miller AB, et al. Cardiovascular safety of varenicline: patient-level meta-analysis of randomized, blinded, placebo-controlled trials. Am J Ther. 2013;20(3):235–246.
  • 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–e2856.
  • Mills EJ, Thorlund K, Eapen S, et al. Cardiovascular events associated with smoking cessation pharmacotherapies: a network meta-analysis. Circulation. 2014;129(1):28–41.
  • Sterling LH, Windle SB, Filion KB, et al. Varenicline and adverse cardiovascular events: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5(2):e002849.
  • 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.
  • Graham DJ, By K, McKean S, et al. Cardiovascular and mortality risks in older Medicare patients treated with varenicline or bupropion for smoking cessation: an observational cohort study. Pharmacoepidemiol Drug Saf. 2014;23(11):1205–1212.
  • Kotz D, Viechtbauer W, Simpson C, et al. Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study. Lancet Respir Med. 2015;3(10):761–768.
  • Wu Q, Gilbody S, Peckham E, et al. Varenicline for smoking cessation and reduction in people with severe mental illnesses: systematic review and meta-analysis. Addiction. 2016;111(9):1554–1567.
  • Roberts E, Eden Evins A, McNeill A, et al. Efficacy and tolerability of pharmacotherapy for smoking cessation in adults with serious mental illness: a systematic review and network meta-analysis. Addiction. 2016;111(4):599–612.
  • Kishi T, Iwata N. Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci. 2015;265(3):259–268.
  • 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–h1109.
  • Gibbons RD, Mann JJ. Varenicline, smoking cessation, and neuropsychiatric adverse events. AJP. 2013;170(12):1460–1467.
  • Huang Y, Li W, Yang L, et al. Long-term efficacy and safety of varenicline for smoking cessation: a systematic review and meta-analysis of randomized controlled trials. J Public Health. 2012;20(4):355–365.
  • Tonstad S, Davies S, Flammer M, et al. Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Drug Saf. 2010;33(4):289–301.
  • Cunningham FE, Hur K, Dong D, et al. A comparison of neuropsychiatric adverse events during early treatment with varenicline or a nicotine patch. Addiction. 2016;111(7):1283–1292.
  • Molero Y, Lichtenstein P, Zetterqvist J, et al. Varenicline and risk of psychiatric conditions, suicidal behaviour, criminal offending, and transport accidents and offences: population based cohort study. BMJ. 2015;350:h2388–h2388.
  • Pasternak B, Svanstrom H, Hviid A. Use of varenicline versus bupropion and risk of psychiatric adverse events. Addiction. 2013;108(7):1336–1343.
  • 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–f5704.
  • Meyer TE, Taylor LG, Xie S, et al. Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System. Addiction. 2013;108(1):203–210.
  • FDA Drug Safety Communication: Safety review update of Chantix (varenicline) and risk of neuropsychiatric adverse events [Internet]. U.S. Food and Drug Administration; 2011 [updated 2011 Oct 24; cited 2014 Aug 31]. Available from: http://www.fda.gov/drugs/drugsafety/ucm276737.htm
  • Gunnell D, Irvine D, Wise L, et al. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ. 2009;339:b3805–b3805.
  • Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 2008;35(2):158–176.
  • Chengappa KN, Perkins KA, Brar JS, et al. Varenicline for smoking cessation in bipolar disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2014;75(07):765–772.
  • Ashare RL, Tang KZ, Mesaros AC, et al. Effects of 21 days of varenicline versus placebo on smoking behaviors and urges among non-treatment seeking smokers. J Psychopharmacol. 2012;26(10):1383–1390.
  • Tonnesen P, Mikkelsen K. Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. Nicotine Tob Res. 2013;15(2):419–427.
  • Plebani JG, Lynch KG, Yu Q, et al. Results of an initial clinical trial of varenicline for the treatment of cocaine dependence. Drug Alcohol Depend. 2012;121(1–2):163–166.
  • Litten RZ, Ryan ML, Fertig JB, et al. A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med. 2013;7(4):277–286.
  • Oon-Arom A, Likhitsathain S, Srisurapanont M. Efficacy and acceptability of varenicline for alcoholism: a systematic review and meta-analysis of randomized-controlled trials. Drug Alcohol Depend. 2019;205:107631.
  • Evins AE, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with psychotic, anxiety, and mood disorders in the EAGLES trial. J Clin Psychopharmacol. 2019;39(2):108–116.