Smoking Cessation With Varenicline, a Selective α4β2 Nicotinic Receptor Partial Agonist: Results From a 7-Week, Randomized, Placebo- and Bupropion-Controlled Trial With 1-Year Follow-up | Lifestyle Behaviors | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Taylor  ALBettcher  DW WHO Framework Convention on Tobacco Control: a global “good” for public health.  Bull World Health Organ 2000;78920- 929PubMedGoogle Scholar
Ezzati  MLopez  AD Estimates of global mortality attributable to smoking in 2000.  Lancet 2003;362847- 852PubMedGoogle ScholarCrossref
Hughes  JRKeely  JNaud  S Shape of the relapse curve and long-term abstinence among untreated smokers.  Addiction 2004;9929- 38PubMedGoogle ScholarCrossref
Hughes  JRStead  LFLancaster  T Antidepressants for smoking cessation.  Cochrane Database Syst Rev 2003; ((2)) CD000031PubMedGoogle Scholar
Silagy  CLancaster  TStead  LMant  DFowler  G Nicotine replacement therapy for smoking cessation.  Cochrane Database Syst Rev 2004; ((3)) CD000146PubMedGoogle Scholar
Hughes  JRStead  LFLancaster  T Nortriptyline for smoking cessation: a review.  Nicotine Tob Res 2005;7491- 499PubMedGoogle ScholarCrossref
Jimenez-Ruiz  CGranda Orive  JI Success rates for nortriptyline.  Chest 2003;124768- 769PubMedGoogle ScholarCrossref
Fiore  MCBailey  WCCohen  SJ  et al.  Treating Tobacco Use and Dependence: Clinical Practice Guideline.  Washington, DC Public Health Service2000;
National Institute for Clinical Excellence, Guidance on the Use of Nicotine Replacement Therapy (NTR) and Bupropion for Smoking Cessation.  Washington, DC: National Institute for Clinical Excellence; March 2002. Technical appraisal report 39
Coe  JWBrooks  PRVetelino  MG  et al.  Varenicline: an α4β2 nicotinic receptor partial agonist for smoking cessation.  J Med Chem 2005;483474- 3477PubMedGoogle ScholarCrossref
Dani  JADe Biasi  M Cellular mechanisms of nicotine addiction.  Pharmacol Biochem Behav 2001;70439- 446PubMedGoogle ScholarCrossref
Picciotto  MRZoli  MRimondini  R  et al.  Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine.  Nature 1998;391173- 177PubMedGoogle ScholarCrossref
Tapper  ARMcKinney  SLNashmi  R  et al.  Nicotine activation of α4* receptors: sufficient for reward, tolerance, and sensitization.  Science 2004;3061029- 1032PubMedGoogle ScholarCrossref
Scharfenberg  GBenndorf  SKempe  G Cytisine (Tabex) as a pharmaceutical aid in stopping smoking [in German].  Dtsch Gesundheitsw 1971;26463- 465PubMedGoogle Scholar
Rose  JEBehm  FMWestman  EC Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy.  Exp Clin Psychopharmacol 1998;6331- 343PubMedGoogle ScholarCrossref
Schuurmans  MMDiacon  AHvan Biljon  XBolliger  CT Effect of pre-treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial.  Addiction 2004;99634- 640PubMedGoogle ScholarCrossref
 Clearing the Air: How to Quit Smoking . . . and Quit for Keeps.  Bethesda, MD National Cancer Institute, National Institutes of Health1993;NIH publication 95-1647
Hughes  JRHatsukami  D Signs and symptoms of tobacco withdrawal.  Arch Gen Psychiatry 1986;43289- 294PubMedGoogle ScholarCrossref
Cox  LSTiffany  STChristen  AG Evaluation of the brief questionnaire of smoking urges (QSU-brief) in laboratory and clinical settings.  Nicotine Tob Res 2001;37- 16PubMedGoogle ScholarCrossref
Cappelleri  JCBushmakin  AGBaker  CLMerikle  EOlufade  AOGilbert  DG Revealing the multidimensional framework of the Minnesota Nicotine Withdrawal Scale.  Curr Med Res Opin 2005;21749- 760PubMedGoogle ScholarCrossref
Hurt  RDSachs  DPGlover  ED  et al.  A comparison of sustained-release bupropion and placebo for smoking cessation.  N Engl J Med 1997;3371195- 1202PubMedGoogle ScholarCrossref
Jorenby  DELeischow  SJNides  MA  et al.  A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.  N Engl J Med 1999;340685- 691PubMedGoogle ScholarCrossref
Tashkin  DKanner  RBailey  W  et al.  Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.  Lancet 2001;3571571- 1575PubMedGoogle ScholarCrossref
Gonzales  DRennard  SINides  MA  et al. Varenicline Phase 3 Study Group, Varenicline, an α4β2 nicotinic acetycholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.  JAMA 2006;29647- 55Google ScholarCrossref
Jorenby  DEHays  JTRigotti  NA  et al. Varenicline Phase 3 Study Group, 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;29656- 63Google ScholarCrossref
Rose  JE Nicotine and nonnicotine factors in cigarette addiction.  Psychopharmacology (Berl) 2006;184274- 285PubMedGoogle ScholarCrossref
Rose  JEBehm  FMWestman  EC Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking.  Pharmacol Biochem Behav 2001;68187- 197PubMedGoogle ScholarCrossref
Tzschentke  TM Behavioral pharmacology of buprenorphine, with a focus on preclinical models of reward and addiction.  Psychopharmacology (Berl) 2002;1611- 16PubMedGoogle ScholarCrossref
Original Investigation
August 14, 2006

Smoking Cessation With Varenicline, a Selective α4β2 Nicotinic Receptor Partial Agonist: Results From a 7-Week, Randomized, Placebo- and Bupropion-Controlled Trial With 1-Year Follow-up

Author Affiliations

Author Affiliations: Los Angeles Clinical Trials, Los Angeles, Calif (Dr Nides); Department of Medicine, University of Connecticut Health Center, Farmington (Dr Oncken); Smoking Cessation Center, Department of Medicine, Oregon Health & Science University, Portland (Dr Gonzales); Pulmonary Division, University of Nebraska Medical Center, Omaha (Dr Rennard); and Pfizer Global Research and Development, Pfizer Global Pharmaceuticals, Groton, Conn (Drs Watsky and Reeves and Mr Anziano).

Arch Intern Med. 2006;166(15):1561-1568. doi:10.1001/archinte.166.15.1561

Background  Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control.

Methods  A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks.

Results  During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide–confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline.

Conclusions  Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.