title: A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates.
abstract: BACKGROUND
  Current smoking cessation guidelines recommend setting a quit date prior to starting pharmacotherapy. However, providing flexibility in the date of quitting may be more acceptable to some smokers. The objective of this study was to compare varenicline 1 mg twice daily (b.i.d.) with placebo in subjects using a flexible quit date paradigm after starting medication.
  
  
  METHODS
  In this double-blind, randomized, placebo-controlled international study, smokers of ≥10 cigarettes/day, aged 18-75 years, and who were motivated to quit were randomized (3:1) to receive varenicline 1 mg b.i.d. or placebo for 12 weeks. Subjects were followed up through Week 24. Subjects were instructed to quit between Days 8 and 35 after starting medication. The primary endpoint was carbon monoxide-confirmed continuous abstinence during Weeks 9-12, and a key secondary endpoint was continuous abstinence during Weeks 9-24.
  
  
  RESULTS
  Overall, 493 subjects were randomized to varenicline and 166 to placebo. Continuous abstinence was higher for varenicline than for placebo subjects at the end of treatment (Weeks 9-12: 53.1% vs. 19.3%; odds ratio [OR] 5.9; 95% CI, 3.7-9.4; p < .0001) and through 24 weeks follow-up (Weeks 9-24: 34.7% vs. 12.7%; OR 4.4; 95% CI, 2.6-7.5; p < .0001). Serious adverse events occurred in 1.2% varenicline (none were psychiatric) and 0.6% placebo subjects. Fewer varenicline than placebo subjects reported depression-related adverse events (2.3% vs. 6.7%, respectively).
  
  
  CONCLUSIONS
  Varenicline 1 mg b.i.d. using a flexible quit date paradigm had similar efficacy and safety compared with previous fixed quit date studies.
authors.affiliation: Division of Pulmonary, Critical Care, Sleep & Allergy, University of Nebraska Medical Center, Omaha, NE 68198-5910, USA. srennard@unmc.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Rennard
authors.forename: John
authors.initials: J
authors.lastname: Hughes
authors.forename: Paul M
authors.initials: PM
authors.lastname: Cinciripini
authors.forename: Eva
authors.initials: E
authors.lastname: Kralikova
authors.forename: Tobias
authors.initials: T
authors.lastname: Raupach
authors.forename: Carmen
authors.initials: C
authors.lastname: Arteaga
authors.forename: Lisa B
authors.initials: LB
authors.lastname: St Aubin
authors.forename: Cristina
authors.initials: C
authors.lastname: Russ
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D011810:Quinoxalines / Q000008:administration & dosage / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline
references.citation: Chest. 2011 Mar;139(3):591-599
references.pmid: 20864613
references.citation: Psychopharmacology (Berl). 2008 Apr;197(3):371-7
references.pmid: 18084743
references.citation: Respirology. 2009 Apr;14(3):384-92
references.pmid: 19192221
references.citation: Nicotine Tob Res. 2009 Sep;11(9):1067-75
references.pmid: 19567826
references.citation: Am J Prev Med. 2008 Feb;34(2):102-11
references.pmid: 18201639
references.citation: J Med Chem. 2005 May 19;48(10):3474-7
references.pmid: 15887955
references.citation: Clin Ther. 2007 Jun;29(6):1040-56
references.pmid: 17692720
references.citation: Circulation. 2010 Jan 19;121(2):221-9
references.pmid: 20048210
references.citation: Arch Intern Med. 2006 Aug 14-28;166(15):1571-7
references.pmid: 16908789
references.citation: Addiction. 2004 Jan;99(1):29-38
references.pmid: 14678060
references.citation: Drug Alcohol Depend. 2010 Sep 1;111(1-2):105-13
references.pmid: 20537810
references.citation: JAMA. 2006 Jul 5;296(1):47-55
references.pmid: 16820546
references.citation: Nurs Ethics. 2002 Jan;9(1):105-9
references.pmid: 16010903
references.citation: J Gen Intern Med. 2001 Sep;16(9):606-13
references.pmid: 11556941
references.citation: Clin Ther. 2007 Jun;29(6):1027-39
references.pmid: 17692719
references.citation: Am J Psychiatry. 2007 Jul;164(7):1035-43
references.pmid: 17606655
references.citation: Thorax. 2003 Jun;58(6):484-8
references.pmid: 12775857
references.citation: JAMA. 2006 Jul 5;296(1):56-63
references.pmid: 16820547
references.citation: Am J Prev Med. 2009 Feb;36(2):96-104.e1
references.pmid: 19135903