The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: A randomized controlled trial

Raymond Niaura, J. Taylor Hays, Douglas E. Jorenby, Frank T. Leone, John E. Pappas, Karen R. Reeves, Kathryn E. Williams, Clare B. Billing

Research output: Contribution to journalArticlepeer-review


Objective: To determine whether self-regulated flexible dosing with varenicline tartrate is safe and effective for smoking cessation. Research design and methods: 320 healthy, motivated-to-quit smokers (≥10 cigarettes/day) aged 18-65 years, entered a multicenter, randomized, double-blind, placebo-controlled study - conducted between December 26, 2001 and June 24, 2003 - with a 12-week treatment phase and 40-week, double-blind, non-treatment follow-up. Treatment consisted of varenicline or placebo in fixed doses (Week 1: titrated from 0.5 to 1.0 mg/day) followed by a self-regulated flexible schedule (Weeks 2-12: 0.5-2.0 mg/day). Main outcome measures: Primary outcomes included carbon monoxide-confirmed continuous abstinence rate (CAR) from smoking for Weeks 4 through 7, 9 through 12, and 9 through 52. Secondary outcomes included CAR from Weeks 9 through 24, 7-day point prevalence of abstinence, safety assessments, and measures of craving, withdrawal, and smoking reward. Results: Superior CARs were observed in varenicline-treated (n = 157) versus placebo participants (n = 155) for Weeks 4 through 7 (38.2 vs. 11.6%), 9 through 12 (40.1 vs. 11.6%), 9 through 24 (28.0 vs. 9.0%), and 9 through 52 (22.3 vs. 7.7%) (all p < 0.001). Seven-day point prevalence was higher in varenicline-treated than placebo participants at Weeks 12 (46.5 vs. 14.2%; p < 0.001), 24 (32.5 vs. 13.5%; p < 0.001), and 52 (28.0 vs. 13.5%; p = 0.001). Overall, medication compliance was high, although varenicline-treated, but not placebo, participants tended to taper down their dosage over time. Total treatment-emergent AEs were 77.1% (varenicline: 121/157) and 65.8% (placebo: 102/155). Few AEs led to treatment discontinuation (varenicline: 11/157, 7.0% and placebo: 7/155, 4.5%). Participants were primarily healthy Caucasians, so more research is necessary to determine how applicable these findings are to other populations. Conclusions: A self-regulated, flexible dosing regimen of varenicline is well tolerated, with superior effectiveness versus placebo for smoking cessation.

Original languageEnglish (US)
Pages (from-to)1931-1941
Number of pages11
JournalCurrent Medical Research and Opinion
Issue number7
StatePublished - Jul 2008


  • Drug therapy
  • Partial agonist
  • Smoking cessation
  • Varenicline

ASJC Scopus subject areas

  • General Medicine


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