Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial

Nicotine Tob Res. 2013 Feb;15(2):419-27. doi: 10.1093/ntr/nts146. Epub 2012 Sep 27.


Introduction: This study evaluated the effect of varenicline in combination with counseling to assist long-term nicotine replacement therapy (NRT) users to quit NRT.

Methods: This was a double-blind, placebo-controlled, randomized trial of varenicline or placebo for 12 weeks, with 52-week follow-up, performed in 1 hospital-based smoking cessation specialist clinic. At the first visit, 139 ex-smokers and long-term NRT users were allocated to treatment according to a computer-generated list with random numbers. Visits were scheduled at Weeks 0, 2, 4, 6, 9, 12, and 52. At each visit, nurse-led counseling was delivered, carbon monoxide in expired air, plasma cotinine, and body weight were assessed, and subjects were asked about craving, nausea, and dreams. The primary outcome was 12-week point prevalence quit rate (PPR) of nicotine replacement therapy use.

Results: At all time points, the PPR was superior for varenicline versus placebo, although the difference was only statistically significant at 12 and 36 weeks. The PPR was 64.3% (varenicline) versus 40.6% (placebo) at 12 weeks (p = .006), and 42.9% (varenicline) versus 36.2% (placebo) at 52 weeks (NS). The continuous abstinence rate from Week 9 to Week 12 was 48.6 % (varenicline) versus 30.4 % (placebo) (p = .03). Withdrawal symptoms were statistically significantly lower in the varenicline group than the placebo group.

Conclusion: Varenicline for 12 weeks combined with supportive visits was superior to placebo to get long-term NRT users to quit NRT. A larger study is needed to evaluate long-term efficacy.

Trial registration: NCT00977249.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Body Weight
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotinic Antagonists / adverse effects
  • Nicotinic Antagonists / therapeutic use*
  • Placebos
  • Quinoxalines / adverse effects
  • Quinoxalines / therapeutic use*
  • Smoking Cessation*
  • Substance Withdrawal Syndrome
  • Surveys and Questionnaires
  • Varenicline


  • Benzazepines
  • Nicotinic Antagonists
  • Placebos
  • Quinoxalines
  • Nicotine
  • Varenicline

Associated data