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 Sep;44(6):588-97. doi: 10.3109/07853890.2012.705016. Epub 2012 Aug 6.


Aim: This review compared the effect of high-dose nicotine replacement therapy (NRT) and combinations of NRT for increasing smoking abstinence rates compared to standard-dose NRT patch, varenicline, and bupropion on smoking abstinence.

Methods: Ten electronic databases were searched (up to January 2012) for randomized controlled trials (RCT) of standard-dose (≤ 22 mg) or high-dose nicotine patch therapy (> 22 mg), combination NRT (e.g. nicotine patch + nicotine inhaler), bupropion, and varenicline. Analysis consisted of random-effects pairwise meta-analysis and a Bayesian multiple treatment comparison (MTC).

Results: We identified 146 RCTs (65 standard-doses of the nicotine patch (≤ 22 mg); 6 high-dose NRT patch (> 22 mg); 5 high versus standard-dose NRT patch; 5 combination NRT versus inert controls; 6 combination versus single NRT patch; 48 bupropion; and 11 varenicline). The MTC found that all therapies offered treatment benefits at most time points over controls. Combination NRT and higher-dose NRT did not demonstrate consistent effects over other interventions. With the exception of varenicline, the benefits of treatments over standard-dose NRT were not retained in the long term.

Conclusions: All pharmacologic treatments were significantly more effective than inert controls. Varenicline was the only treatment demonstrating effects over other options. These results should be considered in the development of clinical practice guidelines.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Benzazepines / administration & dosage*
  • Bupropion / administration & dosage*
  • Bupropion / therapeutic use
  • Databases, Bibliographic
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Humans
  • Nicotinic Antagonists / administration & dosage*
  • Nicotinic Antagonists / therapeutic use
  • Quinoxalines / administration & dosage*
  • Smoking Cessation / methods*
  • Tobacco Use Cessation Devices / statistics & numerical data*
  • Varenicline


  • Benzazepines
  • Nicotinic Antagonists
  • Quinoxalines
  • Bupropion
  • Varenicline