title: Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Smoking is a major preventable cause of morbidity and premature death worldwide. Both varenicline and nicotine replacement therapy (NRT) help achieve smoking cessation. However, limited evidence exists regarding whether combination of varenicline and NRT is more effective than either alone. The aim of this research was to investigate the efficacy and safety of varenicline combined with NRT.
  
  
  METHODS
  A systematic search of MEDLINE, EMBASE, ClinicalTrial.gov, and Cochrane Library was conducted in November 2014. Two authors independently reviewed and selected randomized controlled trials. The quality of the studies was evaluated by the Jadad score. We carried out meta-analysis of both early (abstinence rate assessed before or at the end of treatment) and late (assessed after the end of the treatment) outcomes.
  
  
  RESULTS
  Three randomized controlled trials with 904 participants were included in this meta-analysis. All three were comparing combination therapy with varenicline therapy alone. The late outcomes were assessed in 2 of the 3 trials. Both the early and late outcomes were favorable for combination therapy (OR = 1.50, 95 % CI 1.14 to 1.97; OR = 1.62, 95 % CI 1.18 to 2.23, respectively). However, this significance diminished after eliminating a study with pre-cessation treatment using nicotine patch. The most common adverse events were nausea, insomnia, abnormal dreams, and headache. One study reported more skin reactions (14.4 % vs 7.8 %; p = 0.03) associated with combination therapy.
  
  
  CONCLUSIONS
  Combination therapy is more effective than varenicline alone, especially if pre-cessation treatment of nicotine patch is administrated. Adverse events of combination therapy are similar to mono-therapy except for skin reactions.
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. beansheep@gmail.com.|Department of Community and Family Medicine, National Taiwan University Hospital Hsin-Chu Branch, 25, Lane 442, Sec. 1, Jingguo Rd., Hsinchu, 30059, Taiwan. beansheep@gmail.com.
authors.forename: Ping-Hsun
authors.initials: PH
authors.lastname: Chang
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. jiansie@ntu.edu.tw.|Department of Family Medicine, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. jiansie@ntu.edu.tw.|Department of Community and Family Medicine, National Taiwan University Hospital Yun-Lin Branch, 579, Sec. 2, Yunlin Road, Yunlin, 640, Taiwan. jiansie@ntu.edu.tw.
authors.forename: Chien-Hsieh
authors.initials: CH
authors.lastname: Chiang
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. heweiche@gmail.com.
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Ho
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. angie_wu101@hotmail.com.
authors.forename: Pei-Zu
authors.initials: PZ
authors.lastname: Wu
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. jawshiun@ntu.edu.tw.|Department of Family Medicine, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. jawshiun@ntu.edu.tw.
authors.forename: Jaw-Shiun
authors.initials: JS
authors.lastname: Tsai
authors.affiliation: Department of Family Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. fjguo1@ntu.edu.tw.|Department of Family Medicine, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei, 10016, Taiwan. fjguo1@ntu.edu.tw.
authors.forename: Fei-Ran
authors.initials: FR
authors.lastname: Guo
mesh_terms: D004359:Drug Therapy, Combination; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices; D000068580:Varenicline / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000068580:Varenicline