Abstract Background
Cigarette smoking is one of the leading causes of early death. UK-licensed stop-smoking medicines include Varenicline [Champix], Bupropion [Zyban], Nicotine Replacement Therapy [NRT], and one electronic cigarette (E-cigarette) model; however, there is ongoing debate regarding their neuropsychiatric safety.Methodology: We conducted systematic reviews and network meta-analyses of RCTs of medicines delivered as monotherapy and in combination treatment (e.g. Varenicline+NRT) with control groups. Studies published before March 2017 were identified from 8 databases. The primary composite safety outcome was serious adverse events (SAEs) and secondary composite outcomes were major adverse neuropsychiatric events (MANEs) and major adverse cardiovascular events (MACEs). The primary effectiveness outcome was sustained smoking cessation abstinence (≥ 6 months, bio-verified).
Results
We screened 10,779 records and analysed 334 and 346 RCTs for safety and effectiveness outcomes, respectively. We found that Bupropion increased the odds of SAEs (OR=1.31, 95% CI 1.06-1.60) but reduced the odds of MANEs (0.62, 0.42-0.87) compared to placebo, whereas E-Cigarette increased odds of SAEs compared to placebo (2.34, 1.09-5.16). No treatment increased the odds of MACEs compared to placebo. Regarding effectiveness, smokers randomised to Bupropion (1.65, 1.39-1.95), Varenicline (2.75, 2.29 to 3.29), Varenicline+NRT (5.58, 2.25-14.0) or Varenicline+Bupropion (2.80, 1.15-6.96), alongside E-Cigarette users (2.75, 1.26-6.11), were more likely to achieve sustained abstinence than smokers treated with placebo.
Conclusions
Combination treatment with varenicline and NRT (unlicensed in the UK) is most likely to be effective at achieving sustained abstinence from smoking. E-cigarettes for smoking cessation showed promise, but increased odds for a SAE based on few studies. External funding details This project presents independent research which was funded by the National Institute for Health Research Health Technology Assessment Programme (project number NIHR HTA 15/58/18).