Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta-analysis of randomized controlled trials

Kyla H. Thomas, Michael N. Dalili, José A. López-López, Edna Keeney, David M. Phillippo, Marcus R. Munafò, Matt Stevenson, Deborah M. Caldwell, Nicky J. Welton

Research output: Contribution to journalReview articlepeer-review

33 Citations (SciVal)

Abstract

Aim: To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety. 

Method: Systematic reviews and Bayesian network meta-analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e-cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow-up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta-regression to explore covariates. 

Results: We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34–3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27–14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second-best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04–1.58), and we found no evidence of effect modification. 

Conclusions: Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.

Original languageEnglish
Pages (from-to)861-876
Number of pages16
JournalAddiction
Volume117
Issue number4
Early online date11 Oct 2021
DOIs
Publication statusPublished - 30 Apr 2022

Funding

The study was funded by the NIHR Health Technology Assessment programme (project number 15/58/18). This publication presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. J.L.L.’s time was also funded by a grant from the Spanish Government (Ministerio de Ciencia e Innovación, project number PID2019-104033GA-I00). The authors acknowledge Professor David Gunnell for help with preparing the original project proposal and grant submission, Sarah Dawson and Cath Borwick for help with designing and running search strategies and Olivia Crane and the Public Health Internal Guideline Development team at the National Institute for Health and Care Excellence (NICE) for their collaboration.

Keywords

  • adverse events
  • bupropion
  • effectiveness
  • electronic cigarettes
  • network meta-analysis
  • nicotine replacement therapy
  • safety
  • smoking
  • varenicline

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

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