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Combined Treatments Most Effective for Smoking Cessation, Study Finds

Combination treatment, particularly varenicline and nicotine replacement therapy (NRT), are the most effective tobacco cessation pharmacotherapies, according to the findings of the largest review to examine the effectiveness and safety of e-cigarettes and pharmacological interventions for smoking cessation.

The study, led by the University of Bristol, included systematic reviews and Bayesian network meta-analyses of randomised controlled trials 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 for effectiveness or any duration for safety.

A total of 363 trials for effectiveness and 355 for safety were identified. These showed that most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence. The most effective of these were varenicline standard dose (OR, 2.83; 95% credible interval [CrI], 2.34-3.39) and varenicline standard dose plus standard dose NRT (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. Standard dose varenicline with standard dose NRT showed a high probability of being ranked best or second best.

For safety, only bupropion at standard dose increased the odds of experiencing serious adverse events compared with placebo (OR, 1.27; 95% CrI, 1.04-1.58) but there was no evidence of effect modification.

Co-author, Dr Michael Dalili, senior research associate in public health at the University of Bristol, said: "Our study strengthens the evidence base for the use of varenicline and NRT monotherapies as first line choices for tobacco cessation in line with current NICE recommendations. Our findings should provide reassurance to patients, clinicians, and policy makers about the safety of these treatments."

The findings could have implications for the licensing of smoking cessation treatments, as e-cigarettes and combination therapies are currently unlicensed.

NICE will shortly be releasing new guidance for preventing uptake of tobacco use, promoting quitting and treating dependence. The data from this study will be reviewed as part of the guidance development.

Thomas KH, Dalili MN, López-López JA, Keeney E, Phillippo DM, Munafò MR, Stevenson M, Caldwell DM, Welton NJ. Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta-analysis of randomized controlled trials. Addiction. 2021 Oct 11 [Epub ahead of print]. doi: 10.1111/add.15675. PMID: 34636108