Background Tobacco smoking is the leading preventable cause of death and disease worldwide. Smoking cessation can reduce this harm, and many individuals would like to stop. There are a number of medications licenced globally to help individuals quit, and e‐cigarettes are used for this purpose in many countries. Types of medications include nicotine replacement therapy (NRT), cytisine (e.g., Tabex), varenicline (e.g., Chantix, Champix), bupropion (e.g., Zyban, Wellbutrin), and nortriptyline (e.g., Norpress). Nortriptyline is only available for quitting smoking in New Zealand, and cytisine is not available in many countries. Typically, treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse.
Objectives The objective of this Cochrane Review was to investigate the comparative benefits, harms, and tolerability of different smoking cessation pharmacotherapies and e‐cigarettes when used to help individuals stop smoking tobacco.
Selection criteria The review included randomized controlled trials (RCTs), cluster‐RCTs, and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment and randomized them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, NRT, and e‐cigarettes) versus control (i.e., no pharmacological intervention, placebo, or another approved pharmacotherapy).
Data collection and analysis Standard Cochrane methods for screening, data extraction, and risk of bias were followed. Primary outcome measures were smoking cessation at six months or longer and the number of individuals reporting serious adverse events (SAEs). The researchers used Bayesian component network meta-analysis, a statistical technique to combine data from the studies into a single analysis, to compare smoking cessation methods, using both direct comparisons within trials and indirect comparisons across trials.
Main results The analysis consisted of 319 RCTs involving 157,179 participants. Of these, 51 were at low risk of bias overall, 104 at high risk, 164 at unclear risk, and 118 reported pharmaceutical or e‐cigarette/tobacco industry funding. However, removing studies at high risk of bias did not change the interpretation of the results.
The analysis found high‐certainty evidence nicotine e‐cigarettes, varenicline, and cytisine were associated with higher quit rates than control. For every 100 individuals, 10 to 19 are likely to quit using an e‐cigarette; 12 to 16 using varenicline; and 10 to 18 using cytisine. Compared to 6 in 100 individuals likely to quit using no medication, e‐cigarette, or placebo. This was closely followed by using two forms of NRT concurrently, such as nicotine patch alongside nicotine gum, lozenges, or nasal sprays. Nicotine patches alone, another NRT alone (e.g., gum, lozenge), and bupropion appeared to help fewer individuals quit but were more effective than control (8, 9, and 9 individuals per 100, respectively). Nortriptyline resulted in the lowest number of individuals quitting smoking; for every 100 individuals using nortriptyline, 6 to 11 are likely to quit.
There was moderate‐certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. The current information for other treatments does not provide clear evidence of SAEs. For all treatments, findings suggest very few individuals experience SAEs. More research is needed on SAEs. However, NRT has been used since the 1980s with no evidence of serious harm.
Conclusions The most effective interventions were nicotine e‐cigarettes, varenicline, and cytisine, all with high certainty evidence, followed by combination NRT. There was also high‐certainty evidence for the effectiveness of nicotine patches, fast‐acting NRT, and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non‐nicotine e‐cigarettes, and tapering of nicotine dose (both low certainty). More research is needed to compare interventions to aid in clinical decision-making.
