New research provides clarity on the most effective cessation aids available. Varenicline, cytisine, and e-cigarettes help the greatest proportion of people quit long-term.
Slowly tapering nicotine dose before ending treatment may also boost success rates. Bupropion slightly raises the risk of serious side effects.
Key Facts:
- Varenicline, cytisine, and e-cigarettes have the highest quit rates, helping 8-9 more people per 100 than no treatment.
- Combination NRT works nearly as well, helping 7 more people per 100 quit than no treatment.
- Tapering nicotine dose aids efficacy. Quit rates rise by 1 more person per 100 with tapering.
- Only bupropion clearly raises serious side effect risk, and the increase is small (1 more person affected per 100).
Source: Cochrane Database Syst Rev. (2022)
The Global Tobacco Epidemic
Tobacco use remains highly prevalent worldwide, representing a leading source of preventable death and disease.
Over 20% of all deaths in some high-income nations stem from smoking.
Rates of daily smoking reach nearly 50% of men in multiple low- and middle-income countries as well.
Quitting confers tremendous health gains at any age, largely eliminating excess risk within 10-15 years.
Successfully quitting also brings financial, quality of life, and longevity benefits.
Most smokers want to quit, yet find doing so exceptionally difficult.
Relapse rates exceed 97% in unaided quit attempts lasting less than a year.
Even with counseling alone, long-term abstinence hovers below 30%.
This stubborn reliance on tobacco prompted the emergence of cessation pharmacotherapies.
Beginning with nicotine replacement options in the 1980s, the market expanded to include bupropion and varenicline by 2006.
More recently, e-cigarettes joined the therapeutic arsenal as the first consumer electronic nicotine product.
With choice comes complexity. Clarity is needed regarding the relative effectiveness and safety profiles of the various cessation options now available.
This allows clinicians to channel limited healthcare resources toward the approaches offering smokers the greatest chance of success.
It also guides practice guidelines and healthcare policy aimed at reducing the global burden of tobacco dependence.
Cochrane Review of Smoking Cessation Aids
A systematic review and network meta-analysis published in the Cochrane Database of Systemic Reviews, set out to address this need for clarity.
Researchers conducted extensive literature searches to identify every quality randomized trial ever performed comparing pharmaceutical or e-cigarette interventions against each other or a placebo/control condition on long-term smoking abstinence and side effects.
Searches yielded over 300 eligible studies involving more than 150,000 participants in total.
This made it the largest synthesis of smoking cessation trial data ever completed.
It also represented the first analysis of its kind to include the medication cytisine and e-cigarette options.
The team employed novel statistical techniques allowing indirect comparisons between cessation options not directly pitted against each other.
They also broke down treatments by delivery system and dosing characteristics for more granular findings.
Overview of Findings:
- The top-line conclusions confirmed e-cigarettes and the prescription medications varenicline and cytisine as the most effective options, helping between 8-9 more people per 100 quit long-term relative to no treatment.
- Nicotine replacement therapy (NRT) worked best when combining slow-release patches with faster acting gum or lozenges, with efficacy nearing that of the top performers.
- The researchers also found evidence that tapering NRT dose prior to discontinuation boosts success rates by around 1 quitting subject per 100 compared to abruptly stopping.
- Bupropion was the only intervention with clear links to more frequent serious adverse events like seizures, increasing risk by 1 per 100 users.
- Still, side effects proved rare overall, with absolute rates below 5% even for bupropion. The below sections detail the systematic review’s findings on efficacy, safety, tolerability, and optimal treatment delivery characteristics.
Success Rates of the Various Cessation Aids (Cochrane Review)
Prescription medications
- Varenicline was one of the top performers, helping 12-16 more people per 100 achieve 6-month abstinence relative to placebo. It acts by dampening nicotine’s ability to trigger dopamine release, thereby reducing cravings and withdrawal severity.
- The natural plant alkaloid cytisine functioned similarly to varenicline, assisting 10-18 more quitters per 100 than placebo. It too blocks nicotine from fully activating its brain receptors. Cytisine does not hold approval in many Western countries but costs much less than other pharmaceutical options.
- Bupropion, an antidepressant, aided 9 more people per 100 than placebo, likely via effects on the brain’s reward pathways.
Nicotine replacement therapy (NRT)
- High-dose nicotine patches alone assisted 8-9 more abstainers per 100. Providing sustained background nicotine levels, they prevent severe withdrawal symptoms.
- Other faster-acting NRT modes like gum or lozenges worked just as well alone, promoting 9 more quitters per 100. Their absorption across mouth membranes yields a quicker nicotine rise to help manage sporadic urges.
- Combining the patch with fast-acting gum or lozenges boosted efficacy close to that of varenicline or cytisine. The synergistic approach assists a projected 15 more abstainers per 100 than placebo, making it the most effective singular medical treatment.
E-cigarettes (E-cigs)
- Both nicotine-containing and placebo e-cigarettes increased 6-month quit rates by 8-13 more per 100 compared to counseling alone. Nicotine e-cigs likely function as an NRT. Those without nicotine may aid habit change through continued hand-to-mouth movement.
So in rank order, varenicline, cytisine, nicotine e-cigs, and combination NRT proved most efficacious for smoking cessation by a slight margin over solo NRT patch, solo fast-acting oral NRT, and bupropion.
But all Pharmacological options raised success rates well over placebo or self-help alone.
Even non-nicotine e-cigs showed potential benefits despite very wide confidence intervals around projections.
Side Effects & Safety of Smoking Cessation Treatments
The picture proved more favorable still when gauging serious adverse events (SAEs).
Despite early alarms with varenicline, only bupropion showed compelling links to more frequent SAEs.
And even then, absolute increases over placebo equated to just 1 additional harmful case per 100 bupropion users.
For all other interventions, including varenicline, nicotine patches, gum/lozenges, cytisine, and e-cigs, analyses failed to demonstrate clear differences in SAE rates compared to placebo or counseling only groups.
However, very sparse data limited certainty on non-nicotine e-cigs and the tricyclic antidepressant nortriptyline.
Broadly though, SAEs remained rare, averaging well under 5% across all treatment categories.
Tolerability & Acceptability of Smoking Cessation Aids
Non-serious but troubling treatment side effects can still thwart cessation progress by provoking early dropout.
Combination NRT, bupropion, and varenicline showed the clearest links to more frequent withdrawals relative to control conditions.
But for nicotine patch alone and cytisine, excess dropout rates could not be confirmed, as findings also accommodated no difference from placebo.
Absolute quit attempt failure rates traced primarily to relapse rather than side effect burden for virtually all interventions.
Still, non-nicotine inhalable options like e-cigs may hold an edge in tolerability judging from consumer patterns. Their flexibility and customization better cater to user preferences as well.
Optimizing Nicotine Replacement Therapy: Tapering Works
Beyond easing tolerability, fine-tuning NRT delivery further boosted efficacy.
Among dual-form patch plus oral users, tapering nicotine levels over the last 4 weeks worked better than abruptly going nicotine-free.
The tapered subgroup averaged 1 more abstainer per 100 than those maintaining steady nicotine dosing before quitting.
Gradual weaning may help minimize late-stage relapse triggered by withdrawal discomfort. And oral users can titrate intake as needed when tapering patches.
No other clear delivery distinctions emerged by dosing, treatment duration, or timing of initiation.
Takeaways: Treatments to Stop Smoking (Analyzed)
This rigorous evaluation of the smoking cessation interventions provides clarity.
For individuals seeking maximal odds of quit success with minimal side effect risk, varenicline, cytisine, e-cigs, and combination NRT merit first-line recommendation wherever available.
Yet bupropion and NRT monotherapies still deliver ample benefit to warrant coverage.
Even non-nicotine e-cigs show potential to assist quit attempts through behavioral support.
All things considered, various resource-appropriate options now exist to help the billion-plus cigarette users worldwide shake their lethal addiction once and for all.
References
- Study: Pharmacologic and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses
- Authors: Lindson et al. (2022)
