Tobacco smoking is a chronic disorder based on nicotine dependence and is the single most reversible risk factor of cardiovascular diseases.
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This primer provides an overview of evidence-based smoking cessation interventions, pharmacological and nonpharmacological. Interventions with limited or conflicting data are also discussed. These recommendations are intended for clinicians (physicians and nonphysicians) because smoking cessation services is a fundamental responsibility for health care providers in all settings.Smoking Cessation Framework
A 5-step smoking cessation framework is denoted by the 5 A’s: Ask, Advise, Assess, Assist, and Arrange.
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Step 1 is to ask the patient about the extent of tobacco and nicotine use, including screening for secondhand exposure to smoke. Step 2 consists of advising patients about smoking cessation, because brief assistance of < 5 minutes can increase the success of smoking cessation. Step 3 involves assessing the patient’s willingness to quit, which allows a clinician to understand the smoker’s perspective as well. Step 4 is to offer assistance for those who are motivated to quit, including providing appropriate resources and therapies for patients who smoke at least 10 cigarettes a day. Step 5 is to arrange a follow-up 1-2 weeks after the patient’s anticipated termination date, allowing the clinician to provide encouragement, assess response to therapy, optimize first-line therapies, and monitor for any adverse side effects of pharmacotherapy. Along similar sentiments, the Canadian-based Ottawa Model for Smoking Cessation is another in-hospital smoking cessation framework built on 3 A’s: Ask, Advise, and Act.Pharmacotherapy
Three different classes of drugs are approved in Canada for smoking cessation: nicotine replacement therapy (NRT), bupropion, and varenicline. The efficacy of each drug class is supported by the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) study, a clinical trial that provided head-to-head comparisons of the 3 agents vs placebo in > 8000 smokers.
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Herein, we review the suggested first-line pharmacotherapies for smoking cessation. The different agents available and their pharmacological profiles are included in Table 1.Table 1First-line medications used for smoking cessation in adults
| Drug | Dosing | Administration | Advantages | Disadvantages | Major adverse effects |
|---|---|---|---|---|---|
| Nicotine patch |
|
|
| User cannot increase nicotine level in case of craving | Skin irritation, insomnia, vivid dreams |
| Nicotine gum |
|
|
|
| Mouth irritation, jaw soreness, heartburn, hiccups, or nausea |
| Nicotine lozenge |
|
|
| Unpleasant taste | Mouth irritation, hiccups, heartburn, or nausea |
| Bupropion | 150 mg pill |
|
|
| Insomnia, agitation, dry mouth, headache |
| Varenicline | 0.5 mg pill to start, then titrate up to 1 mg pill |
|
|
| Nausea, insomnia, vivid dreams |
NRT
NRTs provide temporary replacement of nicotine from cigarettes and are available as long-acting transdermal patches or short-acting agents such as gum and sublingual tablets/lozenges. Short-acting preparations often require frequent use throughout the day and lead to more fluctuating blood nicotine levels. They are often combined with a nicotine patch to better control cravings and withdrawal symptoms.
Transdermal patch
The transdermal patch provides a slow and continuous release of nicotine over 24 hours and is available in 7 mg, 14 mg, and 21 mg regimens. Each cigarette contains approximately 1-2 mg of nicotine. In Canada, 1 pack contains 25 cigarettes. Therefore, a 1-pack per day smoker is receiving approximately 25 to 50 mg of nicotine every day. Compared with cigarettes, which produces spikes in blood nicotine levels when used, the patch produces more consistent blood nicotine levels. However, cravings might still persist when using the patch if nicotine levels fall below the peaks produced during cigarette use. Major side effects include localized skin irritation, insomnia, and vivid dreams.
Nicotine gum
In Canada, Nicotine gum is available as 2 mg and 4 mg preparations. Chewing the gum releases nicotine, which is absorbed through the oral mucosa. A proper method of chewing, referred to as “chew and park” is paramount for optimal results. Dosing is determined by how soon the first cigarette is typically smoked upon awakening, with users possibly using up to 25 pieces of gum per day. The dosage absorbed in the body is also typically only half of the prescribed amount. Common side effects include mouth irritation, jaw soreness, heartburn, and hiccups. Overly vigorous chewing can exacerbate temporomandibular disorders in denture wearers.
Nicotine lozenge
The available formulations include 1 mg and 2 mg strength with pharmacokinetics, dosing regimens, and side effects profile similar to that for the nicotine gum. The maximum daily limit is 16 pieces. The major advantage of the lozenge over the gum is that it can be used in patients with temporomandibular disorders and dentures.
Bupropion
Bupropion is an antidepressant that inhibits the neuronal uptake of norepinephrine, serotonin, and dopamine. Bupropion is prescribed as 150 mg once daily for 3 days, then 150 mg twice daily for 12 weeks. Compared with placebo, bupropion increases the success of smoking cessation (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.60-2.06).
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Head-to-head comparisons of bupropion with NRT showed similar efficacy. Bupropion use is contraindicated in patients with a history of seizure disorder or recent major head trauma.4
The risk of seizure with bupropion use is dose-dependent and is most often described in the setting of overdose and/or in patients with other risk factors for seizures. One of the major side effects of bupropion is insomnia.4
Clinicians should routinely screen patients for changes in sleep behaviour and if insomnia is present, the evening dose can be discontinued.Varenicline
Varenicline is a nicotine receptor partial agonist. Varenicline has been shown to be the most effective smoking cessation agent available, because it reduces withdrawal symptoms by preventing attachment of nicotine-to-nicotine receptors. The prescribing dose is 0.5 mg once daily for 3 days, then 0.5 mg twice daily for 4 days, followed by 1 mg twice daily for 12 weeks. Varenicline has been shown to increase the odds of quitting compared with placebo (OR, 2.96; 95% CI, 2.12 to 4.12 for 4 trials), indicating it superior to NRT vs placebo (OR 1.71, 95% CI, 1.55 to 1.88 70 trials), and Bupropion vs placebo (OR 1.56, 95% CI, 1.10-2.21 for 12 trials).
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Common side effects include nausea and insomnia. Similar to bupropion, there were early concerns of neuropsychiatric and cardiovascular side effects with varenicline, which were not supported by subsequent studies including the EAGLES trial.Electronic cigarettes
Electronic cigarettes are emerging as a potential aid in smoking cessation, albeit with mixed evidence. Electronic cigarettes (ECs) are handheld devices that use a battery source to aerosolize a liquid. Many EC products vary in the rate and amount of nicotine delivery and are currently being evaluated as another method for smoking cessation. A Cochrane meta-analysis consisting of 61 completed studies, representing 16,759 participants, reported moderately good evidence that nicotine ECs increase smoking cessation rates compared with non-nicotine ECs (risk ratio [RR], 1.9; 95% CI, 1.21-3.13), and NRTs (RR, 1.5; 95% CI, 1.21-1.93).
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However, using ECs for cessation might not improve successful smoking cessation or prevent relapse as well in the real world compared with in clinical trials. A 2021 US meta-analysis conducted on 55 observational studies and 9 randomized clinical trials reported that ECs were not associated with increased smoking cessation rates in the real-world adult population. Interestingly, the same study reported that there was a high cessation rate reported by EC users than conventional pharmacotherapy users in randomized clinical trials (RR, 1.56; 95% CI, 1.17-2.06), indicating a possibility that ECs are a useful cessation aid when clinician-mediated follow-up is present.
Although EC use is less harmful than cigarettes, prolonged EC use might be a risk factor in cardiovascular disease, including neurohumoral activation, oxidative stress, inflammation, endothelial function, and thrombosis. There is also limited data on the use of ECs on vaping cessation and exacerbating vaping dependency. Thus, more data are needed regarding its effectiveness in smoking cessation before an assessment of its use can be made regarding smoking cessation. Presently, ECs have not been approved for smoking cessation nor has any application been made by EC manufacturers to approve these devices for smoking cessation.
Nonpharmacological Interventions
Cytisine (labelled as a natural health product)
Recent attention has been given to cytisine, a naturally occurring plant alkaloid, as a highly effective smoking cessation agent. Like varenicline, it is a partial agonist that selectively binds to the α4β2 nicotinic acetylcholine receptor subtype, which mediates nicotine dependence in the body. Cytisine has been sold in Eastern Europe as an inexpensive smoking cessation aid for the past 50 years, although it is currently unavailable elsewhere. A 2014 pragmatic, noninferiority trial in New Zealand with 1310 adult daily smokers that compared cytisine use with NRT for 8 weeks revealed that cytisine was superior to NRT in smoking cessation (9.3% improvement; 95% CI, 4.2-14.5), but it was associated with higher self-reported adverse effects. The side effects of nausea, vomiting, and sleep disorders were also reported in other studies.
Behavioural therapy
A variety of behavioural therapy interventions to aid in smoking cessation are available, with tailored programs provided through specialty clinics or smoking cessation programs. A 2017 systematic review of 49 trials (approximately 19,000 participants) revealed that individual behavioural therapy for smoking cessation was more effective than a minimal contact control arm (of brief advice, standard of care, or provision of self-help materials) when pharmacotherapy was not offered to any participants (RR, 1.57; 95% CI, 1.40-1.77; I2 = 50%).
It is noted that for some patients, brief clinician counselling in the office is the only viable option for face-to-face care. This option can be supplemented by external resources, such as telephone quit-line support and counselling. A 2013 systematic review and meta-analysis of various smoking cessation methods revealed that telephone counselling helped increase cessation rates when not initiated by helplines (51 studies; 30,000 participants; RR, 1.27; 95% CI, 1.20-1.36). Acupuncture, hypnotherapy, and alternative medicine might commonly be sought out by patients, however, evidence is lacking on their efficacy to improve cessation rates compared with placebo and is thus not recommended for smoking cessation. Overall, combination therapy of pharmacotherapy plus behavioural therapy with regular follow-ups and prolonged use should be the preferable approach to smoking cessation.
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An expanded overview on smoking cessation with complete citations are provided in the Supplementary Material.
Conclusion
This primer provides an overview of evidence-based smoking cessation interventions following the 5 A’s framework: ask, advise, assess, assist, and arrange. All patients should be screened for smoking status regardless of clinical setting, because clinicians should be experienced in routinely prescribing evidence-based smoking cessation therapies. For hospitalized patients, smoking cessation interventions should be started in-hospital. Clinicians should be familiar with the various smoking cessation therapies available, including pharmacotherapies (NRT, bupropion, varenicline), ECs, cytisine, and behavioural therapy. On the basis of the available evidence, we suggest varenicline as the first-line therapy for smoking cessation, with combination therapy when possible.
Funding Sources
The authors have no funding sources to declare.
Disclosures
The authors have no conflicts of interest to disclose.
Supplementary Material
- Supplementary Material
References
- Treatment of tobacco smoking: a review.JAMA. 2022; 327: 566-577
- Smoking cessation: an update.Indian J Chest Dis Allied Sci. 2014; 56: 161-169
- Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial.Lancet. 2016; 387: 2507-2520
- Pharmacological interventions for smoking cessation: an overview and network meta-analysis.Cochrane Database Syst Rev. 2013; 5: CD009329
- Electronic cigarettes for smoking cessation.Cochrane Database Syst Rev. 2021; 9: CD010216
Article Info
Publication History
Published online: May 08, 2022
Accepted:
May 2,
2022
Received:
February 23,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 The Authors. Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society.
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