Learn more about other treatment options to help patients quit smoking, including varenicline, bupropion and e-cigarettes.
Varenicline (Champix in Canada; Chantix in the US) is a non-nicotine oral treatment that, like NRT, has been shown to be effective in helping smokers quit.28
In phase 2 and 3 studies, varenicline typically tripled the abstinence rates compared with placebo.94 Varenicline is an α4β2 nicotinic acetylcholine receptor (nAchR) partial agonist. It was discovered that α4β2-containing nAchRs play a key role in mediating addiction to nicotine. By binding to these receptors, varenicline causes nicotine-like effects, leading to relief of craving, restlessness and other withdrawal symptoms.28 In addition, the effects of inhaled nicotine are blocked because the target receptors are already bound by varenicline, which attenuates the rewarding and satisfying effects of nicotine from smoking.95
Varenicline comes as 0.5 mg and 1mg tablets that can be prescribed as bulk tablets or as a user friendly format consisting of a 4 week “Starter Pack” and two 4 week “Continuation Packs” (total 165 tablets).
There are 3 quit methods:
There are 2 dosing options:
The patient can continue for the 12-week course or patients who have successfully quit may choose to remain on varenicline for 24 weeks. A 2010 publication by Knight et al. showed a greater 1 year abstinence rate with successfully quit patients who take a further 12 weeks of therapy (27.7%) versus 12 weeks of therapy (22.9%).http://www.sciencedirect.com/science/article/pii/S1098301510603646
There is currently no data for efficacy of a further 12 weeks of treatment in patients who have not successfully quit after 12 weeks of varenicline therapy.
The efficacy of varenicline was demonstrated in five double-blind, placebo-controlled clinical trials (n= 4190). In four 12-week trials, varenicline demonstrated superior efficacy to placebo, as measured by the 4-week continuous quit rate. In these trials, patients were not allowed to use NRT during the drug treatment phase.28
The Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) compared the safety and efficacy of varenicline, bupropion, NRT patch and placebo in over 8,000 patients with and without pre-existing psychiatric disorders from 2011-2015 involving 43 centers and 16 countries. In the EAGLES study, varenicline showed superior efficacy to bupropion, nicotine patch and placebo at the end of treatment (9-12 weeks) (varenicline 33.5%, NRT 23.4%, bupropion 22.6%, placebo 12.5%) and follow-up (9-24 weeks) (varenicline 21.8% bupropion 16.2% NRT 15.7%, placebo 9.4%). This was the largest clinical trial of smoking cessation agents compared head-to-head and was a post marketing double blinded, randomized, triple-dummy, placebo-controlled and active-controlled trial.http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)30272-0.pdf
The use of varenicline in combination with NRT patches shows some differing results. A 2014 study by Koegelenberg et al., the authors concluded that the combination of varenicline and a nicotine patch was more efficacious than varenicline alone in smoking cessation.96 However another 2014 study by Ram et al., involving smokers of >20 cigarettes/day, did not show higher rates of abstinence in varenicline versus varenicline and NRT patch combination at 12 and 24 weeks. In contrast, this same study did show a significantly higher abstinence at 12 and 24 weeks in varenicline and NRT patch in those who smoked >29 cigarettes/day versus varenicline alone.https://www.ncbi.nlm.nih.gov/pubmed/25296623
In 2015, Cheng et al. published a systematic review and meta-analysis on 3 randomized, controlled studies involving 904 patients. Their results showed that both the early and late outcomes were in favour of combination varenicline and NRT patch versus varenicline alone especially if pre-cessation NRT patch is used. Adverse events were similar in both groups except for an increase in skin reactions in the combination group.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508997
Given that varenicline and NRT work on the same receptor, it is unclear how the increased benefit is derived. It is possible that there is not a complete saturation of the nicotinic receptor subtype with varenicline.97
Prescribing considerations – Adverse events/Warnings
In clinical trials with varenicline, the most frequent adverse events were nausea (30%), insomnia (18%), headache (15%) and abnormal dreams (13%). Discontinuation rates due to adverse events in Phase II and III trials were similar to placebo (12 vs. 10%).28
In February 2017, following previous actions from Europe and the FDA, Health Canada removed the Black Box warning of severe neuropsychiatric side effects (depression, mood, agitation, hostility, and suicide related events). This was in light of the results of the EAGLES study. In patients without pre-existing psychiatric illness, varenicline was not found to have an increased incidence of neuropsychiatric side effects compared to placebo (varenicline 1.3%, 2.2% bupropion, 2.5% nicotine patch and 2.4% placebo). In patients with pre-existing psychiatric disorders, there were more reported adverse psychiatric events in each group than in the non pre-existing psychiatric group. However, the neuropsychiatric events reported in the varenicline treated group were no different than placebo (varenicline 6.5%, 6.7% bupropion, 5.2% in nicotine patch and 4.9% in placebo). The labelling for varenicline still lists serious adverse events/warnings such as mood changes, psychosis, hallucinations, paranoia, delusions, homicidal ideation and aggression.
When prescribing patients varenicline, frequent follow-up is recommended when the patient first starts the varenicline, each time the dosage is increased, and then frequently until the patient quits with continued follow-up until the end of the 12 (or 24) week course of therapy.
Learn about NRT options
Bupropion is a non-nicotine oral treatment for smoking cessation originally developed as an antidepressant. Its precise mechanism of action is unknown; however, it is a weak inhibitor of dopamine and noradrenaline uptake and has also been shown to antagonize nAchR function.98 Bupropion can be used alone or in conjunction with NRT. Prior to prescribing bupropion it is recommended that consideration be given to using NRT alone.99
In a double-blind clinical trial, bupropion (50 and 300 mg/day) was shown to be significantly more effective than placebo, as measured by the 4-week abstinence rate. In addition, bupropion (7 weeks at 300 mg/day) was more effective than placebo in helping patients maintain continuous abstinence through 6 months of the study.99
Prescribing considerations – Warnings
There have been clinical trial and post-marketing reports with SSRIs and newer anti-depressants, including bupropion, of severe agitation-type events (e.g., hostility, aggression) coupled with self-harm or harm to others. Rigorous clinical monitoring for suicidal ideation and other behavioural changes is recommended.99
Bupropion should not be prescribed over 300 mg/day due to the risk of seizures.99 The most common adverse events were dry mouth (11%) and insomnia (31%).
Overview and Canadian Perspective
Electronic cigarettes are also referred to E-cigarettes, personal vaporizers (PVs) or electronic nicotine delivery systems (ENDS). An atomizer (battery-powered heating element) heats a liquid (possibly containing nicotine), turning it into an aerosol that can be inhaled and creating a cloud that resembles cigarette smoke.121 The aerosol emitted is not simply water vapour but a high concentration of ultrafine particles.56 A Chinese company, Ruyan, is largely credited with the invention of the E-cigarette, which was released on the Asian market in 2004. “Vaping” (the act of using an E-cigarette) has been considered healthier than smoking because:
Formerly, Health Canada advised Canadians not to buy or use E-cigarettes because the safety of the products (both the nicotine-containing and non-nicotine-containing versions) has not been proven. Under the current regulations, no company has been granted market authorization under the Food and Drugs Act to manufacture and sell E-cigarettes that deliver nicotine.72 Currently E-cigarettes are currently only legal to be used in Canada without nicotine and do not have any current health claims regarding safety or smoking cessation efficacy. Health Canada now plans to regulate E-cigarettes under Bill S-5 (currently going through the House of Commons for approval). These regulations will legalize vaping devices containing nicotine and will regulate these products. Health Canada is currently in the process of creating the regulatory framework for these products, and will deal with areas of federal responsibility such as advertising and promotion, packaging, the product itself and use in federally regulated workplaces and public spaces.
When choosing a smoking cessation method, it is best to consider the clinical evidence of all treatments, as well as what may work for your patients’ needs.
Clinical and safety considerations
For some patients, E-cigarettes may help with harm reduction – reducing the harmful consequences of cigarette smoking, without necessarily reducing or eliminating the use itself.57,58 In Canada, E-cigarettes are not approved to contain nicotine. In other markets, E-cigarettes with nicotine are thought to satisfy the chemical (by replacing nicotine) and behavioral (by mimicking the hand-to-mouth ritual) aspects of cigarette addiction.59 In Canada, the NICORETTE® Inhaler can help address the behavioral aspect, while delivering nicotine which will not be inhaled into the lungs, but absorbed via the oral mucosa. It is authorized for sale by Health Canada.60
There are also several safety concerns to consider with E-cigarettes:
The efficacy of E-cigarettes in smoking cessation has not been well established in randomized, controlled trials. There is some observational evidence of smoking reduction and cessation in E-cigarette users.124,125 However, a meta-analysis of E-cigarette studies for smoking cessation showed that while the majority of studies demonstrate a positive relationship between E-cigarette use and smoking cessation, the evidence remains inconclusive due to the low quality of the research published to date.126
Frequently asked questions
Do E-cigarettes undo some of the de-normalization of smoking?
This is a big potential concern and may be some of the reasons behind them being sold. Many of the E-cigarettes are sold by tobacco companies, which would make one feel that this is their endgame.127 As such, we should be concerned about this, but the evidence for this statement is not yet strong.
It appears that youth try E-cigarettes, but most do not continue them. The Ontario Tobacco Research Unit 2015 RECIG study revealed that:
Are E-cigarettes a gateway to smoking, especially for youth?
In an online study of almost 1200 youths:
So, while some youths trying E-cigarettes are non-smokers, this is by far the minority.128
What are the second-hand and long-term effects of E-vapour?
While there is no true second hand ‘smoke’ from E-cigarettes, it is clear that there are aerosols to which bystanders will be exposed to. However, toxins in the E-cigarette aerosol were shown to be at much lower levels compared with the conventional cigarette emissions.129
Can we count on the chemical composition of E-liquid?
As E-cigarettes are unregulated, there can be great disparity between different products.68,69
In 2009, the FDA conducted an analysis of two brands of E-cigarette cartridges which showed trace levels of carcinogenic nitrosamines in over half of the samples and potentially harmful compounds, such as anabasine, myosmine and β-nicotyrine in most of the tested samples.130 It should be noted that these compounds are also present in tobacco smoke at concentrations that are 100-1000X higher than in E-cigarettes. Propylene glycol, the main ingredient in most E-cigarette cartridges, has been approved for use in food products in Canada131 and is used as a humectant, food preservative, in asthma inhalers and nebulizers, and in theatrical fog machines. Its effects on health are currently controversial.
What is the evidence for efficacy of E-cigarettes?
The evidence for efficacy is unclear and comes from a small number of often poorly done studies. There does seem to be some efficacy in smoking reduction. It should be noted that the studies include those with and without nicotine71 making relevant decisions difficult in Canada, where nicotine-containing E-cigarettes are not legal.
Clearly, there are some people where E-cigarettes can be another “tool in the tool chest” for smoking cessation by dealing with some of the behavioral components of therapy.70 People smoke for a variety of reasons, and as such, need a lot of choices to assist in cessation attempts. Nicotine addiction, habit, stress and lifestyle are all factors that need to be dealt with. Reasons quoted include:132
Legislation is sorely needed in Canada to delineate safe and consistent compounds without nicotine, flavouring or colour to further improve safety. Nicotine can be given in other less dangerous forms to assist in that component of smoking cessation. Attention to the multiple facets of smoking including habit, nicotine addiction and stress relief can help improve smoking cessation success rates.
Get counselling tools
The 2008 U.S. Clinical Practice Guidelines included a review of acupuncture and hypnosis as behavioural/counselling treatments. They concluded that:7
Two types of counselling were recommended:
NEXT: Support Tools >