Treating tobacco dependency

Alternative treatments

There is considerable evidence for the effectiveness of varenicline and bupropion. However, there are other treatments available which are used in some countries. These include cytisine and nortriptyline.

Cytisine

Cytisine is an alkaloid originating from some plants belonging to the Leguminosae (Fabaceae) family and like varenicline, cytisine is a partial agonist at α4ß2 nicotinic acetylcholine receptors²⁴. Cytisine has been used to treat tobacco dependence in some eastern/central European and central Asian countries for more than 50 years²⁴ and is a low cost option²⁵. Cytisine is currently licensed in four EU countries (Bulgaria, Poland, Latvia, Lithuania) and 13 non-EU countries (Azerbaijan, Armenia, Belarus, Georgia, Kazakhstan, Kyrgyzstan, Moldova, Russia, Serbia, Tajikistan, Turkmenistan, Uzbekistan, Ukraine)²⁶.

A single centre placebo-controlled study of 740 patients in Poland showed that after 12 months, continued abstinence from smoking was 8.4% in the cytisine group vs 2.4% in the placebo group (P=0.001)²⁷. A meta-analysis including eight studies confirmed that cytisine is an effective medication for tobacco dependence, increasing the likelihood of successful treatment by 75% compared to placebo²⁴.

It is difficult to compare cytisine with other tobacco dependence medications because only data from one pragmatic randomised clinical trial is available. This study was an open-label, non-inferiority trial of cytisine vs. NRT in New Zealand (N = 1,310). At all timepoints studied cytisine was more effective than NRT. Quit rates at six months were (22% for cytisine vs 15% for NRT, P=0.002)²⁶. Studies are ongoing to compare its effects with varenicline²⁴.

Dosage

Cytisine is taken orally over 25 days, starting from one 1.5 mg tablet or capsule every 2 hours tapering to two tablets per day²⁴.

Possible side-effects

Aggregated gastrointestinal disorders comprising stomach ache, dry mouth, dyspepsia, and nausea, were reported more frequently in participants receiving cytisine than in those receiving placebo²⁴.

Nortriptyline

Nortriptyline has been shown to be effective for tobacco dependency but is not licensed for this use. It is a low-cost drug so can be considered if cost is a limiting factor²⁵. Nortriptyline has moderate-quality evidence of increased quit rates (six trials, 975 participants)²¹. Compared to placebo controls there is a significant benefit of nortriptyline over placebo (N = 975, relative risk 2.03, 95% CI 1.48-2.78)²¹. In pooled analysis when compared to bupropion however, whilst not significant, a clinically useful difference in favour of bupropion is not excluded (N = 417, relative risk 1.30, 95% CI 0.93-1.82) ²¹.

Dosage

Nortripyline treatment should be started 10 to 28 days before a set quit date. The initial dose is 25 mg daily, which is increased gradually to 75–100 mg daily over ten days to five weeks. The maximum dose can be continued for eight to 12 weeks and tapered down at the end to avoid withdrawal symptoms that may occur if it is stopped abruptly²⁹.

Side effects

These include sedation, dry mouth, light-headedness and the risk of cardiac arrhythmia in patients with coronary heart disease limits its application²⁵.

Effective evidence-based interventions

A combination of pharmacotherapy and support has been shown to be the most effective strategy to successfully stop smoking¹. In the UK for example, interventions are ranked on the strength of evidence (Table 1).

Table 1. Evidence and usability of stop smoking interventions (adapted from NICE³⁰).

Let’s now take a look at these interventions listed in order of their strength of evidence.

Behavioural support

Behavioural support ranges from patient leaflets and helpline/app support through to multisession group therapy programmes or repeated individual counselling. A systematic review and meta-analysis has shown that internet-based programs incorporating behaviour change techniques are associated with increased smoking cessation in the general population³¹. The availability of behavioural support will vary by country and region.

There is good evidence of benefit for individually tailored self-help materials or more intensive advice or counselling¹.

Individual support

Individual behavioural support involves scheduled face-to-face meetings between a smoker and a counsellor trained in smoking cessation. In the UK, this typically involves weekly sessions over a period of at least 4 weeks after the quit date and is normally combined with pharmacotherapy⁵. In Norway individual support consists of a minimum of four consultations, the first before the quit date, the second within five days after the quit date, the third after one to three weeks and the fourth three months after quitting⁹.

Want to know what exactly what should be discussed in each of these meetings? Take a look at the NCSCT standard treatment programme (link will take you to an external site) which details the content of each successive consultation.

Short of time? In a routine consultation when time is more limited maybe include a medication discussion and some brief advice along with praise and encouragement.

There have been a number of analyses which have evaluated the effectiveness of behavioural interventions for tobacco dependence. In terms of individual face-to-face counselling, counselling alone showed significant benefit (27 trials, risk ratio [RR] 1.57 [95%CI 1.40 – 1.77]) when compared with minimal contact control⁵. Interestingly, comparing less intensive counselling interventions (which still involved more than 10 minutes face-to-face contact) showed no evidence of benefit compared with more intensive counselling (4 trials RR 1.42 [95%CI 0.98 – 2.06])⁵.

Group support

Group behavioural support (if available) involves scheduled meetings in which smokers receive information, advice and encouragement and some form of behavioural intervention (for example, cognitive behavioural therapy). In the UK this therapy is usually offered weekly for at least the first four weeks of a quit attempt and normally combined with pharmacotherapy⁵. In Spain there are different types of group support with patients usually receiving between five and ten sessions.

A review of the effectiveness of group-based behavioural interventions found them to be more effective than no intervention (9 trials RR 2.60 [95%CI 1.80 – 3.76]) or self-help (13 trials, RR 1.88 (95%CI 1.52 – 2.33]) or brief advice (16 trials RR 1.25 [95% CI 1.07 – 1.46]). There was no evidence that group style interventions were any more or less effective than intensive individual counselling⁵.

E-cigarettes

E-cigarettes (‘vaping’) are an alternative nicotine delivery system for tobacco smokers. E-cigarettes are increasingly being used globally and form part of stop smoking or harm reduction programmes in some countries². A randomised controlled trial has shown that they are more effective than NRT in programmes that include behavioural support³².

Previous trials have suggested that e-cigarettes are effective as an aid to stop smoking and that at least in the short-term also safe and tolerable. The most recent trial in 886 patients in the UK supports this finding and shows that e-cigarettes are around twice as effective as NRT (1-year abstinence rate 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group [relative risk, 1.83; 95% CI, 1.30 to 2.58; P<0.001])³².

With further head-to-head trials and long-term data on the lung safety of e-cigarettes required, the Primary Care Respiratory Society (PCRS) recommend that patients be offered the most effective and least harmful methods to support a quit attempt including very brief advice, behavioural support, (NRT) and pharmacotherapy (bupropion, varenicline)³³.

Special populations

There are a number of circumstances in which treatment for tobacco dependence is especially warranted. While there are obvious situations of chronic disease that suggest action (respiratory disease, cardiovascular disease, cancers), there are also other chronic diseases more prevalent in smokers to consider (HIV, tuberculosis, and patients living with mental health conditions). Other factors to consider include pregnancy and breastfeeding, children and adolescents and sociocultural background and socioeconomic status²⁵.

Pregnancy and breastfeeding

Treating tobacco dependence is particularly important during pregnancy as smoking in pregnancy remains one of the few preventable factors associated with pregnancy complications, stillbirth, preterm birth, low birthweight and long-term health implications such as asthma²⁵.

NRT is safer than tobacco and HCPs are advised to offer this option to all pregnant women who need help to quit smoking. Shorter-acting forms are preferred, such as a 16 hour patch plus oral NRT². For breastfeeding mothers the use of nicotine gum, lozenges, or nasal spray immediately after a breastfeed is recommended so that blood levels of nicotine have fallen before the next feed².

Please note that there are NRT restrictions in pregnant and breast feeding women in some countries. Follow the link to the IPCRG website which contains links to national guidelines.

If pregnant women are successful and stop smoking, post-partum follow-up is important to reduce relapse rates²⁵.

Children and adolescents

The European Union under the auspices of the World Health Organization Framework for Smoking banned the sale of flavoured tobacco products, which are known to be attractive and to seem more innocuous to young people and non-smokers³⁴.

About 80% of smokers begin smoking during their teenage years, with nicotine dependency developing very rapidly in teenagers²⁵. For this reason, HCPs need to integrate tobacco counselling into the health assessments of teenagers. Encouragingly, adolescents aged 16–17 years were the age group most likely to report trying to quit smoking in the previous 12 months, according to an annual survey by ASH. However, ASH also reported that the proportion of 16–17-year-olds doing so declined from 53% in 2007 to 35% in 2019³⁵.

A Cuban study of nearly 150,000 adults found that one-third of participants who smoked regularly at recruitment began smoking in childhood. The risk of premature adult mortality was approximately doubled in adults who started to smoke in childhood. Starting before the age 10 was associated with nearly 3 times the excess risk as starting at age 15 or older. Smoking cessation was uncommon in this population, but participants who quit smoking before the age of about 40 avoided most of the excess risk associated with prolonged smoking. A re-examination of US data relating adult mortality to starting to smoke regularly before the age of 15 years revealed similar patterns³⁶.

Sociocultural background and socioeconomic status

In Europe, stop smoking rates have been higher and smoking uptake lower in the past 10 years among groups with higher socioeconomic and education status²⁵. Independent of the desire to quit, patients who are socioeconomically deprived face additional challenges and may need more support to stop smoking and avoid relapse. These groups stand to benefit most from well-directed support from their primary HCPs²⁵. In the latest Tobacco Control Plan for England (2017–2022), the Department of Health writes that smoking and its associated harms are greatest among the poorest and most vulnerable, with the difference in life expectancy being as much as 9 years between the poorest and richest. About half this difference is due to smoking. Not only are smokers more likely to die earlier than non-smokers, but they are also more likely to suffer many years in poor health and are less likely to be in work³⁷.

Mental health conditions

Smoking rates are substantially higher in patients with psychiatric disorders than in the general population with depression being strongly related to smoking²⁵, while one-third of all cigarettes are smoked by people with a mental health disorder³⁸.

The effect of stopping smoking on anxiety and depression are equal or larger than those of antidepressant treatment for mood and anxiety disorders².

The prevalence of smoking is 41% in people with a severe mental illness (schizophrenia or bipolar disorder) registered with a GP compared with an all-time low prevalence of 15% in the general population. The life expectancy of patients with a severe mental illness is up to 20 years less than in the general population (closer to the general populations in the 1950s). Despite coordinated efforts within health and other services, particularly since 2008, the differences in life expectancy between people with severe mental ill health (SMI) and the rest of the population has increased. The largest preventable component of premature death for this group is smoking³⁹.

Smokers with severe mental illness smoke cigarettes intensively and extract more nicotine from each cigarette becoming more nicotine-dependent⁴⁰. Given that patients with severe mental illness die on average 20–25 years earlier⁴⁰ mainly due to an increase in smoking-related-diseases (heart disease, cancer, cerebrovascular, respiratory and other lung diseases), treating tobacco dependence should be considered essential for patients with mental illness²⁵. However, HCPs are reluctant to tackle smoking in these patients for fear of worsening a patients’ mental health, but actually stopping smoking improves mental health and offers multiple health benefits as it does for every smoker.

The Smoking Cessation Intervention for Severe Mental Illness (SCIMITAR+) trial in heavy smokers with bipolar disorder or schizophrenia showed that a combined behavioural and pharmacological smoking cessation intervention designed for use with mental health challenges, but additionally adapted for severe mental illness, was more effective than usual care⁴⁰.

The intervention consisted of behavioural support from a mental health smoking cessation practitioner, together with pharmacological aids for smoking cessation, which had been adapted for people with severe mental illness to include extended pre-quit sessions, cut down to quit, and home visits. Usual care was access to local smoking cessation services not specifically designed for people with severe mental illnesses)⁴⁰. The proportion of smokers who quit at 6 months was significantly higher in the intervention group than in the usual care group: 14% (32/217) versus 6% (14/217), respectively (risk difference 7·7%, 95% CI 2·1–13·3; OR 2·4, 95% CI 1·2–4·6; P = 0·010). The proportion of smokers who had quit at 12 months was higher in the intervention group than in the usual care group, but not significantly so suggesting that more effort may be needed for sustained quitting in people with severe mental illness⁴⁰.

Psychiatrists meet the highest proportion of tobacco-dependent patients of any speciality⁴¹.

In 2018, the Royal College of Psychiatrists recommended that psychiatrists consider prescribing varenicline when clinically indicated as one of the options for patients with severe mental illness to stop smoking. Concerns have been expressed about adverse neuropsychiatric events with varenicline, but short-term varenicline is effective and safe over its 12–week course. Evidence for its safety included a cohort study of 80,660 men and women (18–95 years) that found no clear evidence for the association of varenicline with self-harm, increased depression, or suicidal ideation. In addition, a double-blind, randomised, placebo-controlled clinical trial concluded that there was no significant increase in neuropsychiatric adverse events in patients prescribed varenicline⁴¹.

E-cigarettes (vaping) have become the most popular device used in self-directed attempts to stop smoking. It is likely that many patients with a severe mental illness, who are smokers, are using, have used, or have considered using, electronic cigarettes as a way to quit smoking. It is therefore important that psychiatrists can provide reliable advice on the benefits and risks of their use.

Stopping smoking has also been shown to have benefits for individuals with anxiety or depression. One study found that the effects of stopping smoking were equal to, or larger than, those of antidepressant and antianxiety treatments on mood and anxiety disorders².

Want to know how to deliver effective Very Brief Advice? Explore our patient case studies for guidance.

Impact and burden of tobacco dependence

Worldwide, tobacco use causes more than 8 million deaths per year, with more than 7 million due to direct tobacco use and about 1.2 million due to passive second-hand smoking⁴². On average, smokers die 10 years earlier than non-smokers⁴³. Tobacco smoking is a huge burden, both for patients themselves and for society, and it has been linked to an increased risk of COVID-19 and severity of the outcome.

Patient burden

Smoking harms nearly every organ of the body⁴⁴ yet many people continue to smoke. This may be for a number of reasons:

• Smoking is addictive and not easy to stop. Among smokers who are aware of the dangers of tobacco, most want to quit. Counselling and medication can more than double a tobacco user's chance of successful quitting⁴⁵.
• Smokers not accurately perceiving the extent to which smoking increases adverse health outcomes. For example, in a study which examined perception of risk of lung cancer in the US, smokers considerably underestimated the relative risk of smoking and so underestimated the importance of smoking cessation to them as an individual⁴⁶.
• Smokers not aware of the full extent of smoking-related health risks. Indeed, the 2015 Global Adult Tobacco Survey (GATS) in China revealed that only 26.6% of Chinese adults believe smoking causes lung cancer, heart disease and stroke⁴⁵.

Health consequences causally linked to smoking

Click on the link below to view interactive infographics that detail all the health consequences causally linked to smoking^44,47,48. You can use these with your patients to highlight some aspects important to them or which you suspect they are unaware of.

Launch 'Health consequences linked to smoking' interactive infographic

The evidence is sufficient to infer that cigarette smoke compromises immune homeostasis and that altered immunity is associated with an increased risk for several disorders⁴⁴.

Smoking and the novel coronavirus disease 2019 (COVID-19)

Coronavirus disease 2019 (COVID-19) is caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), initially thought to primarily affect the respiratory system with the classic trial of symptoms, fever, cough and dyspnoea⁴⁹. In more severe and critical cases, infection can lead to acute respiratory distress syndrome (ARDS) related to severe viral pneumonia, progression on to mechanical ventilation and death⁴⁹.

During the COVID-19 pandemic, the issue of tobacco smoking became important as a risk factor for increasing transmission of COVID-19. The WHO Framework Convention on Tobacco Control warned against COVID-19 transmission via tobacco smoking, for example, through sharing waterpipes or other smoking products, spitting out chewed tobacco, or being more likely to touch the face or mouth during smoking⁵⁰. Fifteen countries in the WHO’s East Mediterranean Region temporarily banned the indoor and outdoor public use of water pipes, potentially opening the door further to future tobacco control in the region^34,51.

COVID-19 fatalities are higher among people with pre-existing conditions for which tobacco is a main risk factor⁵².

It became clear that COVID-19 fatalities were higher among people with pre-existing conditions, including several non-communicable diseases for which tobacco is a main risk factor, such as cardiovascular disease, chronic pulmonary obstructive disorder (COPD), and diabetes⁵². In addition, prior to COVID-19, smoking was known to adversely affect different organ systems, including the immune system and respiratory tract, and to impact on smokers’ predisposition to, or outcome of, respiratory diseases^53,54. Impaired immunity due to smoking has been estimated to double the risk of tuberculosis and to increase the risk of pneumococcal, legionella and Mycoplasma pneumoniae by several-fold⁵⁵. Smokers are at increased risk of contracting influenza and have a worst prognosis compared to non-smokers⁵³. There was an expectation that tobacco smoking might similarly impact infection with SARS-CoV-2⁵².

Click here for more information on tobacco cessation during the COVID-19 pandemic and the role of HCPs in reducing smoking dependency.

Health consequences causally linked to second-hand smoke

Exposure to second-hand tobacco smoke has been causally linked to cancer, respiratory, and cardiovascular diseases, and adversely affects infants and children.

In adults, second-hand smoke has been linked to stroke (20-30% increased risk), lung cancer, coronary heart disease, chronic respiratory symptoms and acute respiratory illnesses, influenza, pneumonia, infections, and nasal irritation⁵⁶.

In children, second-hand smoke is associated with persistent adverse effects on lung function, middle ear disease, sudden infant death syndrome and a small reduction in birth weight⁵⁶.

Health consequences suggested to be linked to smoking

There are also many conditions where evidence for a link with smoking is suggestive rather than sufficient. These include breast cancer, idiopathic pulmonary fibrosis (IPF), asthma, spontaneous abortion and some birth defects, dental caries and Crohn’s disease⁵⁶.

It is important to explore your patients’ beliefs about the dangers of smoking and they may be more receptive to learning how stopping smoking will benefit them in a number of other ways.

Communicate the individual benefits to health

The sooner patients stop smoking the more they can reduce their chances of getting cancer or developing heart disease. Indeed, stopping smoking before age 40 reduces the risk of dying from smoking-related disease by about ~90% and stopping before 30 returns life expectancy to normal⁵⁷ (Smokefree.gov).  Research shows that quitting smoking promotes replenishment of the bronchial epithelium from quiescent cells that have avoided tobacco mutagenesis⁵⁸. Figure 2 provides short- and long-term benefits which may help motivate patients to try and quit.

Figure 2. Timeline of potential short- and long-term benefits of stopping smoking (adapted from cancer.org⁵⁹).

Communicate the financial benefits of stopping smoking

Smokers have higher life insurance premiums and other ancillary expenses, such as dental hygiene, increased cleaning costs (home, car and clothing) and lower resale values of property⁶⁰. Of course, patients will start saving money as soon as they stop smoking. Smoking is generally an expensive habit although the price of a packet of cigarettes varies considerably between different countries (Figure 3). A pack-a-day habit based on 2019 prices in Canada (mid-table) equates to a monthly cost of €284, an annual cost of €3,406 and over 10 years €34,055.

Figure 3. The price of a pack of cigarettes around the world (adapted from Statista.com⁶¹).

A pack-a-day habit based on prices in Canada (mid-table) equates to a monthly cost of €284, an annual cost of €3,406 and over 10 years €34,055.

Given that smoking is significantly associated with lower income worldwide⁶², highlighting the potential cost savings to patients in their country could be an added incentive to encourage quitting and should resonate with teenagers, along with the benefits on their appearance and wellbeing²⁵.

Communicate the benefits to personal appearance and wellbeing

Maybe add your own examples of things that might appeal to your patients. Factors to consider include⁶³:

• food tastes better (as the chef intended)
• sense of smell returns to normal (fully appreciate the smell of freshly-cut grass)
• better smelling breath, hair, and clothes (a new fresh non-smoking wardrobe bought with the cost savings)
• teeth and fingernails stop yellowing (smile more)
• ordinary activities do not cause breathlessness (improved circulation means improved fitness for climbing stairs or housework)
• reduction in the damaging effects of tobacco on appearance, including premature wrinkling of skin, gum disease and tooth loss (more youthful appearance).

Socioeconomic burden

The cost of smoking extends far beyond the price of a packet of cigarettes. A recent analysis of the economic cost of smoking-attributable diseases in countries throughout the world (including low- and middle-income settings) estimated the healthcare expenditure to be 5.7% of global health expenditure (purchasing power parity [PPP] $467 billion, [US$422 billion]) in 2012 (Figure 4)⁶⁴.

Figure 4. The economic cost of smoking-attributable diseases in PPP international dollars (adapted from Goodchild et al⁶⁴).
PPP, purchasing power parity; SAHE, Smoking-attributable health expenditure.

Combining health expenditure and productivity loss increased the smoking bill to 1.8% of the world’s annual gross domestic product (PPP, $1,852 billion or US$1,436 billion)⁶⁴.

Want to know how to deliver effective Very Brief Advice? Explore our patient case studies for guidance.

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