Overview

Smoking is a chronic issue throughout the United Kingdom (UK). In 2022, 12.7% of the adult population in England were smokers, with Scotland having 15% in the same year. There is a greater degree of smoking in males than females in both areas, with the more deprived areas being largely affected. Although smoking is an ongoing problem, there is a continual downtrend in the number of smokers over the years. This may be due to an increase in accessibility to smoking cessation services available.^1,2

Smoking cessation programmes are widely available in England and Scotland. These programmes are available in general practitioner (GP) practices, hospitals, prisons and in pharmacies.³ In England from April to December 2024, 162,655 patients used these services to stop smoking, and of these individuals, 53.8% successfully quit.⁴ In Scotland in September 2024, the NHS board was able to achieve 37% towards its annual local delivery plan standard, where 2,616 patients were able to quit towards the target of 7,026.⁵ Currently, there are numerous treatments available to aid in quitting. For both NHS England and Scotland, nicotine replacement therapy (NRT) is available in different formulations such as patches, lozenges, gums, sublingual tablets (dissolves under the tongue), nasal sprays and an inhalator. In addition, medicines such as varenicline (Chantix®) and bupropion (Zyban®) are also available to stop smoking. Of these options, one medicine can be combined with one or more types of NRT. Moreover, patients can also be on more than one NRT for additional support (for example, on patches and taking lozenges at the same time).⁶

Complications caused by smoking

Smokers, especially those smoking long-term, are at a higher risk of developing detrimental health complications and adverse effects. Examples include:⁷

• Higher degree of inflammation
• Dampened immune response
• Higher cholesterol levels
• Increased risk of developing lung diseases (chronic obstructive pulmonary disease (COPD), pneumonia, lung cancer and possible tuberculosis)
• Type 2 diabetes
• Worsened asthma
• Gum disease
• Heart diseases (stroke, abdominal aortic aneurysm)
• Reduced eye health (cataracts)
• Rheumatoid arthritis
• Reduced bone health (hip fractures)
• Increased risk of mortality
• Potentially reduce fertility

Complications caused by nicotine withdrawal

It is generally not recommended for patients to stop smoking suddenly (“go cold turkey”) as it can come with unwanted effects from nicotine withdrawal. This can result in patients finding it more challenging to quit. Withdrawal symptoms can occur between four to twenty-four hours after stopping, especially in chronic smokers. The most common adverse effects include: increased irritability, anxiety, low mood, finding it hard to concentrate, raised appetite, insomnia and feeling restless. Other symptoms that can occur, but are less common, are constipation, feeling nauseous, dizzy and having nightmares.⁸

Treatment options

Nicotine

NRT is considered a first-line option in stopping smoking; it provides the addictive component of nicotine without the harmful substances in cigarettes. Patches are available in 16 and 24-hour preparations and provide a slow release of nicotine into the bloodstream, where peak levels are reached between 8 to 10 hours. The patches are usually used in conjunction with other NRT preparations as they provide a faster onset of action and help with strong, immediate cravings. This includes: gums which provide nicotine quickly with peak levels after 20 to 30 minutes, lozenges, a nasal spray that provides nicotine within 10 to 15 minutes, an oral spray that provides nicotine within 13 minutes and the inhalator that not only supplies nicotine but provides the hand-to-mouth sensation that is missing when attempting to stop smoking. NRT are provided free of charge in both English and Scottish community pharmacies upon registering for the smoking cessation service, and the programme lasts for twelve weeks.⁹

Mechanism of action

Nicotine stimulates the nicotinic acetylcholine receptors (NAChRs) in the brain, which release dopamine and other various neurotransmitters. Dopamine release triggers the brain’s reward system, causing pleasure. This pleasure is similar to cigarette smoking, which minimises the withdrawal symptoms.¹⁰

Side effects

The most common side effects with NRT include nausea and vomiting, headaches, dizziness, heart palpitations, excessive sweating and skin reactions like rashes or hives. For oral formulations (gums, sublingual tablets, lozenges, oral spray, inhalator), it can cause a dry mouth and irritate the mouth and throat. The nasal spray can cause nose bleeds, sneezing and may irritate the nose. In addition, patches can cause sleep disturbances by producing vivid dreams that can lead to insomnia.⁹

Varenicline

Varenicline (Chantix®) is an oral tablet that is available in 0.5 mg and 1 mg strengths. This is a prescription-only medicine that can be prescribed by a healthcare provider. This medicine can also be provided in community pharmacies in Scotland free of charge through a patient group direction initiative by having a consultation with a pharmacist. Pharmacies in England can also supply this initiative; however, charges may be applied.

When starting varenicline, the patient is on an initiation dose, which is usually started one to two weeks before the target quit date. The patient takes 0.5 mg once daily for three days, which is then increased to 0.5 mg twice a day for four days. After initiation, they are then moved on to the maintenance dose of 1 mg twice a day for eleven weeks, which aligns with the twelve-week smoking cessation programme. This course can be continued after twelve weeks to prevent potential relapses in those who have quit smoking.¹¹

Mechanism of action

Varenicline is a partial NAChR agonist that strongly binds to the α4β2 subtype, which triggers the release of dopamine and activates the brain’s reward system. Varenicline has also been shown to bind to α6β2* subtypes, and these are also involved in nicotine dependence. As varenicline is a partial receptor agonist, it means that there is a lower risk of abuse potential compared to nicotine, which is present in cigarettes and NRT. The drug also has antagonist properties by competing with nicotine and binding more strongly to the receptors to reduce nicotine dependence and withdrawal symptoms.¹²

Side effects

The most common side effects with varenicline include nausea and vomiting, headaches and sleep disorders such as abnormal dreams and insomnia. Patients may also feel drowsy, constipated, and agitated while taking the medicine. Varenicline has also been associated with causing skin reactions, such as the skin being sensitive to sunlight, and Stevens-Johnson syndrome, which is a rare skin condition that can cause painful blisters. Although not common, the medicine can also potentially cause kidney stones, kidney failure, and pancreatitis. Varenicline may also worsen patients who have psychiatric conditions such as depression and suicidal ideation. Therefore, careful monitoring of any mood changes and blood tests for examining kidney function may be required in susceptible patients.¹¹

Bupropion

Bupropion (Zyban®) is available as a 150 mg modified-release oral tablet. This is a prescription-only medicine that can be prescribed by a healthcare provider. When starting bupropion, the patient is on an initiation dose, which is usually started one to two weeks before the target quit date. The patient takes 150 mg daily for six days, then takes the maintenance dose of 150 mg twice a day for seven to nine weeks. Treatment is stopped if the patient is unable to quit at seven weeks. A maximum dose of 150 mg is considered in patients who are more prone to having seizures.^13,14

Mechanism of action

Bupropion’s mode of action is still inconclusive. It has been shown to prevent the reuptake of dopamine and noradrenaline (norepinephrine), which means that more neurotransmitters are available to trigger the brain’s reward system. The medicine has also been shown to block the effects of nicotine and could possibly prevent nicotine from releasing dopamine.¹⁵

Side effects

The most common side effects of bupropion include nausea and vomiting, headache, dizziness, insomnia, constipation, dry mouth, skin reactions, excessive sweating, increased blood pressure and heart rate, sore throat, blurred vision, and tremors. Bupropion may also increase the risk of seizures and worsen suicidal ideation. Therefore, it is generally not recommended for patients with a past history of seizures unless the benefits outweigh the risks. If epileptic patients do get prescribed bupropion, then careful monitoring for seizures and mood changes should be in place.^13,14

Other treatment options

Cytisinicline (Cytisine®) is another drug that can be used for smoking cessation. It is available as a 1.5 mg oral tablet, and is relatively new in the UK; therefore is not commonly prescribed.¹⁶

Summary

Smoking is a widespread issue that affects the whole of the UK. It can lead to damaging health conditions and increase mortality. Smoking cessation services are widely available to tackle this problem. It is not recommended to suddenly stop smoking, as it makes quitting harder. Therefore, medicines such as varenicline, bupropion, and NRT are commonly prescribed to help you quit. It is advised to speak to your GP or pharmacist, as they can help you with your quit-smoking journey.