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BIO Magazine - Smoking cessation drug effectiveness: a critical review Δεκέμβριος 2015
Δεκέμβριος 2015 No38

BIO Health

Smoking cessation drug effectiveness: a critical review
Smoking cessation drug effectiveness: a critical review


Even though the relationship between smoking and ill-health is well-documented, still many people start and continue to smoke. Public health campaigns have been made to promote this association between smoking and ill-health, and theories and research have been formulated and conducted to aid smokers quit and protect non-smokers as well. As pressures to quit smoking have been increasing especially during the last couple of decades, in the forms of stricter anti-smoking measures, at least in some countries, the need for smoking cessation aids for those smokers who want to quit becomes a necessity. Nowadays different aids to quit smoking are used by many smokers. This article serves as a review of the current smoking cessation strategies and drugs available. It includes details on the different methods to quit smoking, which can and are used by smokers who want to quit, either on the own or as part of smoking cessation clinics. The quitting methods reviewed consist of Nicotine Replacement Therapy (NRT), Bupropion hydrochloride (Zyban) and Varenicline (Chantix or Champix). A reference to other smoking cessation methods used by smokers and cessation clinics alike is also included. Keywords: smoking, nicotine, smoking cessation, NRT, Zyban, Chantix or Champix.

Putting smoking in a socio-historical context, there have always been restrictions on smoking with different emphases for different ‘target groups’ (e.g. Pierce et al, 1996). For example, children have always been a target group and women’s smoking has been restricted at different historical times and in different social contexts. After the 1960s a gradual change in attitudes towards smoking started to take place, in the Western world, especially after the documented associations between smoking and cancer.

Additional fuel to power a further change in attitudes and to protect others was the later ‘discovery’ of the link between disease and second-hand smoke. The second-hand smoke argument produced additional concern (as the health of non-smokers was now involved) changing the nature of the enforced anti-smoking measures (individual vs. common health). Thus the rationale behind new and stricter anti-smoking measures must be seen not only as a way to promote smoking cessation but most importantly to protect non-smokers from environmental tobacco smoke (ETS). Such pressures to quit have made many smokers seek help to quit with the use of different cessation aids. The article illustrates the different cessation methods available providing a review on each method.

Nicotine addiction

Nicotine, a liquid alkaloid (C10H14N2), the most active agent of tobacco and one of the basic ingredients in a cigarette (Harvey et al, 1992), is mainly responsible for the difficulties in smoking cessation, as it highly addictive. The stimulation of a number of areas of the brain can act as powerful reinforcement for the continuation of smoking. Nicotine has powerful effects as it interacts with nicotine cholinergic receptors, which are widely distributed in the brain, and exerts a biphasic, dose-dependent, stimulant/depressant effect on these receptors at cholinergic synapses (e.g. Harvey et al, 1992). 

Nicotine Replacement Therapy (NRT)

One of the most common therapies is nicotine replacement therapy (NRT). NRT involves the use of certain products in order to minimise the physiological dependence on nicotine, whereby nicotine gets into the body without the tar, carbon monoxide and other poisonous chemicals that are inhaled when smoking a cigarette (see Figure 1 below).  

Figure 1: Chemicals when smoking a cigarette

There are several NRTs available: nicotine polacrilex (gum), nicotine transdermal patch, nicotine nasal spray, nicotine inhaler, sublingual tablet and lozenge. A combined use of these products is more effective than using single agents alone. With NRT the withdrawal symptoms are reduced along with the cravings to smoke (e.g. Foulds & Ghodse, 1995). NRT delivers nicotine to the smokers’ brain in a much slower way compared with cigarettes. It helps to ease the urges to smoke that most smokers have right after quitting, rather than remove them totally. It gives the smoker the chance to break smoking cues in their daily lives, and thus providing a more comfortable exit from the smoking habit. In more detail:

Nicotine polacrilex (gum)

Nicotine gum delivers nicotine to the brain more quickly than the patch however, unlike the nicotine in tobacco smoke (7-8 seconds) the nicotine in the gum takes several minutes to reach the brain. Nicotine gum is not designed to be chewed like normal gum. Rather it is used in the "chew and park" method. The nicotine from the gum will make its way into the system via the blood vessels just under the inside layer of the oral cavity. The gum contains enough nicotine to reduce the urge to smoke and it is offered in 2mg and 4mg doses. It must be used appropriately in order to be effective. The gum has been shown to help control the weight gain commonly experienced after cessation (e.g. Molyneux, 2004).  

Nicotine patch

The nicotine patch releases a steady amount of nicotine in the body. Unlike the nicotine in tobacco smoke that passes almost immediately into the blood, the nicotine in the patch takes up to 3 hours to pass through the layers of skin and into the user's blood.

The patch must be worn all day, and cannot be put on and removed as a substitute for a cigarette. It must be worn only during the waking hours and must be removed during sleep. Wearing the patch reduces the chances of suffering from some of the main smoking withdrawal symptoms such as tenseness, irritability, drowsiness, and lack of concentration. Nicotine transdermal patches are available at 5mg, 10mg and 15mg and also 7mg, 14mg and 21mg per 24 hours. Some side effects may include: skin irritation, dizziness, sleep disturbances, headache, nausea, vomiting, muscle aches and stiffness.

Nicotine nasal spray

Nicotine is quickly absorbed through the nasal membranes and reaches the bloodstream faster than any other NRT product. This feature makes it attractive to some highly addicted smokers. The nicotine nasal spray is offered at 0.5mg per puff. A usual single dose is two sprays, one in each nostril. The most common side effects are nose and throat irritations.  

Nicotine inhaler

The nicotine inhaler consists of a plastic cylinder containing a cartridge that delivers nicotine. Although analogous in appearance to a cigarette, the inhaler delivers nicotine into the mouth, not the lung, and enters the body much more gradually than the nicotine in cigarettes. Each cartridge delivers up to 400 puffs of nicotine vapour. It takes at least 80 puffs to obtain the corresponding amount of nicotine delivered by one cigarette. The initial prescribed amount is individualized. The best effect is achieved by frequent, continuous puffing for 20 minutes. One cartridge will last for 20 minutes of continuous puffing and deliver 4 mg of nicotine; only 2 mg are actually absorbed. This is the equivalent of about 2 cigarettes. The maximum suggested dose is 16 cartridges per day. Side effects include irritation of the throat and mouth.

Nicotine lozenge

Nicotine lozenge comes in the form of a hard candy, and releases nicotine as it gradually dissolves in the mouth. Ultimately, the quitter will use fewer lozenges during the 12-week programme until he/she is totally nicotine-free. Nicotine lozenge is available in 2mg or 4mg doses. One lozenge is one dose; maximum dosage should not exceed 20 lozenges per day. Each lozenge will last about 20-30 minutes and nicotine will continue to leach through the lining of the mouth for a short period of time after the lozenge has dissolved. The most common side effects are: soreness of the teeth and gums, dyspepsia and throat irritation.

Bupropion hydrochloride (Zyban)

Bupropion hydrochloride (Zyban), a non-nicotine pill, accessible only by prescription, was also sold as an antidepressant under the name Wellbutrin. Treatment with bupropion begins while the user is still smoking, one week prior to the quit date. Treatment is then continued for 7 to 12 weeks, while duration of treatment is individualized. Dosing should begin at 150 mg/day given every day for the first 3 days, followed by a dose increase for most people to the recommended dose of 300 mg/day, starting on the 4 day of treatment. An interval of at least 8 hours between successive doses is advised.  People who have not made significant progress towards 

abstinence by the seventh week of therapy are unlikely to successfully quit during this attempt, and bupropion treatment should be stopped. Common side effects consist of insomnia, dry mouth and dizziness. Zyban is contraindicated in patients with a seizure disorder, in patients treated with wellbutrin, wellbutrin sr, or any other medications that contain bupropion because the incidence of seizure is dose dependent, and in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines). Also, women who are pregnant or breastfeeding and those under 18 should not use Bupropion. 

Unlike nicotine patches or nicotine gum, Zyban does not put more nicotine into the body. With patches or gum, the future quitter should stop smoking so that he/she doesn’t "overdose" on nicotine. With Zyban, the future quitter continues to smoke when he/she first starts taking the medication, ultimately reaching a quit-date, and continues taking the drug for a period of time after quitting. Based on a double blind controlled study comparing Zyban with an NRT patch, Zyban was superior to the patch in terms of 12-month follow-up abstinence (NICE Report, 2005). Yet, such findings must be viewed with caution as only a few studies have been conducted comparing NRT products with Zyban (and Chantix / Champix) making such studies a necessity, to produce further insights regarding treatment effectiveness and product choice. 

Varenicline (Chantix or Champix)

Chantix or Champix, Varenicline tartrate, is the newest prescription nicotine-free tablet form drug to quit smoking marketed by Pfizer, Inc. The active ingredient varenicline, works in two ways – by cutting the pleasure of smoking and blocking the effects of nicotine and by reducing the withdrawal symptoms that lead smokers to smoke (see also graphical illustration 1 below). The drug is not recommended for pregnant smokers, smokers younger than 18, or use with other smoking-cessation products. The tablet will be taken twice-daily for 12 weeks, a period that can be doubled in patients who successfully quit to increase the likelihood of long-term smoking abstinence. Common side-effects include: nausea, headache,vomiting, flatulence (gas), insomnia, abnormal dreams and dysgeusia (change in taste perception).

The effectiveness of Chantix (Chapmix) was tested based on controlled clinical trials, including a large sample (more than 3.500) of regular cigarette smokers. These studies were presented at an American Heart Association conference last year (can be viewed on-line at the FDA web-page). The results showed that the experimental group (treated with the drug) was superior in quitting than the control group (treated with placebo). Based on the results of two placebo-controlled studies, both Zyban and Chantix (Champix) were superior to placebo, but participants treated with Zyban were less likely to quit smoking compared to those treated with Chantix (Champix), as measured after a 12-week treatment (16% Vs 22% (study1) and 30% Vs 44% (study2) respectively). However, 50 weeks after treatment the differences (%) of participants who had used the two drugs and were still smoking abstinent were not statistically significant. Such findings indicate a short-term superiority of Chantix (Champix) over Zyban. However, further studies are needed to test drug effectiveness, and that long-term effectiveness in real-life setting remains unclear. 

Graphical illustration 1: How Chantix (Champix) works:

Nicotine from a cigarette stimulates the release of dopamine - a substance produced by the body which triggers feelings of pleasure.
When a smoker quits, the lack of nicotine leads to reduced levels of dopamine, causing feelings of craving and withdrawal.
Varenicline both blocks the nicotine receptors (reducing the addictive power of the drug) and triggers moderate dopamine release to alleviate withdrawal symptoms.
Other quitting methods

Other interventions available include aversion therapies, counselling and acupuncture (e.g. Taylor, 1999). Other forms of intervention to promote cessation are public health interventions including media campaigns (promotion of knowledge and/or anti-smoking images and social representations of smoking, to discourage smoking initiation and to encourage cessation) and anti-smoking legislation and measures (e.g. high taxation, bans on tobacco advertising, non-smoking policies at work and in public places) (e.g. WHO Report, 2005).


Smoking cessation has profound benefits regarding both the smokers’ and passive smokers’ health. Such smoking cessations aids provide a tool for the smokers who want to quit. Along with the smokers’ will-power and motivation to quit, they can prove to be effective, as a number of clinical trials have demonstrated. Still, to be most effective, smoking cessation products should be used in conjunction with a behaviour change programme and counselling. It is important with all types of medication to follow the doctor's orders and use the products only as prescribed and / or according to labelling.



  1. Foulds, J. & Ghodse, A.H. Treating Tobacco Dependence. Advances in Psychiatric Treatment 1: 116-123. (1995).
  2. Harvey, R.A. et al, Lippincott’s Illustrated Reviews: Pharmacology. Philadelphia: J.B Lippincott Company. (1992).
  3. Molyneux, , A. ABC of Smoking Cessation: Nicotine Replacement Therapy. British Medical Journal (328): 454-456. (2004).
  4. National Institute for Clinical Excellence (NICE) Report. (2005). Retrieved 18th of October 2007 from www.nice.org.uk
  5. Pierce, J.P. et al, The Psychology of Preventive Health. London: Routledge. (1996).
  6. Taylor, S.E. Health Psychology. 4th Ed. Boston: McGraw-Hill. (1999).
  7. WHO Report (2005). World Health Organisation: European Health for all Statistical Database.  Retrieved 8th of June 2007 from http://www.who.dk.hfadb. 
  8. www.fda.gov Retrieved 20th of October 2007
  9. www.ash.co.uk Retrieved 19th of October 2007

Dr. Penelope Louka, BA, MSc, PhD

Health Psychologist

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