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June 25, 2016

Pharmacotherapy for smoking cessation

The health benefits of smoking cessation are well documented. Smokers who quit reduce their risk of cardiovascular disease, lung disease, and cancer and increase their life expectancy substantially. While most smokers make several quit attempts before they succeed, about one in four who use any pharmacotherapy will eventually quit smoking. Evidence indicates that pharmacotherapy increases the odds of success and may reduce symptoms of withdrawal for those who smoke ≥10 cigarettes per day. While a few studies have shown that pharmacotherapy works even in the absence of psychosocial therapies, most studies show that combining pharmacotherapy and psychosocial treatments increases quit rates.

Three distinct types of pharmacotherapy have demonstrated efficacy for smoking cessation:

  • Nicotine replacement therapy (NRT) – By partially replacing the nicotine previously obtained from tobacco, NRT enables smokers to cease tobacco use and subsequently to withdraw from nicotine altogether. Several types of nicotine replacement products are on the market, including patch, gum, lozenge, and inhaler.
  • Bupropion is a monocyclic antidepressant that inhibits the reuptake of both norepinephrine and dopamine. The efficacy of bupropion in treating smokers is hypothesised to stem from its dopaminergic activity on the pleasure and reward pathways. Bupropion also has been shown to have an antagonist effect on nicotinic acetylcholine receptors. Thus, its mechanism of action likely is multifactorial.
  • Varenicline is a partial nicotine agonist/antagonist that selectively binds to the 4β2 nicotinic acetylcholine receptor. Varenicline both blocks nicotine from binding to the receptor (antagonist effect) and partially stimulates (agonist effect) receptor-mediated activity, leading to the release of dopamine, which reduces cravings and nicotine withdrawal symptoms.

The following recommendations and algorithm were developed by a panel of international experts in smoking cessation as a guide to assist clinicians in prescribing pharmacotherapy for smoking cessation.1

Factors to consider in prescribing pharmacotherapy

Selecting a particular type of pharmacotherapy should be guided by the following factors:

1. Evidence – The decision to prescribe smoking cessation medications needs to be based on evidence of effectiveness and safety.

2. Patient preference – Patient preference is important in facilitating adherence to the treatment protocol. Patient preference can be modified through an informed and shared decision-making process between the clinician and patient.

3. Patient experience – The patient’s expectation of success is very important in determining actual success. If the patient was successful with a particular medication for a period of time, it may be prudent to try the same medication again; if unsuccessful with a particular medication, then the medication probably should not be used again.

4. Patient needs – They include: Extent and severity of cravings, situations or times when cravings are strongest, triggers for smoking, specific hurdles to overcome, etc.

5. Patient history – Many patients have comorbidities which need to be taken into account. Smoking history, past quit attempts and experience with pharmacotherapy are all factors influencing pharmacotherapy choice.

6. Patient clinical suitability for pharmacotherapy – Some patients may not be suitable for pharmacotherapy interventions and potential contraindications need to be considered. Generally, pharmacotherapy would not be recommended for patients having a low level of nicotine dependence.

7. Potential drug interactions/side effects – Contraindications, use of other medications, and the side effect profile all need to be considered.

Combinations of pharmacotherapy

For some patients, choosing combination pharmacotherapy will increase their ability to stop smoking. Combination pharmacotherapy is indicated for patients based on five factors:

1. Failed attempt with monotherapy – The general principle is that intensity of medications should be increased when monotherapy has resulted in relapse.

2. Patients with breakthrough cravings – Breakthrough cravings may be an indication that more treatment is needed. An additional form of NRT or addition of NRT (as needed) to a non-NRT oral medication may be helpful. Combinations of NRT can be used for steady-state delivery (patch) and as needed (gum/lozenge).

3. Level of dependence – Highly dependent smokers are more likely to benefit from combination pharmacotherapy. It may be important to begin with combination pharmacotherapy for these individuals.

4. Multiple failed attempts – Multiple failed attempts may be an indication that more intensive therapy is needed. However, failed attempts may also be based on patient lack of commitment.

5. Patients with nicotine withdrawal – The combination of pharmacotherapies can be a helpful response for managing nicotine withdrawal symptoms.

Specific combinations of pharmacotherapy

When prescribing or recommending combinations of pharmacotherapy, first select combinations of NRT. Then, prescribe a combination of bupropion and NRT for more heavily dependent patients.*

1. Two or more forms of NRT – The use of two or more forms of NRT has the strongest evidence base and is the most commonly used form of combination therapy. There is a high level of confidence that this combination can be used safely and effectively.

2. Bupropion + NRT – Bupropion plus a form of NRT can be effective for some patients. This combination is generally used in more heavily dependent patients.

* Combination therapy with varenicline has shown promising results but has only been studied in small clinical trials to date.

Algorithm for Choosing Smoking Cessation Pharmacotherapy


1- Bader P, et al. An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts. Tob Control. 2009 Feb; 18(1):34-42.

2- Hurt RD, et al. Treating tobacco dependence in a medical setting. CA Cancer J Clin. 2009 Sep-Oct; 59(5):314-26.

3- Ebbert JO, et al. Varenicline for smoking cessation: efficacy, safety, and treatment recommendations. 2010 Oct 5; 4: 355-62.