Pharmacological Interventions for Smoking Cessation

Mattias Neyt, Frank Hulstaert

A Cochrane overview of reviews

Smoking is the leading preventable cause of illness and premature death worldwide. In May 2013, the Cochrane Collaboration published an overview of reviews on smoking cessation with pharmacological interventions.¹ The main pharmacological interventions are nicotine replacement therapy (NRT), bupropion, and varenicline. The objectives included:

• How do NRT (single or combination), bupropion and varenicline compare with placebo and with each other in achieving long-term abstinence (six months or longer)?
• How do the risks of adverse and serious adverse events (SAEs) compare between the treatments, and are there instances where the harms may outweigh the benefits?

The study looked for reviews in the Cochrane Database of Systematic Reviews (CDSR) in The Cochrane Library (search conducted in November 2012). All selected Cochrane reviews included randomized controlled trials (RCTs). Most studies concentrated on adult smokers. The outcome measure for benefit is continuous or prolonged abstinence (at least six months) from the start of treatment. The study also looked at the incidence of serious adverse events associated with treatment. A network meta-analysis was conducted to compare the benefit of each treatment with the others and with placebo. Varenicline and bupropion were also compared for risks of serious adverse events.¹ A second network meta-analysis has split NRT into four subgroups: patch, gum, combination NRT and “other” NRT (i.e. inhalers, sprays, tablets and lozenges). Combination NRT is usually patch (slow-release) combined with a quick-action delivery formulation (e.g. gum or inhaler).

Results

Efficacy

All pharmacological interventions helped more people to quit than placebo:

• Single forms of NRT: odds ratio (OR) 1.84; 95% credible interval (CrI) 1.71 to 1.99
• Combination NRT: OR 2.73; 95% CrI 2.07 to 3.65
• Bupropion: OR 1.82; 95% CrI 1.60 to 2.06
• Varenicline: OR 2.88; 95% CrI 2.40 to 3.47

Bupropion and NRT showed equal efficacy (OR 0.99; 95% CrI 0.86 to 1.13). Varenicline was superior to single forms of NRT (OR 1.57; 95% CrI 1.29 to 1.91), and to bupropion (OR 1.59; 95% CrI 1.29 to 1.96) but not more effective than combination NRT (OR 1.06; 95% CrI 0.75 to 1.48). Combination NRT also outperformed single formulations.¹

Safety

Bupropion carries a risk of seizures of about 1 per 1000/1500 users. For both bupropion and varenicline a possible increased risk of neuropsychiatric disorders was reported and possible cardiovascular complications for bupropion. However, the researchers of the Cochrane review did not find evidence for this in the trials.¹

Conclusion of the Cochrane review

Pharmacological smoking cessation therapies (NRT single or combined, bupropion and varenicline) “have been shown in RCTs to improve the chances of quitting. […] Combination NRT and varenicline are equally effective. […] On current evidence, based on RCTs, none of the treatments appear to have an incidence of adverse events that would mitigate their use.”¹

smoking-cessation products on the Belgian market

As a reference, we give here the treatment costs and reimbursements of these products in Belgium. Prices were taken from the Belgium Centre for Pharmacotherapeutic Information (www.bcfi.be) and the National Institute for Health and Disability Insurance (NIHDI, www.riziv.fgov.be).

• Varenicline (Champix®): €246.99 for 12 weeks of treatment (starter pack (11 x 0,5mg and 14 x 1mg) of €49.95 for first two weeks and 140 tablets of 1mg (€197.04) for the remaining 10 weeks).
  Health insurance reimburses one box of 140 tablets (co-payment ≤€14.5) under specific conditions. The patient contribution is thus €64.45 (starter pack and co-payment).
• Bupropion (Zyban®): €128.14 for about 9 weeks of treatment (one starter pack of 30 tablets of 150mg (€42.20) and one package of 100 tablets of 150mg (€85.94)).
  Reimbursement of one package of 100 tablets (co-payment ≤€14.5) only for patients older than 35 with chronic obstructive pulmonary disease (COPD) and under specific conditions. The patient contribution is thus €56.70 (starter pack and co-payment).
• NRT: Products are available in multiple forms (gum, tablets, patches and inhalers) from different brands (Nicorette, Nicotinell, and Niquitin). Price range €7.10 (36 gums) to €61.26 (21 patches) per package.
  NRT and combination NRT are not reimbursed. However, “tabakstop/tabacstop” from the Foundation against Cancer offers a financial contribution for 6 weeks of NRT, a.o. to people entitled to preferential reimbursement or having an Omnio status.2

In comparison, smoking a pack of cigarettes per day during 10 weeks costs about €400 in Belgium.

References

1. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews 2013, Issue 5.Art.No.:CD009329.DOI: 10.1002/14651858.CD009329.pub2

2. http://www.tabakstop.be/rokers/hoe-stoppen/op-welke-terugbetalingen-heb-je-recht