Systematic review
Drugs for smoking cessation
Systematic review
|Updated
We have summarized results from three high quality systematic reviews and 26 randomized controlled trials.
Key message
Smoking is a risk factor for several diseases, including cancer, respiratory diseases and cardiovascular diseases. In Norway, about 21 % of the population smoke. There are two main types of smoking cessation programmes; counselling and drug assisted treatment. The two approaches can also be combined. This project is focused drug assisted treatment only. There are two drugs on the Norwegian marked for use in smoking cessation; varenicline (Champix® or Chantix®) and bupropion (Zyban®). In addition there are several options for nicotine replacement therapy. We have summarized the available research on the efficacy and safety of drugs for smoking cessation. We have considered comparisons between different drugs and between drugs and placebo. The review is intended to be used as part of the documentation basis for new national practice guidelines for smoking cessation in primary care. We have summarized results from three high quality systematic reviews and 26 randomized controlled trials. Our endpoint was smoking cessation (measured as 7-day point prevalence or continuous abstinence) after 12, 24 and 52 weeks and side effects (serious adverse events, nausea, weight gain, insomnia, headache, abnormal dreams, fatigue, psychiatric symptoms, anxiety and dizziness). Conclusion: • Drugs for smoking cessation probably improve smoking cessation after 52 weeks compared with placebo.• Varenicline will improve smoking cessation after 52 weeks compared to bupropion.• We are uncertain whether there is any difference between different nicotine replacement therapies in terms of achieved smoking cessation.• Combined use of two nicotine replacement products may improve smoking cessation than use of one product.• Drugs seem to lead to more side effects than placebo.• The documentation is too insufficient for us to determine if the drugs cause serious side effects.
Summary
Background Smoking is a risk factor for several diseases, including cancer, respiratory diseases and cardiovascular diseases. In Norway, about 21 % of the population smoke. There are two main types of smoking cessation programmes; counselling and drug assisted treatment. The two approaches can also be combined. There are two drugs on the Norwegian marked for use in smoking cessation; varenicline (Champix® or Chantix®) and bupropion (Zyban®). In addition there are several options for nicotine replacement therapy. On assignment from the Norwegian Directorate of Health, we have summarized the available research on the efficacy and safety of drugs for smoking cessation. We have considered comparisons between different drugs and between drugs and placebo. This systematic review is intended to be used as part of the documentation for new national guidelines for smoking cessation in primary care. Method We searched for systematic reviews in relevant bibliographic databases in May 2009. The search was limited to the period from January 01, 2007 to May 14, 2009. In addition we systematically searched for randomized controlled trials (RCT) in the period from January 01, 1995 to April 28, 2009. Pharmaceutical companies, who market the relevant drugs in Norway, were asked to submit literature relevant to our objective. Two people went through all the titles and abstracts and selected articles independent of each other. We ordered the relevant systematic reviews and primary articles in full text, quality assessed them by the checklists, compiled the results and graded the overall documentation. We summarized the results for efficacy and safety of the drugs for the following outcomes: Smoking cessation at 12, 24 and 52 weeks (measured as 7 days point-prevalence and/or continuous abstinence) Serious side effects (such as death, hospitalisation, disability, cancer, emotional liability, chest pain) Side effects (nausea, weight gain, insomnia, headache, abnormal dreams, fatigue, psychiatric symptoms (such as fear, anxiety, depression), dizziness) The analysis of the drugs compared with placebo, were taken from the included systematic overviews. We performed separate analysis for drugs compared with each other based on results from the randomized controlled studies. The population was people who smoke, and we also conducted separate analyses for adolescents and for people with various diseases. Results The literature search for systematic reviews identified 62 references. Three of the references fulfilled the inclusion criteria and are included in the report. The literature search for randomized controlled trials identified 1932 references. Twenty-two of the references fulfilled the inclusion criteria and are included in the report. We included two studies from the documentation that we received from the pharmaceutical companies. Furthermore, we found two studies when reviewing the systematic reviews so that the total number of included randomized controlled trials was 26. Drugs for smoking cessation versus placebo Smoking cessation after 24 to 52 weeks: • Nicotine replacement therapy probably will improve smoking cessation after 24 to 52 weeks compared with placebo.• Bupropion probably will improve smoking cessation after 24 til 52 weeks compared with placebo.• Varenicline will improve smoking cessation after 24 to 52 weeks compared with placebo. Side effects: • The systematic reviews suggest that there are more side effects associated with drugs than with placebo. It is not clarified whether drugs cause serious adverse events. Drugs for smoking cessation directly compared with each other: Smoking cessation after 52 weeks: • The documentation is too insufficient for us to determine if whether there are differences between bupropion and nicotine replacement therapies.• Varenicline probably will improve smoking cessation compared with nicotine patch.• Varenicline will improve smoking cessation compared with bupropion. Side effects: • Bupropion may give lower weight gain than nicotine replacement therapy, it is perhaps fewer who experience abnormal dreams, but there might be more people who experience insomnia.• Varenicline may lead to more nausea, fatigue and dizziness than nicotine patch.• Varenicline causes less insomnia and probably more weight gain than bupropion, and probably to more nausea. It is perhaps little or no difference when it comes to headaches, fatigue, anxiety and dizziness Nicotine replacement therapy compared with each other Smoking cessation after 52 weeks: • Only for nicotine patch compared to nicotine patch combined with nicotine spray did we find statistical significant results in favour of the combination after one year. Other comparisons show no statistically significant differences after one year, or it lacks documentation for our endpoint in the studies. For some comparisons, we did not find studies. Side effects: • The documentation of side effects is insufficient. Weight gain was the side effect that the majority of studies have reported, but the results show that there might be little or no difference between the different nicotine replacement therapies. Discussion Although the effect estimates for smoking cessation shows that all drugs are effective it is important to note that approximately 10% of the participants have stopped smoking after 1 year using placebo, while approximately 16%, 18% and 26% have stopped smoking by using nicotine replacement therapy, bupropion and varenicline. This means that about 80% still smoke even after using drugs for smoking cessation. Drugs seem to give more side effects than placebo. However, the documentation for the side effects is of consistently low or very low quality, which makes the effect estimates uncertain. It can also be difficult to determine whether side effects are a consequence of the drugs or a consequence of loss of nicotine (physical dependence). There is a need for registration of side effects to intercept rare adverse events. If the drugs give a similar effect and side effect profile, will the choice of drug depend on the price, the smokers’ preferences for prescription versus non-prescription drugs and what drugs they might have tried earlier. It should also be examined if drugs for smoking cessation are more effective than e.g. exercise and therapy. Conclusion Drugs for smoking cessation probably improve smoking cessation after 52 weeks compared with placebo.• Varenicline will improve smoking cessation after 52 weeks compared to bupropion.• We are uncertain whether there is any difference between different nicotine replacement therapies in terms of achieved smoking cessation.• Combined use of two nicotine replacement products may improve smoking cessation than use of one product.• Drugs seem to lead to more side effects than placebo.• The documentation is too insufficient for us to determine if the drugs cause serious side effects.