Efficacy of treatments for tobacco dependence

1. treatobacco.net Efficacy of treatments for tobacco dependence

2. Efficacy section Chairs Jamie Hartmann-Boyce The Cochrane Tobacco Addiction & Nicola Lindson Group, University of Oxford, UK Paul Aveyard University of Oxford, UK Michael Fiore Univ. of Wisconsin Medical School, Madison, Wisconsin, USA Jonathan Foulds Penn State University, Hershey, Pennsylvania, USA John Hughes University of Vermont, Burlington, USA Martin Raw Freelance consultant and University of Nottingham, UK Robert West University College London, London, UK

3. Efficacy of treatment • The purpose of the efficacy database is to provide information on effective treatments for tobacco dependence with established evidence bases (i.e. strength judged as A or B) • The key findings are based on the results of systematic reviews of the evidence from randomised controlled trials of treatment interventions, highlighting interventions that have been shown to produce a sustained increase in quit rates 6 months or more after treatment. • Recommendations are based on clinical practice guidelines and reflect the most recent update of the US guidelines in 2008. • References can be found at http://www.treatobacco.net/en/page_170.php for each of the key findings contained in this slide kit

4. Brief advice to quit (key finding 1) • Brief advice to quit from a primary care physician during a routine consultation increases the number of smokers stopping for at least 6 months. • Although the absolute effect is small (1–3%), this intervention can have a significant public health impact • It is important that physicians keep up-to-date records of the smoking status of all their patients, advise ALL smokers to stop on a regular basis and where possible offer them assistance with doing so, and repeat this advice as needed. • Where behavioural support programmes and medications are available these should be routinely offered.

5. Self-help materials (key findings 3 & 4) • Self-help interventions (generic, pre-printed, written or online materials giving advice about ways to quit) provided without personal support have a small effect on quit rates. Their impact is smaller and less certain than face-to-face interventions. • Self-help materials tailored to the needs of individual smokers assist quitting and are more effective than standard materials. • Materials may range from a brief guide and tip sheet to a structured material with exercises to guide quit attempts. Resources may include audio, videos, computer programmes, mobile phone applications, and websites. • Trials have been conducted with many types of smokers, using various types of materials offered alone, or provided as well as face-to-face advice or support. In experimental settings it has been difficult to demonstrate large or consistent long-term effects, but meta-analysis suggests a benefit.

6. Telephone based quitting resources (key finding 5) • Telephone based quitting resources increase quitting success rates. • Most quitlines provide access to counselling, and callers to quitlines who receive call-back counselling appear to benefit from more frequent contact. • Pooled data suggests a significant benefit from additional proactive telephone calls for callers to quitlines and of proactive telephone counselling for smokers not calling quitlines. • Quitlines also can provide or refer smokers to other treatments that are effective (e.g. nicotine replacement therapy).

7. Individual behavioural support (key findings 6 & 7) • In person behavioural support with multiple sessions of individual or group counselling aids smoking cessation. • From comparisons between studies, the components which are most likely to benefit smokers include problem solving and skills training. • The greater the amount of therapist–client contact the greater the chances of successful cessation. • Combining behavioural and medication treatments increases efficacy

8. Gradual versus abrupt quitting (key finding 8) • The traditional way to quit smoking has been to quit abruptly; however there are many smokers who have tried unsuccessfully to quit that way or feel that they would rather reduce their smoking first. • A Cochrane review found neither approach results in superior quit rates; however a subsequent, large RCT in which both studies used NRT before quit day has found evidence that abrupt quitting is significantly more effective. Nevertheless, the quit rates in the smoking reduction group were still respectable and much higher than would be seen if smokers quit without support. • Therefore, abrupt quitting should be encouraged for smokers who are willing to quit in this way; however reducing to quit should not be discouraged in smokers who otherwise would not make an attempt to quit at all. • Evidence on the efficacy of different behavioural reduction methods is not sufficient to recommend one particular method over another.

9. Relative effects of frontline pharmacotherapies (key finding 9) • Of the three front line therapies, combination nicotine replacement therapy and varenicline are equally effective and are more effective than single-form NRT or bupropion. • All three have been proven to be effective and have a low risk of harms. Figure 1. Absolute abstinence rates for smoking cessation drugs, based on data from network meta-analysis. Figure from: Hartmann-Boyce Jamie, Aveyard Paul. Drugs for smoking cessation BMJ 2016; 352 :i571

10. Nicotine replacement therapy(key findings 10-15) • Nicotine replacement therapies (NRT) aid smoking cessation. The different forms of NRT do not appear to differ in effectiveness. • NRT delivers nicotine at a lower concentration and more slowly than cigarettes, so logically any risks from nicotine alone should be lower than those from smoking. Addiction to NRT is rare. • More dependent smokers are more successful on 4 mg than 2 mg nicotine gum. • The relative effect of NRT does not depend on the amount of face-to-face behavioural support. • Combining the nicotine patch with an ad libitum type of NRT increases success rates. • Smokers who use nicotine gum or inhalator to reduce their cigarette intake reduce more and increase their future chances of successful quitting. There is no evidence to suggest that using NRT at the same time as smoking poses an additional safety risk.

11. Bupropion (key finding 17) • Bupropion is an efficacious aid to smoking cessation. • The efficacy of bupropion is not due to its antidepressant effects; it works equally well in smokers with and without a history of depression. • Doctors prescribing bupropion need to be aware of the contraindications to its use for people such as individuals with a history of a seizure disorder.

12. Varenicline (key finding 18) • Varenicline is an efficacious aid to smoking cessation • It is a nicotine receptor partial agonist which works both by reducing withdrawal and by blocking the effects of nicotine. • Pooled results show varenicline at standard dose more than doubles the chances of successful long-term smoking cessation compared with placebo. Most guidelines recommend it as a first line treatment. • Lower dose regimens also appear to confer benefits for cessation, while reducing the incidence of adverse events. • The most frequently recorded adverse effect of varenicline are nausea and sleep disruption, but mostly at mild to moderate levels and tending to subside over time. • Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.

13. Cytisine (key finding 19) • Cytisine is an efficacious aid to smoking cessation • Cytisine is a nicotine receptor partial agonist like varenicline. A product containing cytisine has been licensed and used as a smoking cessation aid in some Eastern European countries for more than 40 years but is not available in other countries. • Pooled results from 2 randomized controlled trials show a significant increase in long-term abstinence but more studies are needed. • Cytisine is currently much less expensive than varenicline.

14. Other pharmacotherapies (key findings 20 & 21) • Clonidine is efficacious but its usefulness is limited by a high incidence of side effects. Clonidine should be regarded as a second-line pharmacotherapy for smokers who have not been helped by any of the NRTs, bupropion or varenicline, or who have contraindications to their use. This pharmacotherapy is not licensed for smoking cessation. Its known adverse effects include hypotension and sedation. • Nortriptyline, a tricyclic antidepressant, is an efficacious aid to smoking cessation but its use is limited due to its adverse events profile. This pharmacotherapy is not licensed for smoking cessation in most countries. Known adverse effects include: constipation, sedation, urinary retention and cardiac problems. When taken as an overdose, nortriptyline could be fatal. These considerations lead to a lack of consensus over the use of nortriptyline as first- or second-line therapy.

15. Smoking cessation in pregnancy(key findings 24 & 25) • Smoking during pregnancy risks harming the fetus, and this knowledge motivates many women to quit. • Behavioural support is effective in helping pregnant smokers to stop. More intensive support or referral to a specialist service can increase quit rates over usual care or brief advice alone. There is also evidence to suggest that incentive-based smoking cessation programs, offering rewards such as lottery tickets, cash payments, vouchers and reimbursement of cash deposited by participants, result in higher long-term quit rates than alternative (non-contingent incentive) interventions. • There is insufficient evidence to assess whether NRT is effective or ineffective in pregnancy. Evidence on the use of bupropion and varenicline in pregnant smokers is too limited to draw conclusions on efficacy.

16. Hospital-based and preoperative interventions (key findings 26 & 27) • There is evidence that intensive preoperative behavioural smoking cessation interventions increase smoking cessation and reduce postoperative complications. • Behavioural support that is maintained post-discharge increases cessation rates for hospital inpatients.

17. Cessation in adolescents (key finding 28) • There is some evidence that behavioural support increases quit rates in adolescents, but no evidence that pharmacotherapy is effective. • Trials have tested a range of complex behavioural interventions, with some evidence supporting the use of motivational enhancement combined with psychological support using cognitive behavioural or stage based approaches.  • NRT and bupropion may be considered for the treatment of adolescents who have symptoms of nicotine dependence and who wish to quit, but direct trials of these medications have not detected a significant effect. • Trials of varenicline in adolescents have not been published.

18. Smokeless tobacco cessation (key finding 29) • Smokeless tobacco users should be offered behavioural support. There is limited evidence for pharmacotherapy. • Behavioural interventions incorporating telephone support, with and withoutoral examination and feedback about the specific risks of oral tobacco use, have been shown to assist quitting smokeless tobacco; however oral examination and feedback alone have not been found to be associated with a benefit. • Trials of bupropion have not found significant long-term effects on quitting smokeless tobacco, whereas trials of NRT have demonstrated heterogeneous effects. • Two trials of varenicline showed a significant long term effect.

19. Smoking cessation in people with depression (key finding 32) • Adding a psychosocial mood management component to a standard smoking cessation intervention increases long-term cessation rates in smokers with both current and past depression, when compared with the standard intervention alone. This successful smoking cessation can lead to improved mental health. • A review also found that adding bupropion also resulted in significantly increased quit rates for those who had suffered from depression in the past. • In the one trial that tested it, varenicline significantly increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.

20. Cessation in people with experiences of substance abuse (key finding 33) • Tobacco cessation interventions targeted at smokers in treatment and recovery for alcohol and other drug dependencies increases tobacco abstinence and do not appear to threaten sobriety. • A review found that providing people with alcohol or other drug dependence problems with standard smoking cessation pharmacotherapy treatment alone or with behavioural support resulted in higher smoking quit rates than usual care or placebo. • Eleven studies, including 2231 participants also found that the provision of tobacco cessation interventions did not make people more likely to return to using alcohol or other drugs.

21. Cost-effectiveness (key finding 34) • All smoking cessation interventions that have a detectable effect in raising quit rates are highly cost-effective in preserving life years. • US and UK analyses show that intervening to help smokers quit is very cost effective relative to other routinely used primary prevention and screening interventions because quitting can prevent a variety of chronic diseases including cancer, heart disease and pulmonary diseases. • Even the most intensive smoking cessation interventions are more cost effective than almost all other medical interventions and this occurs both in the general population and in special groups including hospitalized smokers and pregnant women.

22. Infrastructure (key finding 36) • Asking patients about tobacco use and documenting their tobacco use status increases the rate of clinician intervention. • Possible ways to ensure consistent documentation include adding smoking status to the list of vital signs, use of a smoking status sticker on charts or use of computerized reminder systems. • Checking tobacco use status may be done by members of the healthcare team other than the physician. • A review investigating the use of electronic health records to improve the delivery of smoking cessation treatment found that studies generally showed a positive effect on outcomes, such as documenting smoking status, giving advice to quit, assessing patient interest in quitting and providing assistance to quit, including referral.

23. Population-based approaches (key finding 37) • Tobacco control policies increase motivation to quit and number of quit attempts. • Increasing the price of tobacco has the most consistent evidence of effect. • A Cochrane review of mass media interventions for smoking cessation has found evidence that mass media campaigns can be effective in changing smoking behaviour in adults; however the evidence base is heterogeneous and of variable quality. • Similarly Cochrane reviews have been conducted evaluating legislative and institutional smoking bans. The legislative ban review provides evidence that the introduction of bans leads to improved health outcomes through a reduction in second-hand smoke. The institutional bans review found that settings-based policies reduce smoking rates in hospitals and universities; however overall the evidence base was deemed to be limited and in need of further high quality research. 

24. UK National Institute for Health and Care Excellence (NICE) guidelines • Identify people who smoke- people should be asked if they smoke by their healthcare practitioner , and those who smoke should be offered advice on how to stop • People who smoke should be offered referral to an evidence-based smoking cessation service • People who smoke should be offered behavioural support with pharmacotherapy by an evidence based smoking cessation service • People who seek support to stop smoking and who agree to pharmacotherapy should be offered a full course • People who smoke and have set a quit date with an evidence-based smoking cessation service should be assessed for exhaled carbon monoxide levels 4 weeks after their quit date • Secondary healthcare settings should ensure that a range of licensed nicotine‑containing products and stop smoking pharmacotherapies are available on site for patients, visitors and employees

25. UK National Institute for Health and Care Excellence (NICE) guidelines (cont.) • Smokers unwilling or not ready to stop smoking should be offered a harm reduction approach to smoking • Smokers unwilling or not ready to stop smoking should be advised that health problems associated with smoking are caused primarily by components in tobacco smoke other than nicotine • Smokers unwilling or not ready to stop smoking should be advised about using nicotine‑containing products and supported to obtain licensed nicotine‑containing products • 'Stop smoking' services should offer harm‑reduction approaches alongside existing approaches to stopping smoking in one step

26. US Public Health Service Guidelines (2008) • Both counselling and cessation medications by themselves are effective. Combining counselling and cessation medications boosts cessation rates additionally. • Intensive interventions are more effective than brief interventions and should be used when resources permit, but every smoker should be offered at least a minimal or brief intervention. • Smoking cessation interventions should help smokers recognize and cope with problems encountered in quitting (problem solving/skills training), should provide social support as part of treatment, and should encourage smokers to seek support from family and friends. • Where feasible, smokers attempting to quit with self-help material alone should be provided with access to support through a telephone hotline/helpline.

27. References and further reading • A full list of references for each finding can be found at http://www.treatobacco.net/en/page_170.php • A list of implications for further research can also be found at the above link