1. 1 Advising smokers on optimum pharmacotherapy for smoking cessation University College London April 2014 Robert West

2. Declaration of interest I receive research funds and undertake consultancy for companies that develop and manufacture smoking cessation medications (Pfizer and J&J) I am co-director of the UK National Centre for Smoking Cessation and Training I am a trustee of the stop-smoking charity, QUIT My salary is funded by the charity, Cancer Research UK 2

3. Aims To summarise evidence on optimum use of pharmacotherapy to aid smoking cessation To use this evidence to give guidance on advice that should be given to smokers 3

4. How to stop smoking 4 Get Ready Go Keep going Decide on a ‘quit smoking rule’ Decide on a quit point Lay the ground work Apply the quit smoking rule Do what it takes to stick to the rule

5. 5 Addiction to cigarettes I really want to stop smoking: it’s costing me money and it will probably kill me Just smoke!

6. 6 The battle over time between resolve and urge to smoke Urge to smoke Time When the urge is stronger than resolve and cigarettes are available, a lapse will occur Resolve Strength of urge

7. 7 The role of treatment is to keep these lines as far apart as possible Urge to smoke Time Resolve Strength of urge

8. Support for smoking cessation Behavioural support –Advice, discussions, exercises designed to address social and psychological aspects of the problem Pharmacotherapy –Medicines (including nicotine products) designed primarily to reduce craving and withdrawal symptoms 8

9. The role of pharmacotherapy 1.Reduce the strength, duration or frequency of urges to smoke 2.Reduce unpleasant withdrawal symptoms 3.Reduce the pharmacological reward from smoking 9

10. Licensed medicines and e-cigarettes NRTtransdermal patch, gum, inhaler, lozenge, nasal spray, mouth spray, and oral film in varying doses and in combinations can be used for smoking reduction use for ≥8 weeks possibly starting before quit date Varenicline partial agonist binding with high affinity to  4  2 nAch receptor increase dose over 7 days then 1mg twice daily for ≥11 weeks or 23 weeks Bupropionunknown mechanism of action use for 8 weeks starting 1 week before quit date E-cigarettesMultiple variants from 1 st generation ‘cigalikes’ to ‘3 rd generation refillable, rechargeable bespoke devices Variable nicotine delivery

11. Aids used in most recent quit attempt 11 N=4,810 adults who smoke and tried to stop or who stopped in the past year Increase in use of e-cigarettes for quitting has been accompanied by a smaller reduction in use of other aids except behavioural support

12. Efficacy How many smokers who take the medicine stop smoking as a result in controlled settings? Randomised controlled trials –comparison with placebo and/or another medicine –intention to treat analysis with all those lost to follow up considered as having resumed smoking –follow up of at least 6 months –biochemical verification of abstinence –express difference as percentage point difference 12

13. ‘Real world’ effectiveness How many smokers who take the medicine stop smoking as a result compared with not using any medicine or who use another medicine? Observational studies –comparison of abstinence rates between smokers using different methods of stopping –cross sectional or prospective –adjust statistically for potential confounding variables 13

14. Efficacy in randomised controlled trials 14 Stead et al 2008, Cahill et al 2012, Cochrane Single NRT: N=51,265 Dual NRT: 4,664 NRT for ‘reduce to quit’: N=3,429 Pre-treat with NRT patch: N=424 Hughes et al 2008, Cahill et al 2012, Cochrane Varenicline: N=6,166 Bupropion: 11,440 Nortripyline: N=975 Cytisine: N=937 Bars represent 95% confidence intervals from meta-analyses

15. 15 Relative success rate in England by method of stopping Significantly better than no aid adjusting for confounding variables, p<0.001 Kotz et al (2013) Addiction, In Press

16. Relative effectiveness with specialist support 16 Brose et al, 2011 Thorax

17. Comparison between varenicline and NRT without specialist support 17 Results are similar after adjusting for potential confounding factors Kotz et al (2013) Psychopharm, Epub ahead of print

18. Real-world effectiveness of e-cigarettes 18 (1) E-cigarettes (N=464) (2) NRT over-the- counter (N=1922) (3) No aid (N=3477) (1) vs. (2) OR (95% CI) Adj. OR (95% CI) (1) vs. (3) OR (95% CI) Adj. OR (95% CI) % (N) Self- reported non- smoking 20.0 (93)10.1 (194)15.4 (535) 2.23 (1.70 to 2.93)*** 1.63 (1.17 to 2.27)** 1.38 (1.08 to 1.76)* 1.61 (1.19 to 2.18)** Adjusted for age, sex, social grade, time since quit attempt started, quit attempts in the past year, time spent with urges to smoke, strength of urges to smoke, abrupt vs. gradual quitting, time since last quit attempt started * time spent with urges, time since last quit attempt started * strength of urges to smoke, year of the survey. * p<0.05, ** p<0.01, *** p<0.001 Brown et al (submitted)

19. Conclusions Optimum treatment is specialist behavioural support plus either varenicline or dual form NRT (patch plus a faster acting form) Smokes should all be encouraged to get support with stopping Smokers using NRT bought OTC with no support do not currently appear to benefit Smokers using e-cigarettes with no support do seem to benefit If smokers are buying NRT OTC for stopping they should routinely be given guidance on optimum use: –stop abruptly rather than trying to cut down –dual form use –use as much as is needed to control cravings for at least 8 weeks 19