1. Philip Tønnesen,2005 Smoking cessation Philip Tønnesen, M.D, Dr.med.sci.

2. Philip Tønnesen,2005 Most smokers need help to quit Hughes JR et al. Smoking cessation among self-quitters. Health Psychol 1992; 11: 331-4 % Abstinent Days Post-Cessation 4030 20 10 0 3090180

3. Philip Tønnesen,2005 Basic principles Principle: quit cigarettes Use Nicotine (”NRT”) or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months

4. Philip Tønnesen,2005 Intensity of intervention Minimal (<3 minutes) is effective (A) Dose-response effect (person-to-person) (A) Four or more sessions especially effective (A)

5. Philip Tønnesen,2005 Intensity of intervention 43 studies Odds ratioSucces rate No contact1.011 % < 3 min.1.3 (1.01-1.6)13 %* 3-10 min.1.6 (1.2-2.0)16 %* > 10 min.2.3 (2.0-2.7)22 %*

6. Philip Tønnesen,2005 Intensity of intervention Number of sessions(n = 45) sessions:Odds ratioSucces rate 0-11.012 % 2-31.416 % * 4-81.921 % * >82.325 % *

7. Philip Tønnesen,2005 Nicotine Replacement Therapy from the Cochrane register. Success rates: Sustained for 1-year NRT versus placebo 1.73 (108 studies)(95 % CI, 1.62-1.85) Nicotine GUM 1.66 Nicotine PATCH 1.76 Nicotine NASAL SPRAY2.27 Nicotine INHALER:2.08 Nicotine SUBLINGUAL TABLET 1.73 Bupropion SR versus placebo 1.97 (16 studies)(95% CI, 1.67-2.34)

8. Philip Tønnesen,2005 Lung Clinic Study Tonnesen & Mikkelsen, 2000 Eur Respir J (N = 500) 1-year point prevalence

9. Philip Tønnesen,2005 Intensive group therapy and NRT. 12 month success. Data from Hjalmarson et al. Gum: : 29 % Nasal Spray: 27 % Inhaler: 28 % Placebo: 16 % Placebo: 15 % Placebo: 18 %

10. Philip Tønnesen,2005 Lung Health Study Continous abstinence (N=5,587)

11. Philip Tønnesen,2005 Lung Health Study: Point prevalence (N=5587)

12. Philip Tønnesen,2005 Guideline : NRT Dose: one piece of NRT equals one cigarette (except patch). Underdosing is common. Side effects: Local irritation of skin and mouth and throat. Nicotine overdosing: nausea, palpitations.

13. Philip Tønnesen,2005 Guideline : NRT Duration:Up to 3 months. Individually when needed up to 12 months, except patch which should only be used for 3 months. Major clinical problem: Underdosing New administration forms under development

14. Philip Tønnesen,2005 Treatment of nicotine dependency with antidepressants

15. Philip Tønnesen,2005 Different antidepressants Bupropion Nortriptyline SSRI MAO-inhibitors

16. Philip Tønnesen,2005 Bupropion amino-ketone agent inhibits re-uptake of dopamine and noradrenaline almost no effect on serotonin drug specific effect ? also effect of nortryptyline

17. Philip Tønnesen,2005 Randomized trial with Bupropion plus Nicotine Patch, NEJM 1999.

18. Philip Tønnesen,2005 NEJM 1999 Jorgenby 893 smokers 44 years 27 cigarettes/ day in 25 years CO = 29 ppm s-cotinine = 360 ng /ml FTQ = 7.5 1/3 tried Patch/ gum

19. Philip Tønnesen,2005 NEJM 1999 Jorgenby DESIGN: Treatment 9 weeks week Quit ______0__1*_2__3__4__5__6__7__8__9_ Weekly session of 15 min. with counseling 10 session (>150 min)

20. Philip Tønnesen,2005 NEJM 1999 Jorgenby DESIGN: Follow-up week ______10___12_______26___________52 8 telephone calls (Months 3-4-5-7-8-9-10-11)

21. Philip Tønnesen,2005 NEJM 1999, 12 months

22. Philip Tønnesen,2005 Point Prevalence * * * P<0.001. Statistical analysis tested at Weeks 3 & 7 only

23. Philip Tønnesen,2005 Bupropion, 2003,Tønnesen N = 707 527 Bupropion, 180 placebo 42 years old, 22-23 cig. per day, FTND:5 11 visits and 10 telephone calls 1-year sustained abstinence: 21 % versus 12 %

24. Philip Tønnesen,2005 COPD, BUP Chronic obstructive pulmonary disease 404 smokers 28 cigarettes/ day FTQ: 7.4 300 mg BUP/placebo for 12-weeks 11 centers

25. Philip Tønnesen,2005 Continuous quit rate in COPD patients with bupropion versus placebo (N = 404). * * *

26. Philip Tønnesen,2005 Side effects from bupropion used in smoking cessation Percentage Side effects Bupropion Placebo (n =399) (n =312) Insomnia 3920 Dry mouth 12 5 Worsening hypertension 1 <1 Discontinuation of drug 12 8 Urticaria 2 0 Seizure0.1 1 0

27. Philip Tønnesen,2005 Guideline: Bupropion dosage 150 mg AM for 7 days then 150 mg b.i.d. for 7-9 weeks quit after 1 week prescription only at least 8 hours between each dose if insomnia last dose in afternoon

28. Philip Tønnesen,2005 Conclusion 1: Bupropion Bupropion SR is an efficacious smoking cessation treatment Bupropion SR is a second line and also a first-line medication Bupropion is relative safe to use

29. Philip Tønnesen,2005 Nortriptyline 2 studies + 1 odds ratioSuccess 3 placebo arms1.012 % 3 active arms3.2 30 %(18-42) second-line drug due to adverse events

30. Philip Tønnesen,2005 Other drugs Different antidepressants: Nortriptyline SSRI: No effect

31. Philip Tønnesen,2005 Other methods ?

32. Philip Tønnesen,2005 Other methods Clonidine Aversion therapy/ Silver acetate Mecamylamine Hypnosis Acupuncture Herbal medicine Glucose Varinicline Rimonabant Nicotine vaccination

33. Philip Tønnesen,2005 Clonidine Alfa 2 -partiel agonist effect (central)(+anta) Antihypertensive agent Climacterial symptoms Migraine Smoking cessation

34. Philip Tønnesen,2005 Clonidine Tablets or Patches 0.1-0.75 mg/day Success rates: 5 studies placebo clonidine_____ 1.0 2.1 (1.4-3.2) 13.9 %25.6 % (17.7-33.6) Cochrane meta-analysis: 1.89 (95% confidence interval 1.30 to 2.74)

35. Philip Tønnesen,2005 <<<<<<Aversion therapy<<<<< Rapid smoking 12 studies The odds ratio (OR) for abstinence following rapid smoking compared to control was 1.98 (95% confidence intervals (CI): 1.36 to 2.90). Difficult to compare studies Smoke holding

36. Philip Tønnesen,2005 <<<<<<Aversion therapy<<<< ”US. Method”: no effect. Rapid smoking Smoke holding Silver acetate: 2 studies 1.05 (95% confidence interval 0.63 to 1.73) Unplesant taste when smoking

37. Philip Tønnesen,2005 <<<<<<<<Hypnosis<<<<<<< 9 studies Not more effective than no intervention Ohter studies did not show effect after 3 months

38. Philip Tønnesen,2005 <<<<<<Acupuncture<<<<<<< 22 studies 1-year success: 1.08 (95% confidence interval 0.77) No evidence that acupuncture should be used

39. Philip Tønnesen,2005 New: Varinicline Rationale: Direct nicotine receptor antagonist/partiel agonist On-going phase 2 studies

40. Philip Tønnesen,2005 New: Rimonabant Rationale: A Cannabinoid-receptor antagonist CB-1 CB-2 Appetitte pain Short term smoking cessation Prevent weight gain

41. Philip Tønnesen,2005 New: Nicotine vaccination Rationale: Antibodies against nicotine Nicotine bound in blood by antibody Lesser nicotine reach the brain Phase 1 and 2: human produce antibodies Vaccine tolerated

42. Philip Tønnesen,2005 Conclusion Clonidine second line drug Rapid smoking, mecamylamine and glucose should be tested In the pipeline under research: Varinicline Rimonabant Nicotine vaccination

43. Philip Tønnesen,2005 Overall conclusion Principle: quit cigarettes Use NRT or bupropion Break the psychological addiction Adjunctive behavioural support Bupropion for 7-9 weeks NRT for 2-4 months Doubles 1-year quit rate

44. Philip Tønnesen,2005 Smoking Reduction Tools: Cigarettes  + NRT long-term use Cigarettes  + Bupropion long-term use Cigarettes  + Snuff Less toxic cigarettes = product modification

45. Philip Tønnesen,2005 Smoking reduction Wennike, Tønnesen et al. Addiction 2003 411 smokers 24 cigarettes/day Motivation to reduce on 10-cm VAS: 9 Motivation to quit on 10-cm VAS: 5 Nicotine gum for up to 12 months

46. Philip Tønnesen,2005 Smoking reduction Wennike, Tønnesen et al. Addiction 2003 Reduction (sustained): ActivePlacebo 4-months14 %5 % (p<0.002) 1-year8.8 %1.5 % (p<0.001) 2-years6.3 %0.5 % (p<0.001)

47. Philip Tønnesen,2005 Smoking reduction Wennike, Tønnesen et al, Addiction 2003 Cessation (point): ActivePlacebo 4 months6.3 %0.5 % (p<0.001) 1-year11.2 %3.9 % (p<0.005) 2-years9.3 %3.4% (p<0.01) (2-year sust.)2.9 %0.0 % (p<0.015)

48. Philip Tønnesen,2005 Conclusion Smoking reduction promotes smoking cessation Smokeless tobacco (snus, chewing tobacco)?

49. Philip Tønnesen,2005 Cigarettes! Tobacco: It is the only product that kills the consumer, when used after the instructions of the producer!

50. Philip Tønnesen,2005