Smoking & Health T reatment of T obacco D ependence (F . 17 WHO ICD X revision)

1. Smoking & HealthTreatment of Tobacco Dependence (F.17 WHO ICD X revision) Prof. Witold Zatonski, MD, PhD June 2005, Bulgaria

3. The introduction of tobacco smoke’s inhalation (cigarette smoking) into human habit, at the beginning of 20 century, changed global health picture

4. The mixture of 4000 chemical substances contained in tobacco smoke reaches all tissues and harm all life processes and body organs.

5. Tobacco smoking habit caused in 20 century systematic increase of morbidity and mortality on lung cancer, heart attack and chronic obstructive pulmonary disease (C.O.P.D)

6. Lung cancer, disease affects nearly exclusively tobacco smokers, changed the picture of cancer in developed countries in last century.

7. CANCER MORTALITY AMONG MEN IN USA IN YEARS 1930-1990 lung stomach Large bowel prostate pancreas liver

8. Tobacco smoke is cardiotoxic, it is the most important risk factor for heart attack, 80 % of M.I. before 50 years old among young and middle-aged adults is due to tobacco smoke.

9. Myocardial infarction risk among long-term smokers Myocardial infarction =15152, Control group =14800 52 countries Source: INTERHEART survey

10. Tobacco smoke is the main cause of Chronic Obstructive Pulmonary Disease (COPD)

11. Impact of tobacco smoking on FEV1 rate proper % of FEV1 Non-smokers Smokers Stopped smoking at 45 age Disability Stopped smoking at 45 age Death

13. Tobacco smoke exposure is the risk factor no.1 for small children’s health (age 0-4)

14. Health consequences of maternal smoking during pregnancy • Foetus growth restrain (low birth weight) • Intrauterine foetal anoxia • Brain and CNS development disturbances • Insufficient development of lungs function • Congenital defects • Miscarriage • Chronic respiratory diseases • Acute respiratory diseases • Asthma and its aggravation • Acute and chronic middle ear diseases • Sudden infant death

15. Tobacco dependence is a chronic, relapsingcondition that often requires repeated intervention.

16. Three Facets of Tobacco Addiction

17. INTERNATIONAL CLASSIFICATION OF DISORDERS - X REVISION (WHO) • F17 - Mental and behavioural disorders due to the use of tobacco • F17.0 Acute intoxication • F17.1 Harmful use • F17.2 Dependence syndrome • F17.3 Withdrawal state

18. SYMPTOMS OF TOBACCO DEPENDENCE • A strong desire or sense of compulsion to take tobacco, • Difficulties in controlling tobacco-taking behaviour • Persisting with tobacco use despite clear evidence of harmful consequences • Evidence of tolerance, • A withdrawal symptoms when tobacco use has ceased or been reduced

19. WITHDRAWAL SYMPTOMS • Craving for tobacco • Irrability or restlessness • Anxiety • Difficulty in concentrating • Insomnia • Increased appetite and increased body mass

20. There is a strong need to medicalize the act of smoking cessation. In many countries the treatment of tobacco dependence syndrome (F 17) has begun to be the element of physicians’ routine procedures.

21. DIAGNOSIS STEPS • Measure of exposition to tobacco smoke – carbon monoxide with smokerlyzer • Assess the nicotine dependence – Fagerstrom test • Assess the stage of changes (readiness to quit) • Assess the motivation

22. TREATMENT OF TOBACCO DEPENDENCE • GP’s suport and advice Preparation to quit smoking (guide: How to stop smoking) Pharmacotherapy Behavioural support • brief advice, • individual sessions, • groups sessions, • telephone counselling • self-help materials • Treatment of tobacco dependence as a life saving procedure

24. PHARMACOTHERAPY FOR TOBACCO DEPENDENCE • Short-acting Nicotine Replacement Therapy • Gum • Tablet/lozenge • Inhaler • Long-acting Nicotine Replacement Therapy • Patch • Brain-active medicine • Bupropion • Cytisine • Future medicines • Vareniciline • Rimonabant • Vaccine

25. An open label observational study of herbal cytisine (Tabex) as an aid to smoking cessation. Group under scientific supervision of Prof. Witold Zatoński M. Cedzyńska, K. Przewoźniak, dr E. Karpińska, dr n. med. D. Lewandowska, dr n. med. E. Bobek-Pstrucha, dr J. Jońska, dr J. Surowińska, U. Wojciechowska, J.M.Jaworski

26. History of herbal cytisine • The ‘60s- Russian scientists isolated cytisine from the seeds of the plant Cytisus Laburnum. They discovered that it is nicotine analog and its partial agonist (it activates the same receptors as nicotine). They proposed to use cytisine in tobacco dependency treatment.

27. The ‘70s-– Bulgarian pharmaceutical company introduced into Eastern European market (incl. Polish) the herbal cytisine - pills called Tabex, which contained 1.5 mg of cytisine. • The drug was at that time over counter (OTC).

28. The ‘70s-: First clinical studies • Abstinence during treatment (25 days): • 57,7%(Stojanov,Janaczkowa*) • 55% (D.Paun, J.Franze**),placebo34% • 12-month abstinence : • 21% (D.Paun, J.Franze**) • *Stoyanov S., Yanachkova M. A propos of the thearpeutic effectiveness and tolearance of tabex. Savremenna Medizina, 6, 1972 • ** Paun D., Franze J. Registration and consultations for smokers with chronic broncitis at the consulting department- Berlin. Documentation of the consultation department for smokers at the polyclinic of the hospital Friedrichshein”, Berlin

29. The 90’s. In Poland during re-registration there was requirement of completing documentation. • The drug become on the prescription only.

30. 1997 year. Pharmaceutical company Pfizer started studies on substance which is based on chemical structure and properties of cytisine (nicotine agonist) (Vareniciline).

31. Cytisine - characteristic • Alkaloid contained in plant Citisus Laborinum. • Nicotonic partial agonist (similar activity to nicotine) • May have a dual mechanism of efficacy in smoking cessation, both substituting for nicotine and blocking the effects of nicotine obtained by smoking.

32. Methods: * Entry criteria: ·regular smoker ·want to quit * Exclusion criteria: ·active ulcer ·uncontrolled hypertension ·schizophrenia * Treatment: 25 days (as specified by manufacturer) 1– 3 day 1 pill swallowed every 2 hours (6 pills) 4 – 12 day 1 pill swallowed every 2,5 hours(5 pills) 13 – 16 day 1 pill swallowed every 3 hours (4 pills) 17 – 20 day 1 pill swallowed every 4 hours (3 pills) 21 – 25 day 1 pill swallowed every 6 hours (2 pills) * No specified behavioural treatment * Self-help booklet * Routine Smoking Cessation Walk-In Clinic follow-up (visits after 1-2 weeks for variable period)

33. Methods: Data gathered • Baseline visit: • smoking history • FTND • motivation test • height/weight/blood pressure/ carbon monoxide • Follow-up visit (as attended): • weight/blood pressure/ carbon monoxide • adverse events • 3-month telephone interview: • duration • followed instruction for usage • self reported abstinence • adverse events • 12-month: • telephone interview (self-reported abstinence) • Invite to clinic (weight/blood pressure/ carbon monoxide)

34. patients entered: 436 patients interviewed at 3 months: 342 lost in follow-up: 94 took at least one pill: 315 never took Tabex: 27 quit: 119 quit: 1 quit smoking: 120 (3 months) (not even one puff) lost in follow-up: 9 patients interviewed at 12 months: 110 reported abstinence:70 validated abstinence at 12 months: 60

35. Patient characteristics • 56% women and 44 % men • 52% completed secondary educational level • Age (ave.) - 45 years • 56% started smoking between 18 and 25 . • 67% smoked > 20 years • 51% smoked > 20 cigarettes per day • 61% had 4 - 7 points in Fagerstrom test • 67% had quit attepmts in the past • 60% had 8 - 12 points in Schneider test

36. RESULTS

37. 12-WEEK RESULTSIntent to treat population: smoking cessation “not a puff” at 12 weeks, November 2003-March 2005 N=316 N=119

38. 12-MONTH RESULTS Intent to treat population: smoking cessation “not a puff” at 12 months, November 2003-March 2005 376 60

39. Characteristics, which promote success (12-week follow-up) Education level High motivation to quit smoking Lower nicotine dependency

40. SIDE EFFECTS AT 3 MONTHS - there were no serious side effects - 54/436 had at entry hypertension – no clinical changes in blood pressure value - 52/436 had history of ulcer * 2 subjects had “digestive tract afflictions” while on Tabex at interim visits * 11 subjects at 3 months interview stated they had discontinued Tabex due to “digestive tract afflications”

41. WEIGHT CHANGES AT 3 MONTHS

42. CONCLUSIONS • Tabex (cytisine) seems to be an effective drug in treatment of tobacco dependency. • Tabex (cytisine) appears to be safe and well tolerated, not inducing dangerous for health or life side effects. • The efficacy of cytisine appears significant, especially given the lack of behavioural support • Considering Tabex’s efficacy, safety and low price a large scale randomised, double blind trial is warranted.