Exposure Reduction Therapy: Pharmacological Aids for Harm Reduction and Quit Assistance

1. Exposure Reduction Therapy:Pharmacological Aids for Harm Reduction and Quit Assistance Eric T. Moolchan, M.D. Teen Tobacco Addiction Research Clinic National Institute on Drug Abuse Intramural Research Program Susanne E. Tanski, MD AAP Center for Child Health Research University of Rochester School of Medicine

2. Overview • Importance of Tobacco Addiction • Why Pharmacological Treatment? • Integrating Current Medications • Harm Reduction and Quit Assistance • Optimizing Current Practice • Other Recommendations

5. The Cycle of Tobacco Addiction • 80-90% of smokers start in youth • 25% of adults smoke –80% of them addicted • 70% current smokers want to quit • 46% try on an annual basis try to quit • 3% achieve abstinence beyond 1 yr…almost 40% relapse within the following year (Wisconsin data)

9. Life Cycle Effects of Smoke Exposure Asthma Otitis Media Fire-related Injuries Cognitive Problems Influences to Start Smoking SIDS RSV/Bronchiolitis Meningitis Childhood Infancy Adolescence Nicotine Addiction Health Effects In utero Adulthood Low Birth Weight Stillbirth Cancer Cardiovascular Disease COPD Arch Pediatr Adolesc Med. 1997

10. Health Effects of Cigarette Smoking in Childhood/Adolescence • Decreased physical fitness • Cough and phlegm production • Increased incidence and severity of respiratory illness • Unfavorable lipid profile • Decreased lung growth and function • Precancerous DNA adduct formation • Addiction

11. Clinical Practice Guidelines for Youth • No evidence-based guidelines currently available • Adapted from adult guidelines • Developmentally appropriate? • 50% of 3,000,000 adolescent smokers have well-visits, • 3-5% effectiveness rate will yield 45,000-75,000 new ex-smokers annually!

12. Current Practice • Primary care physicians are more likely to focus on prevention than cessation treatment in adolescent smokers (Klein et al., 2001; Thorndike et al., 1999; MMWR, 1995) • Parental intervention relatively new

13. Pediatrician Intervention is Important • > 80% child exposure to tobacco in home is due to parental smoking • Pediatricians see 25% of the population of smokers through child visits – and smoking is highly heritable • Many parents see their child’s health care provider more often than their own (# QA increases with more episodes of advice) • Counseling interventions in the pediatric office setting have been successful: • Decreased number of cigarettes smoked and home cotinine levels • Increases in parent-reported smoke-free homes and parent-reported quit rates

14. Exposure Reduction Therapy • Use of pharmacotherapy for: • Situational abstinence • Short-term abstinence • Reduction of consumption (among Swiss students, reduction of 5 cigarettes/day during adolescence doubled the chance of being cigarette-free 3 years later) • Less exposure to ETS for families and children • Less household expenditures on tobacco Healthier Families

15. Approaching the Smoking Parent • 80% of adult and 54% of high school smokers want to quit • “Smoking isn’t good for you (or your child). You should quit, and I can help you. Are you ready?” • tailored interventions • Stages of Change model • A smoker may try to quit 5-7 times before achieving long-term abstinence …

16. Rationale for Pharmacological Treatment • Nicotine addiction • Mood and affect modulation • Cognitive decrements during withdrawal • Tobacco-free lifestyle coping skills take time to acquire

17. Tobacco Addiction is Real • Reinforcement • Tolerance • Withdrawal • Relapse

18. Tobacco Dependence • Adolescents experience symptoms of nicotine dependence prior to becoming daily smokers, and after exposure to only low doses of nicotine • Effects associated with dependence: • Increased numbers of brain nicotine receptors • Changes in regional blood glucose metabolism • EEG changes • Release of catecholamines • Tolerance • Physiological dependence

19. Tobacco Tolerance Modified Fagerstrom Questionnaire How many cigarettes a day do you smoke? Over 26 cigarettes a day (2), 16-25 (1), 1-15 (0), Less than 1 Do you inhale? Always (2), Quite often (1), Seldom (1), Never (0) How soon after you wake up do you smoke your first cigarette? Within the first 30 minutes (1), before noon (0), afternoon, evening Which cigarette would you hate to give up? First cigarette in the morning (1), any other (0) Do you find it difficult to refrain from smoking in places where it is forbidden (church, library, movies, etc.)? Yes, very difficult (1), Yes, somewhat difficult (1), No (0) Do you smoke if you are so ill that you are in bed most of the day? Yes, always (1), Yes, quite often (1), No, not usually (0), No, never (0) Do you smoke more during the first 2 hours than during the rest of the day? Yes (1), No (0)

20. Cigarette craving Anxiety Irritability Headache Insomnia Drowsiness Constipation Increased appetite Poor attention Impaired cognitive performance Decreased heart rate Tobacco Withdrawal Symptoms occur within hours of stopping smoking, and may persist for weeks

21. Treatment for Tobacco Dependence • Fallacy: most smokers quit “on their own” • Behavioral and Cognitive Behav. modalities • Increasing inter-cigarette interval/fading • Individual or Group CBT • Brief motivational interviewing • (Aversive therapy) • Contingency management • Pharmacotherapy • Nicotine Replacement Therapy • Sustained-release Bupropion • Other

22. Office-Based Interventions For Tobacco Smoking

23. Current Clinical Practice Guideline for Adults Public Health Service (PHS) guideline for adult smokers: • Screening • Intervention (combination of behavioral therapy and drug therapy) • Brief: 5As (Ask, Advise, Assess, Assist, Arrange)

24. The 5 A’s • National Cancer Institute/Public Health Service 5 A’s: Ask Advise Assess (Willingness to Quit) Assist Arrange follow-up

25. Ask • Obtain a smoking history from all patients and their parents at every visit • Current smoking and smoking during pregnancy • Include all settings (including relatives, child care settings…) • Document for future reference

26. Advise • Urge every tobacco user to quit • Provide information about smoking cessation and reducing children’s ETS exposure to all parents who smoke • Engage parent in a discussion about his or her smoking • Personalize health risks • Capitalize on educational/counseling opportunity

27. SSRC Addressing parental smoking in pediatric practice n=902 parents, 190 smokers from 2002 SCS-TC Pediatrics, 2003

28. Addressing parental smoking in pediatric practice N=877 pediatricians in the AAP

29. Assess willingness for quit attempt • Is the tobacco user willing to attempt quittingat this time? Behavior change occurs gradually, in stages, not all at once.

30. Assist • Help to set goals regarding smoking cessation and reducing ETS exposure • Inform about nicotine replacement, bupropion and consider prescribing them for harm reduction and/or quit attempts

31. SSRC Helping Parents Quit Smokingwith Effective Medications N=218 smoking parents

32. SSRC Rates of Pharmacotherapy Offered to Smoking Parents at Child Healthcare Visits N=143

33. Rates of Pharmacotherapy Offered to Smoking Parents at Child Healthcare Visits N=556 (direct patient care)

34. Currently Used Medications

35. Nicotine Replacement Therapy • Tobacco (not nicotine) responsible for most adverse health effects • Benefits of NRT outweigh the risks, even in smokers with cardiovascular disease: • Low risk of dependence compared to tobacco • Nicotine is not a significant risk factor for cardiovascular events, even in people with cardiovascular disease. • Studies to date: no increased health risks from potentially higher nicotine levels achieved from concomitant smoking and NRT • Both NRT and bupropion taken over long periods are safer than cigarette smoking

36. Nicotine Replacement Therapy • General principles (lower dose-response) • Nicotine Gum • Nicotine Patch (Transdermal) • Nicotine Nasal Spray • Nicotine Vapor Inhaler • Nicotine Lozenge • Combined Replacement Therapy

38. Nicotine patch and gum for smoking cessation plus CBT group counseling sessions • Comparison group: Placebo patch, placebo gum • Study participants: Youth ages 13-17 years recruited from the community • Primary end points: 30-day cessation/reduction at 3 and 6 months (via self report, CO, thiocyanate) • Integrated with lab studies

39. Pharmacological Recommendations

40. Nicotine Polacrilex Gum (OTC) Dosage • CPD < 25 use 2 mg, CPD  25 use 4 mg, Use enough (guidelines), Use long enough (for full 12 weeks) Side Effects: taste, jaw pain, nausea, dyspepsia, constipation, headache,… Advantages • Flexible dosing • Rapid blood level Disadvantages • Poor compliance and Under-dosing • Dietary influence

41. Nicotine Transdermal Patch (OTC) Dosage • 21mg, (16mg Day patch)- 14 mg, 7 mg, place the patch always at the beginning of the day Side effects: redness, itching, sleep disturbance Advantages • Good compliance • Sustained blood levels Disadvantages • Skin irritation

42. Nicotine Nasal Spray (Rx) Dosage • 1 dose yields 1 mg of nicotine (2 sprays, one/nostril) Side effects: cough, nasal /throat irritation Advantages • Flexible dosing • Rapid blood level (5-10 minutes) Disadvantages • Tolerance • Expensive

43. Nicotine Vapor Inhaler (Rx) Dosage • 10 mg/cartridge, 6-16 cartridges/day, MAX: 16/day, each puff yields about 13 μg, compared to 100μg per cigarette puff Side effects: throat irritation Advantages • Flexible dosing, “habit replacement” • Sensory cues (menthol, throat irritant) Disadvantages • ineffective if used alone

44. Nicotine Lozenge (OTC) Dosage • 1mg, 2 mg and 4 mg (delivering 2 mg of nicotine if properly used) Side effects: oral irritation Advantages • Flexible dosing • Rapid blood level (4mg lozenge give 25% higher blood level than 4 mg gum) • No chewing (discrete) Disadvantages • Under-dosing • Oral pH

45. Bupropion (Rx)Non-nicotine aid to smoking cessation • Chemically unrelated to nicotine • Atypical antidepressant • Pharmacodynamics: relatively weak inhibitor of the neuronal uptake of norepinephrine, serotonin, and dopamine – mechanism of action unknown, stimulant-like • T1/2: 21 hours, peak plasma concentrations within 3 hours • hydroxybupropion active metabolite

46. Bupropion (Rx) Efficacy demonstrated in clinical trials: • Hurt et al. 1997 • dose-response trial, 4 weeks, three doses (100,150,300) or placebo, abstinence last 4 weeks of treatment, treatment with 150 and 300 was more effective than placebo • Jorenby NEJM 1998 • bupropion alone vs Patch combo NRT • Hays 2001 • long-maintenance trial open label 300 mg x 7 weeks, then randomized to 300 mg or placebo for 1 year; at 6 mths continuous abstinence rates higher • Tonnesen 2003 • Bupropion in combination with counseling increased abstinence rates compared to placebo

47. Buproprion (Rx) Dosage • 150/300 mg at least 7 days before quitting Side effects • dry mouth, headache, sleep disturbance, dizziness Advantages Disadvantages • Need to pre-load • Contraindications: bulimia, anorexia, concurrent problem alcohol use

48. Combination Regimens • Patch + gum • Patch + lozenge • Patch + nasal spray/inhaler • Bupropion + patch • Bupropion + gum

49. Examples • 30 yo father of 3 week-old smokes 1ppd, FC within 15 minutes of waking, not ready to quit now–Approach? • 40 yo mother (30CPD) breastfeeding 2 month-old has repeatedly tried to quit, was able to quit for most of her pregnancy; relapsed soon after delivery-Approach?

50. Optimizing Current Practice • Clinician: best (judgment) practices, training, proper instruments • Tobacco intervention among highest ranking clinical procedures with regard to cost and impact ($2-3,000 for an addicted smoker to quit) • Organizational systems: health care system changes, office systems (VS for F/U) • Policy: reimbursement, performance measures…