The document discusses treating tobacco dependence and cigarette smoking as a chronic disease. It describes the harms of cigarette smoking and factors that perpetuate tobacco dependence, including nicotine addiction, withdrawal symptoms, and conditioned responses. It recommends treating tobacco dependence as a chronic condition using behavioral interventions, pharmacotherapy like nicotine replacement therapy, bupropion, and varenicline, and relapse prevention strategies. Clinical guidelines emphasize identifying and treating every tobacco user with effective medications and counseling.

1. Treating Tobacco Dependence Stacy Seikel, MD Board Certified Addiction Medicine Board Certified Anesthesiology

2. Cigarettes Tobacco smoke – complex mixture of 4,000 chemicals with over 60 known carcinogens Cigarette smoking – responsible for 1 in 5 deaths in USA (>400,000 deaths/year) 1965 to 1999 – Decline in smoking rate, 41% to 22.8% Recent decrease in youth smoking

3. What Is Tobacco Dependence? Nicotine Dependence ≠ Tobacco Dependence

4. Medical Consequences of Nicotine Dependence Negligible Chronic nicotine medication use after stopping tobacco use likelihood of cardiac events

5. Medical Consequences of Tobacco Dependence Massively Overwhelming!!

6. Cigarette smoking is the chief avoidable cause of death in our society

7. Cigarettes Cause Lung Cancer COPD Heart Disease Other Cancers

8. The Cost of Smoking 442,000 deaths per years caused by smoking – 18%

9. Cigarette Smoking is NOT a Habit

10. What Is Tobacco Dependence? It Is a CHRONIC MEDICAL DISEASE.

11. FDA Drug Abuse Advisory Committee – June 9, 1997 “Tobacco dependence is a…[serious,] chronic, relapsing, life-threatening illness, that requires…long-term medical management.” Curtis Wright, MD, PhD Deputy Director, Div. of anesthetics, Critical Care, & Addiction Drug Products Food & Drug Administration

13. FACTORS UNDERPINNING TOBACCO DEPENDENCE Psychological Dependency Nicotine Addiction

14. Factors that perpetuate smoking Cheap “high” Nicotine is a stimulant—releases HGH, epinephrine, serotonin, norepinephrine Intravenous nicotine is indistinguishable from amphetamine for the first 10 minutes Very rapid neuroadaptation (tolerance) to nicotine; smokers generally discount the stimulant effects

15. Factors that perpetuate smoking Withdrawal symptoms Irritability, agitation, anxiety, hunger, difficulty concentrating Relieved within a few seconds by smoking a cigarette Symptoms are constant, uncomfortable, socially disruptive Repeated episodes of withdrawal and relief of withdrawal induce avoidance of withdrawal

16. Factors that perpetuate smoking Relief of dysphoric feelings Nicotine affects the ventral tegmental area and mesolimbic system as do most other drugs of addiction Nicotine often substitutes for other (less socially acceptable) drugs Very rapid CNS effects due to inhalation Relief of withdrawal symptoms (anxiety) can be confused with relief of dysphoria (anxiety)

17. Factors that perpetuate smoking Conditioned responses (“triggers”): Smoking is associated with a wide range of activities Drinking alcohol, eating a meal, drinking coffee Sexual activity Completion of a project, escape from danger, end of the workday Celebrations Driving a car Waiting Seeing others smoke; smelling tobacco or smoke

18. ADDICTED SMOKERS Some are minimally dependent Others are severely dependent Genetic heritage affects dependence

19. ADDICTION CIGARETTES 10% not dependent 90% are dependent ALCOHOL 90% not dependent 10% are dependent

20. Treating Tobacco Dependence Severe but treatable 70% of smokers visit a physician and 50% visit a dentist each year Most smokers want to stop and 46% try to stop each year Multicomponent therapy

21. Chronic Disease Nature of Tobacco Dependence Just like asthma, hypertension, or diabetes treatment, clinical deterioration is the rule and to be expected , when tobacco-dependence pharmacotherpy is stopped.

22. Interventionists Counselor Nurse CD Counselor Respiratory Therapist Psychologist Physician Dentist Dental Hygienist Nurse Practitioner Physician Assistant Occupational Therapist

23. Clinical in Practice Guideline Major Conclusions/Recommendation Tobacco dependence is a chronic condition Effective treatments exist and all tobacco users should be offered treatment Healthcare systems must systematize identification, documentation, and treatment of every tobacco user Brief interventions are effective, but there is a strong dose response Counseling effective Pharmacotherapy is effective, and at least one should be prescribed Treatments are cost-effective

24. Treating Tobacco Dependence Principles of Treatment Behavioral Addictive disorders Pharmacologic Relapse prevention

25. Treating Tobacco Dependence Healthcare Professional’s Role Identify the smoker Personalize the risks of smoking and benefits of stopping Encourage patient to set stop date Provide and monitor pharmacologic therapy Follow-up and ongoing support Referral

26. FDA-Approved Tobacco-Dependence Medications CONTROLLER MEDICATIONS Bupropion SR ((Zyban, Wellbutrin SR) Nicotine Patch – OTC Varenicline (Chantix) RELIEVER MEDICATIONS Nicotine Inhaler Nicotine Nasal Spray Nicotine Polacrilex Gum (Nicorette) – OTC Nicotine Polacrilex Lozenge (Commit) – OTC Nicotine-8-Cyclodextrin – OTC Sublingual tablet

27. NICOTINE MEDICATION SAFETY Nicotine does not cause lung cancer Tobacco smoke does Nicotine does not cause COPD Tobacco smoke does Nicotine does not cause acute MI Tobacco smoke does Nicotine does not cause acute vascular injury Tobacco smoke does

28. Benefit of Prescribing At Least One Medication – Evidence-Based All FDA-approved medications suppress nicotine withdrawal signs and symptoms Any one medication probability of stopping smoking 2-3 x During medication treatment period 1 year after medication treatment-end

29. Benefit of Prescribing Two Medications – Evidence-Based Any pair of FDA-approved medications further probability of stopping smoking 50-100% over any one , effective medication During medication treatment period 1 year after medication treatment-end Do not give Chantix with nicotine replacement therapy

30. Nicotine Liquid in its native state Distilled from burning tobacco and carried on tar droplets Free (unprotonated) nicotine crosses biological membranes, therefore pH dependent Inhalation -> peak arterial concentrations 2-4 x venous concentrations Extensive first pass hepatic metabolism Half-life 120 minutes

31. Treatment Pharmacotherapy First line Nicotine gum Nicotine patches Nicotine nasal spray Nicotine inhaler Nicotine lozenge Bupropion Varenicline Second line Clonidine nortriptyline

32. Nicotine Patch Therapy Background Placebo-controlled trials show doubling of stop rates Growing literature showing a dose response -50% median replacement with standard dose Reduced smoking while using nicotine patch

33. High Dose Patch Therapy Conclusions High dose patch therapy safe for heavy smokers Smoking rate or blood continue to estimate initial patch dose Assess adequacy of nicotine replacement by patient response or percent replacement More complete nicotine replacement improves withdrawal symptom relief Higher percent replacement may increase efficacy of nicotine patch therapy

34. High Dose Patch Therapy Dosing Based on Smoking Rate <10 cpd 7-14 mg/d 10-20 cpd 14-22 mg/d 21-40 cpd 22-44 mg/d >40 cpd 44+ mg/d 2 ppd = 2 patches

35. Nicotine Patch Therapy Clinical Use Individualize the dose and duration Base initial dose on smoking rate or blood continine Usual length of therapy: 6-8 weeks Return visit or phone call at 1 or 2 week intervals Adjust dose and determine length of Rx based on response

36. Bupropion Background Monocyclic antidepressant Inhibits reuptake of norepinephrine and dopamine May inhibit nicotinic ACH receptor function Mechanism in helping smokers stop is not clear May attenuate weight gain in abstinent smokers

37. Bupropion for Relapse Prevention Results 58.8% smoking abstinence at week 7 Relapse rate lower in active group through weeks 12 and 24 but not thereafter Median time to relapse 156 d (active) vs. 65 d (placebo) Smoking abstinence 47.7% (active) vs. 37.7% (placebo) through week 78 Weight gain 3.8 and 4.1 kg (active) vs. 5.6 and 5.4 kg (placebo) at weeks 52 and 104

38. Bupropion Summary Dose response efficacy in treating smokers Attenuates weight gain May be more effective than nicotine patch therapy Delays relapse to smoking Can be prescribed to diverse populations of smokers with expected comparable results

39. Medication strategies Partial receptor antagonist Varenicline (Chantix)

40. Varenicline Approved May 11, 2006 by FDA (Pfizer) Partial agonist at the nicotine receptor High affinity for the α 4 β 2 subtype nicotine receptor Trade name: Chantix Derived from natural chemical cytisine, found in the plant “false tobacco” Foulds (2006) The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. J Clin Pract 60: 571–576

41. Orbach et al (2006) Drug Metabolism and Distribution http://dmd.aspetjournals.org/cgi/content/abstract/34/1/121 T ½ excretion = 17 ± 3 hours

42. Nicotine receptor Nicotine receptor Powledge TM (2004) Nicotine as therapy.PLoS Biol 2(11): e404. Nicotine receptor

43. Foulds (2006) J Clin Pract 60: 571–576

44. N N = Nicotine

45. N

46. N Na+

47. N V V = Varenicline N = Nicotine

48. N V V = Varenicline N = Nicotine

49. N V

50. N V

51. N V

52. N V

53. N V

54. N V

55. N V Na+

56. Varenicline Partial agonist at the N-acetylcholine site—targets the α 4 β 2 receptor Reduced craving and withdrawal symptoms The most common adverse effects included nausea , headache, trouble sleeping, and abnormal dreams No documentation of serious adverse effects Pfizer: data on file

57. Varenicline Continuous abstinence, weeks 9-12 Gonzales. JAMA 296:47-55 Varenicline 44 % Bupropion 30 % Placebo 17.7 %

58. Varenicline Abstinence at 12 months of treatment Gonzales. JAMA 296:47-55 Varenicline 22.9% Bupropion 16.1% Placebo 8.4%

59. Varenicline-adverse effects Gonzales. JAMA 296:47-55 Nausea Dreams Insomnia Varenicline 28% 10% 14% Bupropion 12.5% 5.5% 22% Placebo 8.4% 5.5% 12.8%

60. Varenicline-study drug discontinuation due to adverse effects Gonzales. JAMA 296:47-55 Nausea All causes Varenicline 2.6% 8.6% Bupropion 1.8% 15.2% Placebo 0.3% 9.0%

61. Varenicline-adverse effects One report: exacerbation of symptoms in a patient with schizophrenia One report: exacerbation of manic symptoms in a patient with bipolar disorder One report: exacerbation of depression and psychosis in a patient with depression and a FH of bipolar disorder One report: mixed episode and psychosis in a patient with depression One report: cataracts

62. Varenicline-discontinuation due to adverse effects, 1 year Williams. 23:793-801 Varenicline Placebo Adverse effects 26% 10% Lack of efficacy 0 5% Protocol deviations 2% 3% Lost to f/u 10% 15% Refusal to continue study 5% 16% All causes 46% 53%

63. Varenicline-adverse effects Williams. 23:793-801 Varenicline Placebo Nausea 40% 8% Dreams 23% 7% Insomnia 19% 9.5% Disgeusia 11% 2% Dizziness 8% 5% Any adverse effect 96% 83%

64. Varenicline-cessation Williams. 23:793-801 Varenicline Placebo Abstinence at week 52 37% 8%

65. Possible explanations for adverse psychiatric effects Varenicline is a dangerous drug

66. Possible explanations for adverse psychiatric effects Smoking is a dangerous behavior Nicotine has a prolonged effect on receptor function, causing profound and long-term alterations in mood, cognition, and behavior Cessation of nicotine use results in poorly understood, but significant effects on mood, cognition, and behavior Many of the adverse effects seen in patients using varenicline are due to long-term use of tobacco and nicotine, and nicotine withdrawal

67. Varenicline dosing Begin while the patient is still smoking “ Starter Pack” Initial dose = 0.5 mg at breakfast x days 1-3 Then 0.5 mg @ breakfast and dinner x days 4-8 “ Continuation Pack” 1 mg @ breakfast and dinner

68. Varenicline dosing Since varenicline is a partial nicotine agonist, it is illogical to use a nicotine replacement product at the same time There is inadequate data to advise for or against the simultaneous use of bupropion of nortriptyline for smoking cessation Simultaneous use of antihypertensives, antidepressants, neuroleptics, and anticonvulsants appears safe

69. WHAT YOUR PATIENT NEEDS TO HEAR FROM YOU – 1 (At the Start of Treatment) Effective Treatment Takes Time Mean: 6-9 months Range: 6 weeks to many years 25-35% need lifetime treatment Goals of Treatment Stop smoking Suppress nicotine withdrawal symptoms

70. WHAT YOUR PATIENT NEEDS TO HEAR FROM YOU -2 (At the Start of Treatment) Goals of Tapering Continue to be tobacco-free Continue to blunt nicotine withdrawal symptoms Thus: Medication Tapering is NOT a Down Escalator Keep Communication Lines Open Call me, your doctor, if you even think you may be having a problem

71. Thank you.