Treating Tobacco Dependence Revised 2


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Treating Tobacco Dependence Revised 2

  1. 1. Treating Tobacco Dependence Stacy Seikel, MD Board Certified Addiction Medicine Board Certified Anesthesiology
  2. 2. Cigarettes <ul><li>Tobacco smoke – complex mixture of 4,000 chemicals with over 60 known carcinogens </li></ul><ul><li>Cigarette smoking – responsible for 1 in 5 deaths in USA (>400,000 deaths/year) </li></ul><ul><li>1965 to 1999 – Decline in smoking rate, 41% to 22.8% </li></ul><ul><li>Recent decrease in youth smoking </li></ul>
  3. 3. What Is Tobacco Dependence? <ul><li>Nicotine Dependence ≠ </li></ul><ul><li>Tobacco Dependence </li></ul>
  4. 4. Medical Consequences of Nicotine Dependence <ul><li>Negligible </li></ul><ul><li>Chronic nicotine medication use after stopping tobacco use likelihood of cardiac events </li></ul>
  5. 5. Medical Consequences of Tobacco Dependence <ul><li>Massively Overwhelming!! </li></ul>
  6. 6. Cigarette smoking is the chief avoidable cause of death in our society
  7. 7. Cigarettes Cause <ul><li>Lung Cancer </li></ul><ul><li>COPD </li></ul><ul><li>Heart Disease </li></ul><ul><li>Other Cancers </li></ul>
  8. 8. The Cost of Smoking <ul><li>442,000 deaths per years caused by smoking – 18% </li></ul>
  9. 9. Cigarette Smoking is NOT a Habit
  10. 10. What Is Tobacco Dependence? It Is a CHRONIC MEDICAL DISEASE.
  11. 11. FDA Drug Abuse Advisory Committee – June 9, 1997 <ul><li>“Tobacco dependence is a…[serious,] chronic, relapsing, life-threatening illness, that requires…long-term medical management.” </li></ul><ul><li>Curtis Wright, MD, PhD </li></ul><ul><li>Deputy Director, Div. of anesthetics, Critical Care, & </li></ul><ul><li>Addiction Drug Products </li></ul><ul><li>Food & Drug Administration </li></ul>
  12. 13. FACTORS UNDERPINNING TOBACCO DEPENDENCE <ul><ul><li>Psychological Dependency </li></ul></ul><ul><ul><li>Nicotine Addiction </li></ul></ul>
  13. 14. Factors that perpetuate smoking <ul><li>Cheap “high” </li></ul><ul><ul><li>Nicotine is a stimulant—releases HGH, epinephrine, serotonin, norepinephrine </li></ul></ul><ul><ul><li>Intravenous nicotine is indistinguishable from amphetamine for the first 10 minutes </li></ul></ul><ul><ul><li>Very rapid neuroadaptation (tolerance) to nicotine; smokers generally discount the stimulant effects </li></ul></ul>
  14. 15. Factors that perpetuate smoking <ul><li>Withdrawal symptoms </li></ul><ul><ul><li>Irritability, agitation, anxiety, hunger, difficulty concentrating </li></ul></ul><ul><ul><li>Relieved within a few seconds by smoking a cigarette </li></ul></ul><ul><ul><li>Symptoms are constant, uncomfortable, socially disruptive </li></ul></ul><ul><ul><li>Repeated episodes of withdrawal and relief of withdrawal induce avoidance of withdrawal </li></ul></ul>
  15. 16. Factors that perpetuate smoking <ul><li>Relief of dysphoric feelings </li></ul><ul><ul><li>Nicotine affects the ventral tegmental area and mesolimbic system as do most other drugs of addiction </li></ul></ul><ul><ul><li>Nicotine often substitutes for other (less socially acceptable) drugs </li></ul></ul><ul><ul><li>Very rapid CNS effects due to inhalation </li></ul></ul><ul><ul><li>Relief of withdrawal symptoms (anxiety) can be confused with relief of dysphoria (anxiety) </li></ul></ul>
  16. 17. Factors that perpetuate smoking <ul><li>Conditioned responses (“triggers”): Smoking is associated with a wide range of activities </li></ul><ul><ul><ul><li>Drinking alcohol, eating a meal, drinking coffee </li></ul></ul></ul><ul><ul><ul><li>Sexual activity </li></ul></ul></ul><ul><ul><ul><li>Completion of a project, escape from danger, end of the workday </li></ul></ul></ul><ul><ul><ul><li>Celebrations </li></ul></ul></ul><ul><ul><ul><li>Driving a car </li></ul></ul></ul><ul><ul><ul><li>Waiting </li></ul></ul></ul><ul><ul><ul><li>Seeing others smoke; smelling tobacco or smoke </li></ul></ul></ul>
  17. 18. ADDICTED SMOKERS <ul><li>Some are minimally dependent </li></ul><ul><li>Others are severely dependent </li></ul><ul><li>Genetic heritage affects dependence </li></ul>
  18. 19. ADDICTION <ul><li>CIGARETTES </li></ul><ul><li>10% not dependent </li></ul><ul><li>90% are dependent </li></ul><ul><li>ALCOHOL </li></ul><ul><li>90% not dependent </li></ul><ul><li>10% are dependent </li></ul>
  19. 20. Treating Tobacco Dependence <ul><li>Severe but treatable </li></ul><ul><li>70% of smokers visit a physician and 50% visit a dentist each year </li></ul><ul><li>Most smokers want to stop and 46% try to stop each year </li></ul><ul><li>Multicomponent therapy </li></ul>
  20. 21. Chronic Disease Nature of Tobacco Dependence <ul><li>Just like asthma, hypertension, or diabetes treatment, clinical deterioration is the rule and to be expected , when tobacco-dependence pharmacotherpy is stopped. </li></ul>
  21. 22. Interventionists <ul><li>Counselor </li></ul><ul><li>Nurse </li></ul><ul><li>CD Counselor </li></ul><ul><li>Respiratory Therapist </li></ul><ul><li>Psychologist </li></ul><ul><li>Physician </li></ul><ul><li>Dentist </li></ul><ul><li>Dental Hygienist </li></ul><ul><li>Nurse Practitioner </li></ul><ul><li>Physician Assistant </li></ul><ul><li>Occupational Therapist </li></ul>
  22. 23. Clinical in Practice Guideline Major Conclusions/Recommendation <ul><li>Tobacco dependence is a chronic condition </li></ul><ul><li>Effective treatments exist and all tobacco users should be offered treatment </li></ul><ul><li>Healthcare systems must systematize identification, documentation, and treatment of every tobacco user </li></ul><ul><li>Brief interventions are effective, but there is a strong dose response </li></ul><ul><li>Counseling effective </li></ul><ul><li>Pharmacotherapy is effective, and at least one should be prescribed </li></ul><ul><li>Treatments are cost-effective </li></ul>
  23. 24. Treating Tobacco Dependence Principles of Treatment <ul><li>Behavioral </li></ul><ul><li>Addictive disorders </li></ul><ul><li>Pharmacologic </li></ul><ul><li>Relapse prevention </li></ul>
  24. 25. Treating Tobacco Dependence Healthcare Professional’s Role <ul><li>Identify the smoker </li></ul><ul><li>Personalize the risks of smoking and benefits of stopping </li></ul><ul><li>Encourage patient to set stop date </li></ul><ul><li>Provide and monitor pharmacologic therapy </li></ul><ul><li>Follow-up and ongoing support </li></ul><ul><li>Referral </li></ul>
  25. 26. FDA-Approved Tobacco-Dependence Medications <ul><li>CONTROLLER MEDICATIONS </li></ul><ul><ul><li>Bupropion SR ((Zyban, Wellbutrin SR) </li></ul></ul><ul><ul><li>Nicotine Patch – OTC </li></ul></ul><ul><ul><li>Varenicline (Chantix) </li></ul></ul><ul><li>RELIEVER MEDICATIONS </li></ul><ul><li>Nicotine Inhaler </li></ul><ul><li>Nicotine Nasal Spray </li></ul><ul><li>Nicotine Polacrilex Gum (Nicorette) – OTC </li></ul><ul><li>Nicotine Polacrilex Lozenge (Commit) – OTC </li></ul><ul><li>Nicotine-8-Cyclodextrin – OTC </li></ul><ul><ul><li>Sublingual tablet </li></ul></ul>
  26. 27. NICOTINE MEDICATION SAFETY <ul><li>Nicotine does not cause lung cancer </li></ul><ul><ul><li>Tobacco smoke does </li></ul></ul><ul><li>Nicotine does not cause COPD </li></ul><ul><ul><li>Tobacco smoke does </li></ul></ul><ul><li>Nicotine does not cause acute MI </li></ul><ul><ul><li>Tobacco smoke does </li></ul></ul><ul><li>Nicotine does not cause acute vascular injury </li></ul><ul><ul><li>Tobacco smoke does </li></ul></ul>
  27. 28. Benefit of Prescribing At Least One Medication – Evidence-Based <ul><li>All FDA-approved medications suppress nicotine withdrawal signs and symptoms </li></ul><ul><li>Any one medication probability of stopping smoking </li></ul><ul><ul><li>2-3 x </li></ul></ul><ul><ul><ul><li>During medication treatment period </li></ul></ul></ul><ul><ul><ul><li>1 year after medication treatment-end </li></ul></ul></ul>
  28. 29. Benefit of Prescribing Two Medications – Evidence-Based <ul><li>Any pair of FDA-approved medications further probability of stopping smoking </li></ul><ul><li>50-100% over any one , effective medication </li></ul><ul><ul><li>During medication treatment period </li></ul></ul><ul><ul><li>1 year after medication treatment-end </li></ul></ul><ul><ul><li>Do not give Chantix with nicotine replacement therapy </li></ul></ul>
  29. 30. Nicotine <ul><li>Liquid in its native state </li></ul><ul><li>Distilled from burning tobacco and carried on tar droplets </li></ul><ul><li>Free (unprotonated) nicotine crosses biological membranes, therefore pH dependent </li></ul><ul><li>Inhalation -> peak arterial concentrations 2-4 x venous concentrations </li></ul><ul><li>Extensive first pass hepatic metabolism </li></ul><ul><li>Half-life 120 minutes </li></ul>
  30. 31. Treatment Pharmacotherapy <ul><li>First line </li></ul><ul><ul><li>Nicotine gum </li></ul></ul><ul><ul><li>Nicotine patches </li></ul></ul><ul><ul><li>Nicotine nasal spray </li></ul></ul><ul><ul><li>Nicotine inhaler </li></ul></ul><ul><ul><li>Nicotine lozenge </li></ul></ul><ul><ul><li>Bupropion </li></ul></ul><ul><ul><li>Varenicline </li></ul></ul><ul><li>Second line </li></ul><ul><ul><li>Clonidine </li></ul></ul><ul><ul><li>nortriptyline </li></ul></ul>
  31. 32. Nicotine Patch Therapy Background <ul><li>Placebo-controlled trials show doubling of stop rates </li></ul><ul><li>Growing literature showing a dose response </li></ul><ul><li>-50% median replacement with standard dose </li></ul><ul><li>Reduced smoking </li></ul><ul><li>while using nicotine patch </li></ul>
  32. 33. High Dose Patch Therapy Conclusions <ul><li>High dose patch therapy safe for heavy smokers </li></ul><ul><li>Smoking rate or blood continue to estimate initial patch dose </li></ul><ul><li>Assess adequacy of nicotine replacement by patient response or percent replacement </li></ul><ul><li>More complete nicotine replacement improves withdrawal symptom relief </li></ul><ul><li>Higher percent replacement may increase efficacy of nicotine patch therapy </li></ul>
  33. 34. High Dose Patch Therapy Dosing Based on Smoking Rate <ul><li><10 cpd 7-14 mg/d </li></ul><ul><li>10-20 cpd 14-22 mg/d </li></ul><ul><li>21-40 cpd 22-44 mg/d </li></ul><ul><li>>40 cpd 44+ mg/d </li></ul><ul><li>2 ppd = 2 patches </li></ul>
  34. 35. Nicotine Patch Therapy Clinical Use <ul><li>Individualize the dose and duration </li></ul><ul><li>Base initial dose on smoking rate or blood continine </li></ul><ul><li>Usual length of therapy: 6-8 weeks </li></ul><ul><li>Return visit or phone call at 1 or 2 week intervals </li></ul><ul><li>Adjust dose and determine length of Rx based on response </li></ul>
  35. 36. Bupropion Background <ul><li>Monocyclic antidepressant </li></ul><ul><li>Inhibits reuptake of norepinephrine and dopamine </li></ul><ul><li>May inhibit nicotinic ACH receptor function </li></ul><ul><li>Mechanism in helping smokers stop is not clear </li></ul><ul><li>May attenuate weight gain in abstinent smokers </li></ul>
  36. 37. Bupropion for Relapse Prevention Results <ul><li>58.8% smoking abstinence at week 7 </li></ul><ul><li>Relapse rate lower in active group through weeks 12 and 24 but not thereafter </li></ul><ul><li>Median time to relapse 156 d (active) vs. 65 d (placebo) </li></ul><ul><li>Smoking abstinence 47.7% (active) vs. 37.7% (placebo) through week 78 </li></ul><ul><li>Weight gain 3.8 and 4.1 kg (active) vs. 5.6 and 5.4 kg (placebo) at weeks 52 and 104 </li></ul>
  37. 38. Bupropion Summary <ul><li>Dose response efficacy in treating smokers </li></ul><ul><li>Attenuates weight gain </li></ul><ul><li>May be more effective than nicotine patch therapy </li></ul><ul><li>Delays relapse to smoking </li></ul><ul><li>Can be prescribed to diverse populations of smokers with expected comparable results </li></ul>
  38. 39. Medication strategies <ul><li>Partial receptor antagonist </li></ul><ul><ul><li>Varenicline (Chantix) </li></ul></ul>
  39. 40. Varenicline <ul><li>Approved May 11, 2006 by FDA (Pfizer) </li></ul><ul><li>Partial agonist at the nicotine receptor </li></ul><ul><li>High affinity for the α 4 β 2 subtype nicotine receptor </li></ul><ul><li>Trade name: Chantix </li></ul><ul><li>Derived from natural chemical cytisine, found in the plant “false tobacco” </li></ul>Foulds (2006) The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. J Clin Pract 60: 571–576
  40. 41. Orbach et al (2006) Drug Metabolism and Distribution T ½ excretion = 17 ± 3 hours
  41. 42. <ul><li>Nicotine receptor </li></ul><ul><li>Nicotine receptor </li></ul><ul><li>Powledge TM (2004) Nicotine as therapy.PLoS Biol 2(11): e404. </li></ul>Nicotine receptor
  42. 43. Foulds (2006) J Clin Pract 60: 571–576
  43. 44. N N = Nicotine
  44. 45. N
  45. 46. N Na+
  46. 47. N V V = Varenicline N = Nicotine
  47. 48. N V V = Varenicline N = Nicotine
  48. 49. N V
  49. 50. N V
  50. 51. N V
  51. 52. N V
  52. 53. N V
  53. 54. N V
  54. 55. N V Na+
  55. 56. Varenicline <ul><li>Partial agonist at the N-acetylcholine site—targets the α 4 β 2 receptor </li></ul><ul><li>Reduced craving and withdrawal symptoms </li></ul><ul><li>The most common adverse effects included nausea , headache, trouble sleeping, and abnormal dreams </li></ul><ul><li>No documentation of serious adverse effects </li></ul>Pfizer: data on file
  56. 57. Varenicline <ul><li>Continuous abstinence, weeks 9-12 </li></ul>Gonzales. JAMA 296:47-55 Varenicline <ul><ul><li>44 % </li></ul></ul>Bupropion <ul><ul><li>30 % </li></ul></ul>Placebo <ul><ul><li>17.7 % </li></ul></ul>
  57. 58. Varenicline <ul><li>Abstinence at 12 months of treatment </li></ul>Gonzales. JAMA 296:47-55 Varenicline <ul><ul><li>22.9% </li></ul></ul>Bupropion <ul><ul><li>16.1% </li></ul></ul>Placebo <ul><ul><li>8.4% </li></ul></ul>
  58. 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%
  59. 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%
  60. 61. Varenicline-adverse effects <ul><li>One report: exacerbation of symptoms in a patient with schizophrenia </li></ul><ul><li>One report: exacerbation of manic symptoms in a patient with bipolar disorder </li></ul><ul><li>One report: exacerbation of depression and psychosis in a patient with depression and a FH of bipolar disorder </li></ul><ul><li>One report: mixed episode and psychosis in a patient with depression </li></ul><ul><li>One report: cataracts </li></ul>
  61. 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%
  62. 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%
  63. 64. Varenicline-cessation Williams. 23:793-801 Varenicline Placebo Abstinence at week 52 37% 8%
  64. 65. Possible explanations for adverse psychiatric effects <ul><li>Varenicline is a dangerous drug </li></ul>
  65. 66. Possible explanations for adverse psychiatric effects <ul><li>Smoking is a dangerous behavior </li></ul><ul><ul><li>Nicotine has a prolonged effect on receptor function, causing profound and long-term alterations in mood, cognition, and behavior </li></ul></ul><ul><ul><li>Cessation of nicotine use results in poorly understood, but significant effects on mood, cognition, and behavior </li></ul></ul><ul><ul><li>Many of the adverse effects seen in patients using varenicline are due to long-term use of tobacco and nicotine, and nicotine withdrawal </li></ul></ul>
  66. 67. Varenicline dosing <ul><li>Begin while the patient is still smoking </li></ul><ul><li>“ Starter Pack” </li></ul><ul><ul><li>Initial dose = 0.5 mg at breakfast x days 1-3 </li></ul></ul><ul><ul><li>Then 0.5 mg @ breakfast and dinner x days 4-8 </li></ul></ul><ul><li>“ Continuation Pack” </li></ul><ul><ul><li>1 mg @ breakfast and dinner </li></ul></ul>
  67. 68. Varenicline dosing <ul><li>Since varenicline is a partial nicotine agonist, it is illogical to use a nicotine replacement product at the same time </li></ul><ul><li>There is inadequate data to advise for or against the simultaneous use of bupropion of nortriptyline for smoking cessation </li></ul><ul><li>Simultaneous use of antihypertensives, antidepressants, neuroleptics, and anticonvulsants appears safe </li></ul>
  68. 69. WHAT YOUR PATIENT NEEDS TO HEAR FROM YOU – 1 (At the Start of Treatment) <ul><li>Effective Treatment Takes Time </li></ul><ul><ul><li>Mean: 6-9 months </li></ul></ul><ul><ul><li>Range: 6 weeks to many years </li></ul></ul><ul><ul><li>25-35% need lifetime treatment </li></ul></ul><ul><li>Goals of Treatment </li></ul><ul><ul><li>Stop smoking </li></ul></ul><ul><ul><li>Suppress nicotine withdrawal symptoms </li></ul></ul>
  69. 70. WHAT YOUR PATIENT NEEDS TO HEAR FROM YOU -2 (At the Start of Treatment) <ul><li>Goals of Tapering </li></ul><ul><ul><li>Continue to be tobacco-free </li></ul></ul><ul><ul><li>Continue to blunt nicotine withdrawal symptoms </li></ul></ul><ul><ul><li>Thus: Medication Tapering is NOT a Down Escalator </li></ul></ul><ul><li>Keep Communication Lines Open </li></ul><ul><ul><li>Call me, your doctor, if you even think you may be having a problem </li></ul></ul>
  70. 71. Thank you.