1. Smoking Cessation and Chronic Mental Illness CSAM May 15, 2009 David Kan, M.D. E-mail: David.Kan2@va.gov San Francisco VA Medical Center Asst. Clinical Professor, UCSF

2. Overview Epidemiology Nicotine & Tobacco Aka: Dr. Jekyll & Mr. Hyde Smoking Cessation Psychosocial Pharmacological

3. Epidemiology Total 47.2 million adults (24.1%) were current smokers 24.8 million men and 22.4 million women. 82.4% of all smokers were everyday smokers Age The highest rate of smoking was in 18-24 year olds: 27.9% and 25-44 year olds: 27.5%. Smoking rates drop with Age Source: CDC 1998 Survey

4. Epidemiology Ethnicity Native Americans/Alaska Natives: 40%, 25% of Caucasians and 24.7% of African Americans smoke. Hispanics: 19.1% and Asians/Pacific Islanders:13.7%. Education and income More Education = Less Smoking More Income = Less Smoking Source: CDC Survey 1998

5. Smoking and Mental Illness, Lasser, et al. JAMA. 2000;284:2606-2610.

6. Smoking Rates & Mental Illness In general 2x Non-Mentally Ill Diagnosis In Past Month US Population, % Current Smokers, % Lifetime Smokers, % Quit Rate, % Major Depression 4.944.760.426 Non Affective Psychosis 0.245.3 0 Drug Abuse or Dependence 167.987.522.4 Bipolar Disorder 0.960.681.825.9 National Comorbidity Study – 1989 US NHIS

7. Nicotine vs. Tobacco

8. Nicotine Ideal CNS Drug Very Effective Very Safe

9. Neurochemical Effects Slide Courtesy: David Sachs, M.D.

10. Why Cigarettes? Ideal Drug Delivery System Very Rapid Delivery High Dose Highly Concentrated

11. What is the Problem with Cigarettes? Toxic Delivery System

12. SMOKE is the PROBLEM NOT NICOTINE!!!

13. Smoking Related Illness 1/3 rd of Smokers will die prematurely of tobacco-related illness

14. Tobacco – Drug Interactions Pharmacokinetic Polycyclic aromatic hydrocarbons (PAHs) are some of the major lung carcinogens found in tobacco smoke PAHs - potent inducers of the hepatic cytochrome P-450 (CYP) isoenzymes 1A1, 1A2, and, possibly, 2E1 CYP 1A2 – largest effect Kroon, L “Drug interactions with smoking.” Am J Health Syst Pharm. 2007 Sep 15;64(18):1917-21

15. Tobacco – Drug Interactions Drugs Affected Clozapine Fluvoxamine Olanzapine Caffeine Tacrine UP TO 50% REDUCTION IN BLOOD LEVELS Kroon, L “Drug interactions with smoking.” Am J Health Syst Pharm. 2007 Sep 15;64(18):1917-21

16. Tobacco – Drug Interactions Hormone Contraceptives Increased risk of Stroke and Heart Attack Inhaled Corticosteroids Decreased Efficacy Kroon, L “Drug interactions with smoking.” Am J Health Syst Pharm. 2007 Sep 15;64(18):1917-21

17. What About Quitting?

18. Tobacco Dependence In Perspective Approximately 35% try to quit each year 70% to 80% try to quit “cold turkey” Most Relapse — 95% Cold turkey quit rates at 1 year are 5% Physician-assisted quit rates (short-term counseling + medications) at 1 year are 10% to 30% Fiore MC, et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: US Dept of Health & Human Services. Public Health Service. June 2000. (www.surgeongeneral.gov/tobacco/default.htm)

21. Disease Model of Tobacco Dependence Acute Disease Short-Term Disorder Severe Sudden in Onset Single, Time-limited intervention Examples: Common Cold Broken Bone Chronic Disease Long-Term Disorder Periods of relapse and remission Requires ongoing rather than acute care Examples: Diabetes Hypertension Addiction Smoking!

23. Psychiatric Conditions 2x as likely to smoke Depressed Smokers More Depression less likely to quit Psychiatric Conditions Data mixed or lacking as to long-term outcomes Many studies show interventions work as well as with those not mentally ill Ranny, et al: Systematic review: smoking cessation intervention strategies for adults and adults in special populations. Ann Intern Med. 2006 Dec 5;145(11):845-56. Epub 2006 Sep 5. Review.

24. Substance Abuse Alcohol & Tobacco Alcohol Use Triggers / exacerbates tobacco use Quitting both led to higher quit rates for both Joseph, AM et al A randomized trial of concurrent versus delayed smoking intervention for patients in alcohol dependence treatment. Stud Alcohol. 2004 Nov;65(6):681-91

25. Indications for Longer/More Intensive Treatment High Nicotine Dependence FTQ >5 High Serum Cotinine >250ng/ml Depression Beck Depression Inventory > 9 Smoker in Household Decreases chances by 50% Sachs DPL. “Tobacco Dependence: Pathophysiology & Treatment” Pulmonary Rehabilitation Guidelines to Success, 3 rd Edition 2000:261-301

26. Indications for Longer/More Intensive Treatment Smoking Initiation at Younger Age <17 years old Heavy Smoker >1 Pack Per Day # of Prior quit attempts Alcohol or Drug Abuse Psychotic Spectrum Illness Sachs DPL. “Tobacco Dependence: Pathophysiology & Treatment” Pulmonary Rehabilitation Guidelines to Success, 3rd Edition 2000:261-301

27. Treatment Recommendations

28. Psychosocial Interventions Counseling Behavioral Therapy Quit Line (1-800-NO-BUTTS) Motivational Enhancement

29. FDA Approved Medications CONTROLLER MEDICATIONS Bupropion SR (Zyban, Wellbutrin SR, Wellbutrin XL) Nicotine Patch Varenicline (Chantix) RESCUE MEDICATIONS Nicotine Inhaler Nicotine Nasal Spray - Fastest Nicotine Polacrilex Gum (Nicorette) – pH dependent Nicotine Polacrilex Lozenge (Commit) – pH dependent

30. Slide Courtesy: David Sachs, MD

31. Success Strategies Combined Strategies Behavioral + Medication Always at least 1 controller Almost always need Rescue

32. Nicotine Replacement “Clean vs. Dirty” 1 Start with Patch Add lozenge, gum, nasal spray, inhaler Target 30-60 days smoke free prior to tapering Taper short acting first Weeks to YEARS! 1. Peter Banys, MD – Personal Communication

33. Nicotine Replacement Dosing? 80% of 1-PPD smokers not adequately replaced with 21mg nicotine patch Clear Dose-Response Curve 1 Serum Cotinine 24-Hour half-life of nicotine metabolism Dose to level No absolute maximum 10-15% smoke free at one year 1. Sachs DPL. J Smoking-Related Dis 1994;5: 183-193

34. Bupropion (Wellbutrin/Zyban) Mechanism Affects dopaminergic projections Dosing Start 1 week before quit date 150mg SR x 3-6 days then 150mg BID Psychosocial treatment recommended Contraindications Seizure Disorder Eating Disorder

36. Bupropion (Wellbutrin/Zyban) Common SE Insomnia – 28-35% vs. 22%* Headache – 30% vs. 28% Dry Mouth – 15% vs. 5%* Dizziness – 8-9% vs. 8% Nausea – 5-7% vs. 5% Uncommon SE Seizures (1/1000 patients) Psychosis Hypertension Suicidal Ideation * Statistically significant

37. Varenicline (Chantix) Mechanism Α4β2 - Nicotinic Receptor Partial Agonist Dosing 0.5mg PO qd x 3 days 0.5mg PO BID x 4 days 1mg BID thereafter Quit date is day #8

38. Varenicline (Chantix) Duration 3 months initial 6 months total (if pt. can get 10 days smoke-free in first 3 months

39. Varenicline Warnings Common SE: Nausea Abnormal Sleep / Dreams Dizziness Fatigue Uncommon AE but reported: Aggressive and erratic behavior Suicidal thoughts Possible suicide attempts

40. Varenicline vs. Bupropion Weeks 9-52 Abstinence

41. Varenicline Maintenance

42. Conclusions & Recommendations 1. Tobacco Use is the #1 preventable cause of death 2. Psychiatric Patients carry a large disease burden both medical and physical 3. Tobacco is the problem - NOT Nicotine 4. Tobacco Use Disorder is a Chronic Illness needing repeated intervention 5. Smoking Cessation Works 6. Combine your treatments