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Harvard Alumni Day Address June 2006 Dr Kinnunen
- 1. Tobacco Dependence and Its Treatment Taru Hannele Kinnunen, PhD Harvard Medical School Harvard School Dental Medicine Department of Oral Health Policy and Epidemiology Harvard Medical School Alumni Day Plenary June 2006
- 6. Tobacco Use and Oral Cavity TOBACCO USE Pre- cancerous Lesions Oral Cancers Gingivitis Periodontitis Acute Ulcero-Necrotic Gingivitis Teeth colorations Halitosis Sense of taste/smell Chronic Sinusitis Consequences in implantology Consequences in wound healing
- 7. Tobacco Dependence a Chronic Syndrome ICD-10: 17 Mental and behavioral disorders due to use of tobacco 17.1 Harmful use 17.2 Dependence syndrome 17.3 Withdrawal state DSM-IV-TR: Nicotine Use Disorder 305.1 Nicotine Dependence 292.0 Nicotine Withdrawal Dental code D1320 Tobacco counseling for the control and provision of oral disease
- 8. Smoking in Perspective Kills more than 430,000 Americans each year 25% of adult Americans smoke 3,000 children and adolescents become regular tobacco users every day Causes cancer, heart disease, stroke, pulmonary disease, and adverse pregnancy outcomes Adds $50 billion in direct health costs each year One-third of all tobacco users in U.S. will die prematurely
- 9. Health Consequences of Smoking Cessation Smoking is number 1 preventable cause of death Treating tobacco dependence cost-effective significant measure in primary and secondary prevention Smoking cessation results in many positive health consequences most immediately and substantially coronary heart disease and other cardiovascular diseases (CVD) (USDHH. Women and smoking: A report of the Surgeon General 2001.), (Benowitz 2003, Kinnunen Mustonen 2004)
- 10. Treatment after CHD: Reduction of the Mortality Risk 39% 29% 23% 23% 15% 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% Smoking Cessation Statins Beta-blockers ACE-Inhibitors Aspirin JAMA, 2003 BMJ, 2000 BMJ, 1999 Lancet, 2000 BMJ, 2002
- 11. Difficulty in Quitting 70% of tobacco users would like to quit Less than 10% succeed in a given year Long term or permanent abstinence may be achieved after several attempts. Only 5-10% tobacco users are not nicotine dependent
- 12. Nicotine Dependence Copyright 息 2002, TK. All rights reserved. Physiological dependence neurobiology: neuromodulation and neuroadaptation genetics positive and negative reinforcment withdrawal Conditioning/Learning highly conditioned behavior 20 cigarettes x 10 puffs= 200 repetitions slips, relapse Sensory aspect of smoking
- 13. Clinical Guidelines for TX Intensity: Dose-response Type: Individual/Group Content Problem solving/Skills training Intra-treatment social support Extra-treatment social support First-line therapies: NRT (gum, patch, lozenge, inhlaler, spray) BupropionSR*(Zyban, Wellbutrin) Second-line therapies: nortriptyline clonidine Combination therapies NRT+NRT Bupropion SR + NRT New Therapies Varenicline (Chantix) Counseling Behavioral Tx Pharmacological Tx
- 14. 1-year Abstinence in Studies with NRT and Behavioral Counseling 0 20 40 60 80 100 %Abstinent 1-week 16-weeks 1-year Ex_NicGum CG_NicGum NicGum 0 10 20 30 40 50 60 70 80 90 100 1-week 16-week 1-year NicGum 1992-1995 1999-2002 (Garvey & Kinnunen, NIDA) (Kinnunen, NIDA)
- 15. From Tobacco Plant to Cigarettes
- 17. Acute Exposure of Nicotine Tobacco smoke contains concentrated amounts of nicotine Fast delivery to brain Stimulation and release of Ach Modulation of other neurotransmitters Neuromodulation
- 18. nicotine receptor nAChR nicotine molecules from tobacco smoke Acetylcholine ACh Synapse
- 20. Most Effects are Mediated by Nicotinic Receptors (nAChRs) Subtype 留4硫2 17 subtypes (留4硫2, 留7)
- 21. Minutes Increaseinnicotineconcentration (ng/ml) Cigarette Gum 4mg Gum/ Lozenge 2mg Inhaler Nasal spray Patch 5 10 15 20 25 30 0 2 4 6 8 10 12 14 Plasma Nicotine Concentrations for Smoking and NRT Source: Balfour DJ & Fagerstr旦m KO. Pharmacol Ther 1996 72:51-81.
- 22. Individualizing Treatment Double Blind Placebo Controlled Study Individualized Treatment 50% Nicotine Replacement 21 mg Nicotine Patch 42 mg Nicotine Patch 100% Nicotine Replacement Placebo Patch Garvey & Kinnunen 2001-2005 NIDA Does 100% replacement of nicotine using nicotine patches lead higher abstinence rates?
- 23. Potential Factors Impacting Cotinine Levels Obtained from Nicotine Patches Patch Dose Baseline Cotinine Level Level of Dependence on Nicotine Pack years (packs/day x no. of years smoked) Cigarettes per day smoked Age Sex Race Body Mass Index Clearance (Baseline cot./cigs per day) Type of cigarette (Menthol/ NonMenthol)
- 24. 0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375 Days Post - Cessat ion 0 10 20 30 40 50 60 70 80 90 100 PercentAbstinent Abstinence Patterns by Treatment Group 100% 50% 0 mg 21 mg 42 mg p = .05 Garvey et al., 2006
- 25. Improving Treatment Adjuncts to behavioral and pharmacological treatments may be one solution Tailoring treatments to specific population > WOMEN Women more fearful of gaining weight Women report more often negative affectivity and stress after quitting Depression and smoking cessation have a strong association and depression is more common among women
- 26. Aerobic Exercise and NRT for Female Smokers - Study DA12503-01_04 Kinnunen (1999-2003) sedentary smokers ages 18-55 no cardiac Hx over 5 cigarettes/day Equal Contact Group (n=56) Wellness Counseling (2 x week) 3 wks prequit 16 wks postquit Nicotine gum Brief Counseling Experimental Group (n=92) Aerobic Exercise (2-3 x week) 3 wks prequit 16 wks postquit Nicotine gum Brief Counseling Standard Care Control Group (n= 34) _ Nicotine gum Brief Counseling
- 27. 1-Year Smoking Abstinence Cumulative Proportion Surviving (Kaplan-Meier) Exercise and NRT Study 0 50 100 150 200 250 300 350 400 450 Time 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 CumulativeProportionSu Standard care Exercise Wellness Exercise and Wellness groups were significantly different (p<.05) from the Standard Care group Kinnunen et al, 2005, Noc Tobacco Res
- 28. Conclusions Exercise promoted smoking cessation beyond standard care Exercise had favorable impact on mood Poor adherence to exercise regimen among those who had: Higher nicotine dependence Higher body mass index Higher depression level Higher stress level Lower education Korhonen, Kinnunen et al., 2005, Tob Induced Dis
- 29. Increasing Adherence to TX Optimizing settings (home vs. facility) Reducing barriers Increasing adherence with counseling Continuing NRT Mapping out CVD risk profile better and assessing harm reduction NIDA DA12503
- 30. Future Directions Expanding and enhancing behavioral treatments (Front-loaded counseling Garvey & Kinnunen, NIDA) Discovering new and new combinations of pharmacotherapy Immunotherapy Nicotine vaccine Harm reduction
- 31. Nicotine Vaccine Nicotine vaccine is designed to elicit the production of nicotine antibodies. If someone smokes after being immunized, the antibodies bind with nicotine molecules in the bloodstream and prevent them from entering the brain where nicotine receptors are located. Previous research has shown that, since antibody levels rise slowly, smokers lose the nicotine reward gradually, avoiding withdrawal symptoms.
- 32. "Quitting smoking is easy. I've done it a thousand times. - Mark Twain