Mental Health and Smoking Cessation

1. Mental Health and Smoking Cessation Steven A. Schroeder, M.D., Director Smoking Cessation Leadership Center National Association of Psychiatric Health Systems July 26, 2007

2. The Smoking Cessation Leadership Center Began in 2003 as a Robert Wood Johnson National Program Office with a $10-million, five-year grant Aimed at helping clinicians do a better job intervening with tobacco users Additional funding from VA, American Legacy Foundation New foray into behavioral health arena, from Legacy grant

3. SCLC’s Aim We want more people who want to quit smoking to get the help and support they need to succeed Access to cessation tools and resources needs to be widened for all groups Health care providers have a special role, as the many partners we have already enlisted will attest Examples: dental hygienists, nurses, physicians, respiratory therapists, physician assistants, pharmacists

4. Tobacco’s Deadly Toll 435,000 deaths in the U.S. each year 4.8 million deaths world wide each year 10 million deaths estimated by year 2030 8.6 million disabled from tobacco in the U.S. alone

6. Cigarette smoking is the primary known preventable cause of premature death in the U.S. Each year, nearly half a million Americans die from cigarette smoking; one of every five deaths in the U.S. is smoking related (CDC, 1999). This number surpasses the combined death toll due to alcohol, car accidents, suicides, homicides, HIV disease, and illicit drug use. Average number of years of life lost because of smoking, for male and female smokers (CDC, 2002): Males 13.2 years Females 14.5 years A total of 437,902 annual deaths due to cigarette smoking are reported by the CDC (2005) as follows: Cardiovascular disease………… 137,979 Hypertension, ischemic heart disease, other heart diseases, cerebrovascular diseases, atherosclerosis, aortic aneurysm, other arterial disease Lung cancer………………………123,836 Trachea, lung, bronchus Respiratory diseases…………….101,454 Pneumonia, influenza, bronchitis, emphysema, chronic airway obstruction Second-hand smoke……………....38,112 Cancers other than lung…………..34,693 Lip, oral cavity, pharynx, esophagus, pancreas, larynx, cervix, uterus, urinary bladder, kidney, other urinary Other………………………………….1,828 Note that the NCI monograph Health Effects of Exposure to Environmental Tobacco Smoke (National Cancer Institute, 1999) estimates that 53,000 lives are lost annually due to second-hand smoke. Centers for Disease Control and Prevention. Annual smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 1997–2001. MMWR 2005;54:625–628. National Cancer Institute. Health Effects of Exposure to Environmental Tobacco Smoke: The Report of the California Environmental Protection Agency. Smoking and Tobacco Control Monograph No. 10. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Publication No. 99-4645, 1999, pp. 185–264.Cigarette smoking is the primary known preventable cause of premature death in the U.S. Each year, nearly half a million Americans die from cigarette smoking; one of every five deaths in the U.S. is smoking related (CDC, 1999). This number surpasses the combined death toll due to alcohol, car accidents, suicides, homicides, HIV disease, and illicit drug use. Average number of years of life lost because of smoking, for male and female smokers (CDC, 2002): Males 13.2 years Females 14.5 years A total of 437,902 annual deaths due to cigarette smoking are reported by the CDC (2005) as follows: Cardiovascular disease………… 137,979 Hypertension, ischemic heart disease, other heart diseases, cerebrovascular diseases, atherosclerosis, aortic aneurysm, other arterial disease Lung cancer………………………123,836 Trachea, lung, bronchus Respiratory diseases…………….101,454 Pneumonia, influenza, bronchitis, emphysema, chronic airway obstruction Second-hand smoke……………....38,112 Cancers other than lung…………..34,693 Lip, oral cavity, pharynx, esophagus, pancreas, larynx, cervix, uterus, urinary bladder, kidney, other urinary Other………………………………….1,828 Note that the NCI monograph Health Effects of Exposure to Environmental Tobacco Smoke (National Cancer Institute, 1999) estimates that 53,000 lives are lost annually due to second-hand smoke. Centers for Disease Control and Prevention. Annual smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 1997–2001. MMWR 2005;54:625–628. National Cancer Institute. Health Effects of Exposure to Environmental Tobacco Smoke: The Report of the California Environmental Protection Agency. Smoking and Tobacco Control Monograph No. 10. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Publication No. 99-4645, 1999, pp. 185–264.

7. Health Consequences of Smoking Cancers Lung Laryngeal, pharyngeal, oral cavity, esophagus Pancreatic Bladder and kidney Cervical and endometrial Gastric Acute myeloid leukemia Reduce fertility in women, poor pregnancy outcomes, low birth weight babies, sudden infant death syndrome Cardiovascular diseases Sub clinical atherosclerosis Coronary heart disease Stroke Abdominal aortic aneurysm Respiratory diseases Acute respiratory illnesses, e.g., pneumonia Chronic respiratory diseases, e.g., COPD Cataract Periodontitis The 2004 Surgeon General’s Report on the health consequences of smoking describes a long list of diseases with sufficient evidence to infer a causal relationship with smoking. ? Note to instructor(s): For more detailed information and literature citations regarding risks for these tobacco-related illnesses, refer to the Pathophysiology of Tobacco-Related Disease module or the Surgeon General’s Report at http://www.surgeongeneral.gov/library/smokingconsequences. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Available at http://www.surgeongeneral.gov/library/smokingconsequences. Accessed May 29, 2004.The 2004 Surgeon General’s Report on the health consequences of smoking describes a long list of diseases with sufficient evidence to infer a causal relationship with smoking. ? Note to instructor(s): For more detailed information and literature citations regarding risks for these tobacco-related illnesses, refer to the Pathophysiology of Tobacco-Related Disease module or the Surgeon General’s Report at http://www.surgeongeneral.gov/library/smokingconsequences. U.S. Department of Health and Human Services. The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Available at http://www.surgeongeneral.gov/library/smokingconsequences. Accessed May 29, 2004.

8. The Real Culprit It is the smoke, tar, and additives that make people sicken and die. The nicotine is dangerous because it addicts people to tobacco. Staff and patients in settings that allow smoking are being exposed continually to lethal substances.

9. Causal Associations of Second Hand Smoke Developmental Low birth weight Sudden infant death Pre-term delivery Carcinogenic Lung cancer Nasal sinus cancer Breast cancer (younger, premenopausal women) Respiratory Asthma induction and exacerbation Eye and nasal irritation Bronchitis, pneumonia, otitis media in children Cardiovascular Heart disease mortality Acute and chronic coronary heart disease morbidity Altered vascular properties

10. Reducing Exposure Dangers of secondhand smoke are leading to tightening of smoke-free rules and laws JCAHO has moved to requiring smoke-free hospitals Both in-patient and out-patient settings needs to be conducive to quitting Both consumers and providers need support Psychiatric facilities need to make cessation services available to those who wish to quit

11. Compounds in Tobacco Smoke Tobacco smoke, which is inhaled either directly or as second-hand smoke, contains an estimated 4,800 compounds. The majority of the compounds are present in the particulate phase, suspended in tobacco smoke. Based on a classification system by the International Agency for Research on Cancer, there currently are 11 known human carcinogens (Group I), 7 probable human carcinogens (Group 2A), and 49 animal carcinogens that possibly also are carcinogens in humans (Group 2B) (NCI, 2001). Examples of detrimental compounds (some of which are carcinogens) in tobacco smoke include the following: Carbon monoxide: automobile exhaust; binds to hemoglobin, inhibits respiration Hydrogen cyanide: gas chamber poison; highly ciliotoxic, inhibits lung clearance Ammonia: floor/toilet cleaning agent; irritation of respiratory tract Nicotine : addictive substance; toxic alkaloid Benzene: solvent, banned substance in organic chemistry labs; Group I carcinogen Nitrosamines: carcinogenic in animals and probably in humans; Group 2A and 2B carcinogens Lead: heavy metal, toxic to central nervous system; Group 2B carcinogen Cadmium: heavy metal found in rechargeable batteries; Group I carcinogen Hexavalent chromium: highlighted in the movie Erin Brockovich; Group I carcinogen Arsenic: pesticide; Group I carcinogen Polonium-210: radioactive agent; Group I carcinogen Formaldehyde: embalming fluid; Group 2B carcinogen Other substances in tobacco smoke (not listed above) that have sufficient evidence to be classified as Group I carcinogens in humans include 2-naphthylamine, 4-aminobiphenyl, vinyl chloride, ethylene oxide, beryllium, nickel, and cadmium. National Cancer Institute. Risks Associated with Low Machine-Measured Yields of Tar and Nicotine. Smoking and Tobacco Control Monograph No. 13. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Publication No. 02-5074, October 2001.Tobacco smoke, which is inhaled either directly or as second-hand smoke, contains an estimated 4,800 compounds. The majority of the compounds are present in the particulate phase, suspended in tobacco smoke. Based on a classification system by the International Agency for Research on Cancer, there currently are 11 known human carcinogens (Group I), 7 probable human carcinogens (Group 2A), and 49 animal carcinogens that possibly also are carcinogens in humans (Group 2B) (NCI, 2001). Examples of detrimental compounds (some of which are carcinogens) in tobacco smoke include the following: Carbon monoxide: automobile exhaust; binds to hemoglobin, inhibits respiration Hydrogen cyanide: gas chamber poison; highly ciliotoxic, inhibits lung clearance Ammonia: floor/toilet cleaning agent; irritation of respiratory tract Nicotine : addictive substance; toxic alkaloid Benzene: solvent, banned substance in organic chemistry labs; Group I carcinogen Nitrosamines: carcinogenic in animals and probably in humans; Group 2A and 2B carcinogens Lead: heavy metal, toxic to central nervous system; Group 2B carcinogen Cadmium: heavy metal found in rechargeable batteries; Group I carcinogen Hexavalent chromium: highlighted in the movie Erin Brockovich; Group I carcinogen Arsenic: pesticide; Group I carcinogen Polonium-210: radioactive agent; Group I carcinogen Formaldehyde: embalming fluid; Group 2B carcinogen Other substances in tobacco smoke (not listed above) that have sufficient evidence to be classified as Group I carcinogens in humans include 2-naphthylamine, 4-aminobiphenyl, vinyl chloride, ethylene oxide, beryllium, nickel, and cadmium. National Cancer Institute. Risks Associated with Low Machine-Measured Yields of Tar and Nicotine. Smoking and Tobacco Control Monograph No. 13. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, NIH Publication No. 02-5074, October 2001.

12. Nicotine Distribution Inhalation of tobacco smoke is an effective means of delivering nicotine to the central nervous system. After inhalation, nicotine is rapidly absorbed across pulmonary epithelium into the arterial circulation, traveling via the carotid arteries to the central nervous system. Nicotine readily penetrates the blood-brain barrier, resulting in transient exposure of the brain to high levels of nicotine. Nicotine has been estimated to reach the brain within 11 seconds of inhalation. Following systemic distribution, brain nicotine levels decline rapidly (Benowitz, 1990). This graph depicts the arterial and venous concentrations of nicotine achieved during cigarette smoking. Within one minute after smoking a cigarette, arterial levels of nicotine are nearly seven times the corresponding venous levels (Henningfield et al., 1993). These rapid, high levels of nicotine in the central nervous system produce an almost immediate effect thereby reinforcing the behavioral act of smoking which further stimulates repeated administration. Benowitz NL. Clinical pharmacology of inhaled drugs of abuse: Implications in understanding nicotine dependence. In Chiang CN, Hawks RL (eds.): Research Findings on Smoking of Abused Substances, NIDA Research Monograph 99. Rockville, MD: 1990. Available at: http://www.drugabuse.gov/pdf/monographs/download99.html [Accessed February 14, 2003] Henningfield JE, Stapleton JM, Benowitz NL, Grayson RF, London ED. Higher levels of nicotine in arterial than in venous blood after cigarette smoking. Drug Alcohol Depend 1993;33:23-9.Inhalation of tobacco smoke is an effective means of delivering nicotine to the central nervous system. After inhalation, nicotine is rapidly absorbed across pulmonary epithelium into the arterial circulation, traveling via the carotid arteries to the central nervous system. Nicotine readily penetrates the blood-brain barrier, resulting in transient exposure of the brain to high levels of nicotine. Nicotine has been estimated to reach the brain within 11 seconds of inhalation. Following systemic distribution, brain nicotine levels decline rapidly (Benowitz, 1990). This graph depicts the arterial and venous concentrations of nicotine achieved during cigarette smoking. Within one minute after smoking a cigarette, arterial levels of nicotine are nearly seven times the corresponding venous levels (Henningfield et al., 1993). These rapid, high levels of nicotine in the central nervous system produce an almost immediate effect thereby reinforcing the behavioral act of smoking which further stimulates repeated administration. Benowitz NL. Clinical pharmacology of inhaled drugs of abuse: Implications in understanding nicotine dependence. In Chiang CN, Hawks RL (eds.): Research Findings on Smoking of Abused Substances, NIDA Research Monograph 99. Rockville, MD: 1990. Available at: http://www.drugabuse.gov/pdf/monographs/download99.html [Accessed February 14, 2003] Henningfield JE, Stapleton JM, Benowitz NL, Grayson RF, London ED. Higher levels of nicotine in arterial than in venous blood after cigarette smoking. Drug Alcohol Depend 1993;33:23-9.

13. Drugs such as cocaine, heroin, amphetamine, and nicotine exert profound effects on the brain. These agents have in common the ability to stimulate the release of the neurotransmitter dopamine in the midbrain. Dopamine induces feelings of euphoria and pleasure and is responsible for activating the dopamine reward pathway (Leshner, 1997). The dopamine reward pathway, as depicted in this simplified diagram, is a network of nervous tissue in the middle of the brain that elicits feelings of pleasure in response to certain stimuli. The important interconnected structures of the reward pathway include the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex (area of the brain responsible for thinking and judgment). The neurons of the VTA contain the neurotransmitter dopamine, which is released in the nucleus accumbens and in the prefrontal cortex. Behaviors that naturally stimulate the reward pathway include eating to relieve hunger, drinking to alleviate thirst, or engaging in sexual activity. On a primitive, neurochemical level, stimulation of the reward pathway reinforces the behavior so that it will be repeated. Obviously these behaviors are necessary for continued survival of the organism. The reward pathway can also be stimulated by drugs of abuse such as cocaine, opiates, amphetamine, and nicotine. When these unnatural stimuli trigger the reward pathway the same pleasurable feelings are elicited. Researchers believe that, with chronic drug use, the brain becomes chemically altered—transforming a drug user into a drug addict (Leshner, 1997). Consider cigarette smoking as an example. Immediately following inhalation, a bolus of nicotine enters the brain, stimulating the release of dopamine, which induces nearly immediate feelings of pleasure and relief of symptoms of nicotine withdrawal. This rapid dose-response reinforces and perpetuates the smoking behavior. This slide is made available to the public through the National Institute on Drug Abuse Web page, at http://www.nida.nih.gov/Teaching/largegifs/slide-9.gif. Adapted with permission by Dr. Rochelle D. Schwartz-Bloom, Duke University. Leshner Al. Drug abuse and addiction are biomedical problems. Hosp Pract (special report) April 1997:2–4. Drugs such as cocaine, heroin, amphetamine, and nicotine exert profound effects on the brain. These agents have in common the ability to stimulate the release of the neurotransmitter dopamine in the midbrain. Dopamine induces feelings of euphoria and pleasure and is responsible for activating the dopamine reward pathway (Leshner, 1997). The dopamine reward pathway, as depicted in this simplified diagram, is a network of nervous tissue in the middle of the brain that elicits feelings of pleasure in response to certain stimuli. The important interconnected structures of the reward pathway include the ventral tegmental area (VTA), the nucleus accumbens, and the prefrontal cortex (area of the brain responsible for thinking and judgment). The neurons of the VTA contain the neurotransmitter dopamine, which is released in the nucleus accumbens and in the prefrontal cortex. Behaviors that naturally stimulate the reward pathway include eating to relieve hunger, drinking to alleviate thirst, or engaging in sexual activity. On a primitive, neurochemical level, stimulation of the reward pathway reinforces the behavior so that it will be repeated. Obviously these behaviors are necessary for continued survival of the organism. The reward pathway can also be stimulated by drugs of abuse such as cocaine, opiates, amphetamine, and nicotine. When these unnatural stimuli trigger the reward pathway the same pleasurable feelings are elicited. Researchers believe that, with chronic drug use, the brain becomes chemically altered—transforming a drug user into a drug addict (Leshner, 1997). Consider cigarette smoking as an example. Immediately following inhalation, a bolus of nicotine enters the brain, stimulating the release of dopamine, which induces nearly immediate feelings of pleasure and relief of symptoms of nicotine withdrawal. This rapid dose-response reinforces and perpetuates the smoking behavior. This slide is made available to the public through the National Institute on Drug Abuse Web page, at http://www.nida.nih.gov/Teaching/largegifs/slide-9.gif. Adapted with permission by Dr. Rochelle D. Schwartz-Bloom, Duke University. Leshner Al. Drug abuse and addiction are biomedical problems. Hosp Pract (special report) April 1997:2–4.

14. Chronic Administration of Nicotine: Effects on the Brain Chronic administration of nicotine results in an increased number of nicotine receptors in specific regions of the brain (Perry et al., 1999). This upregulation of nicotine receptors leads to the development of tolerance. Tolerance is a phenomenon by which repeated doses of a drug produce less of an effect than did the initial exposure. Perry DC, Davila-Garcia MI, Stockmeier CA, Kellar KJ. Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies. J Pharmacol Exp Ther 1999;289:1545–1552.Chronic administration of nicotine results in an increased number of nicotine receptors in specific regions of the brain (Perry et al., 1999). This upregulation of nicotine receptors leads to the development of tolerance. Tolerance is a phenomenon by which repeated doses of a drug produce less of an effect than did the initial exposure. Perry DC, Davila-Garcia MI, Stockmeier CA, Kellar KJ. Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies. J Pharmacol Exp Ther 1999;289:1545–1552.

15. Long Term (?6 month) Quit Rates for Available Cessation Medications Few head-to-head trials have compared the various tobacco cessation therapies. In a randomized controlled trial comparing the four NRT formulations available at the time, the products performed similarly, but patient compliance was higher with the patch, followed by the gum, which was higher than the inhaler and nasal spray (Hajek et al., 1999). This bar chart summarizes the long-term (?6-month) quit rates observed with the different NRT products, bupropion SR and varenicline (Gonzales et al., 2006; Hughes et al., 2004; Jorenby et al., 2006; Silagy et al., 2004). These data derive from 124 different placebo-controlled trials; therefore, it is inappropriate to compare the active medications with respect to clinical efficacy. What this chart does illustrate, however, is that the quit rates from each of the methods is approximately twice that of its corresponding placebo control treatment arm. Each of the pharmacotherapy options depicted in the chart is considered effective. When patients ask for assistance with their quit attempt, any product can be recommended, if not contraindicated. However, when assisting patients in choosing a product, clinicians should consider additional factors. The number of cigarettes smoked per day (or time to first cigarette, for the nicotine lozenge), level of dependence, advantages and disadvantages of each product, methods used for prior quit attempts and reasons for relapse, and the patient’s own product preference need to be considered. Behavioral counseling should be used in conjunction with all pharmacologic therapies. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. (1999). Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 159:2033–2038. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD000031. Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA 296:56-63. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD000146.Few head-to-head trials have compared the various tobacco cessation therapies. In a randomized controlled trial comparing the four NRT formulations available at the time, the products performed similarly, but patient compliance was higher with the patch, followed by the gum, which was higher than the inhaler and nasal spray (Hajek et al., 1999). This bar chart summarizes the long-term (?6-month) quit rates observed with the different NRT products, bupropion SR and varenicline (Gonzales et al., 2006; Hughes et al., 2004; Jorenby et al., 2006; Silagy et al., 2004). These data derive from 124 different placebo-controlled trials; therefore, it is inappropriate to compare the active medications with respect to clinical efficacy. What this chart does illustrate, however, is that the quit rates from each of the methods is approximately twice that of its corresponding placebo control treatment arm. Each of the pharmacotherapy options depicted in the chart is considered effective. When patients ask for assistance with their quit attempt, any product can be recommended, if not contraindicated. However, when assisting patients in choosing a product, clinicians should consider additional factors. The number of cigarettes smoked per day (or time to first cigarette, for the nicotine lozenge), level of dependence, advantages and disadvantages of each product, methods used for prior quit attempts and reasons for relapse, and the patient’s own product preference need to be considered. Behavioral counseling should be used in conjunction with all pharmacologic therapies. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hajek P, West R, Foulds J, Nilsson F, Burrows S, Meadow A. (1999). Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 159:2033–2038. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD000031. Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA 296:56-63. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. (2004). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 3:CD000146.

16. Trends in Adult Smoking, by Sex—U.S., 1955–2004 This graph demonstrates trends in smoking among adults in the U.S. between 1955 and 2004 (CDC, 1999, 2005). Since 1990, the smoking prevalence among men and women has experienced only a slight decline, compared to previous decades, highlighting a need for enhanced tobacco control efforts. In 2004, results of the National Health Interview Survey (NHIS) indicated that approximately 44.5 million adults (20.9% of the U.S. adult population) are current smokers1 (CDC, 2005). Of these, 81.3% smoke every day and 18.7% smoke some days (CDC, 2005). More men (23.4%) than women (18.5%) are current smokers. An estimated 70% of all smokers want to quit completely (CDC, 2002). In 2004, approximately 14.6 million (40.5%) of 36.1 million every-day, current smokers stopped smoking at least 1 day during the past 12 months because they were trying to quit (CDC, 2005). In 2004, an estimated 45.6 million adults were former smokers,2 representing 50.6% of persons who had ever smoked (CDC, 2005). ? Note to instructor(s): Cessation statistics vary depending on factors such as the duration of follow-up, definitions of abstinence, and whether reports of cessation were biologically confirmed. According to the CDC (2002), 4.7% of smokers who had smoked every day or some days during the past year had quit and were able to maintain abstinence for 3–12 months in 2000. 1Current smokers: persons who reported having smoked 100 or more cigarettes during their lifetime and who smoked every day or some days at the time of the interview. 2Former smokers: persons who reported having smoked 100 or more cigarettes during their lifetime but currently did not smoke. Centers for Disease Control and Prevention (CDC). (1999). Achievements in public health, 1900–1999: Tobacco use—United States, 1900–1999. MMWR 48:986–993. Centers for Disease Control and Prevention. (2002). Cigarette smoking among adults—United States, 2000. MMWR 51:642–645. Centers for Disease Control and Prevention. (2005). Cigarette smoking among adults—United States, 2004. MMWR 54:1121–1124.This graph demonstrates trends in smoking among adults in the U.S. between 1955 and 2004 (CDC, 1999, 2005). Since 1990, the smoking prevalence among men and women has experienced only a slight decline, compared to previous decades, highlighting a need for enhanced tobacco control efforts. In 2004, results of the National Health Interview Survey (NHIS) indicated that approximately 44.5 million adults (20.9% of the U.S. adult population) are current smokers1 (CDC, 2005). Of these, 81.3% smoke every day and 18.7% smoke some days (CDC, 2005). More men (23.4%) than women (18.5%) are current smokers. An estimated 70% of all smokers want to quit completely (CDC, 2002). In 2004, approximately 14.6 million (40.5%) of 36.1 million every-day, current smokers stopped smoking at least 1 day during the past 12 months because they were trying to quit (CDC, 2005). In 2004, an estimated 45.6 million adults were former smokers,2 representing 50.6% of persons who had ever smoked (CDC, 2005). ? Note to instructor(s): Cessation statistics vary depending on factors such as the duration of follow-up, definitions of abstinence, and whether reports of cessation were biologically confirmed. According to the CDC (2002), 4.7% of smokers who had smoked every day or some days during the past year had quit and were able to maintain abstinence for 3–12 months in 2000. 1Current smokers: persons who reported having smoked 100 or more cigarettes during their lifetime and who smoked every day or some days at the time of the interview. 2Former smokers: persons who reported having smoked 100 or more cigarettes during their lifetime but currently did not smoke. Centers for Disease Control and Prevention (CDC). (1999). Achievements in public health, 1900–1999: Tobacco use—United States, 1900–1999. MMWR 48:986–993. Centers for Disease Control and Prevention. (2002). Cigarette smoking among adults—United States, 2000. MMWR 51:642–645. Centers for Disease Control and Prevention. (2005). Cigarette smoking among adults—United States, 2004. MMWR 54:1121–1124.

17. Smoking Prevalence Among Those with Mental Illness Prevalence is 75 percent for those with either addictions and/or mental illness, as opposed to 20.6 percent for the general population In mental health settings, about 30-35 percent of the staff smoke

18. People with mental illness consume 45% of cigarettes smoked in U.S.Breslau, 2003

19. The Extraordinary Toll* People with serious mental illness die 25 years earlier than the general population Most attributed to smoking, obesity, substance abuse, and inadequate access to medical care * R. Manderscheid and C. Colton, April 2006, in Preventing Chronic Disease

20. Association of Smoking and Psychiatric Disorders Rates among specific diagnoses General population 20.9% Panic disorder 35% Depression 49% Alcohol dependence 80% Schizophrenia/Bipolar Disorder 88% Hughes, 1986

21. Smoking Rates Compared to the Number of Lifetime Psychiatric Diagnoses

22. Additional Complications of Smoking and Psychiatric Disorders Additive mortality risks Heart disease is 7X higher than peers and more than 7x the suicide rate. Department of Mental Health, Massachusetts, 2001 Affects psychotropic blood levels Depressed smokers have higher suicide rates than depressed nonsmokers Bruce, 1994 Lohr, 1992 Yassa, 1987

23. Fundamental Problems: Smokers with Psychiatric Disorders Neurobiological factors reinforce use of nicotine Feel excluded from mainstream cessation programs Lower rate of quit attempts Higher tobacco relapse rates

24. Fundamental Problems: Smokers with Psychiatric Disorders(2) Long considered part of psychiatric culture Clinicians believe they are not able/willing to quit For those with chronic psychiatric disorders Major part of daily routine/structure Alleviates stigma Positive/negative freedoms

25. Tobacco Use and Specific Psychiatric Disorders Major Depression (MDD) Anxiety Disorders Alcohol abuse/dependence Schizophrenia/Bipolar Disorder

26. Link Between MDD and Smoking

27. Smoking and MDD Smokers with a past history of MDD More likely to have post-cessation MDD Risk greatest first 6 months post-cessation Leads to more severe nicotine withdrawal symptoms High risk for relapse in first week Female risk>male Quattorocki, 2000 Niaura, 1999 Hughes 2007

28. Treatment Options for Smokers Counseling Pharmacotherapy

29. Pharmacologic Methods: First-line Therapies Three general classes of FDA-approved drugs for smoking cessation: Nicotine replacement therapy (NRT) Nicotine gum, patch, lozenge, nasal spray, inhaler Psychotropics Sustained-release bupropion Partial nicotinic receptor agonist Varenicline There are three general classes of FDA-approved drugs for cessation: Nicotine replacement therapy (NRT) includes the nicotine gum, patch, lozenge, nasal spray, and inhaler. A nicotine sublingual tablet currently is available in Europe. The only psychotropic agent currently approved by the FDA for smoking cessation is bupropion SR. Varenicline, a partial nicotinic receptor agonist, was approved by the FDA in 2006 for smoking cessation. According to the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence, NRT and sustained-release bupropion are considered first-line pharmacotherapies for smoking cessation (Fiore et al., 2000). Varenicline, which was approved six years after the Guideline was published, is not formally classified as a first-line agent although controlled trials suggest it is equal to (Gonzales et al., 2006) or superior to (Jorenby et al., 2006) sustained-release bupropion. Currently, no medications have an FDA indication for use in spit tobacco cessation. ? Note to instructor(s): The following pharmacotherapies have been studied but are not recommended by the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000): Anxiolytic agents (buspirone, diazepam) may reduce anxiety associated with nicotine withdrawal, but these agents have not been shown to improve quit rates. Mecamylamine (Inversine) is a central/peripheral nicotinic receptor antagonist. The rationale for its use is that the blockade of the nicotine receptors will prevent the positive reinforcing and pleasurable effects of smoking. Evidence for its use as a smoking cessation aid alone is insufficient. Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline), which may be used to treat withdrawal-associated depression, were not found to be effective in a meta-analysis of five trials (Hughes et al., 2004). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD000031. Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA 296:56-63. Slide is used with permission, Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright © 1999-2007 The Regents of the University of California, University of Southern California, and Western University of Health Sciences. All rights reserved.There are three general classes of FDA-approved drugs for cessation: Nicotine replacement therapy (NRT) includes the nicotine gum, patch, lozenge, nasal spray, and inhaler. A nicotine sublingual tablet currently is available in Europe. The only psychotropic agent currently approved by the FDA for smoking cessation is bupropion SR. Varenicline, a partial nicotinic receptor agonist, was approved by the FDA in 2006 for smoking cessation. According to the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence, NRT and sustained-release bupropion are considered first-line pharmacotherapies for smoking cessation (Fiore et al., 2000). Varenicline, which was approved six years after the Guideline was published, is not formally classified as a first-line agent although controlled trials suggest it is equal to (Gonzales et al., 2006) or superior to (Jorenby et al., 2006) sustained-release bupropion. Currently, no medications have an FDA indication for use in spit tobacco cessation. ? Note to instructor(s): The following pharmacotherapies have been studied but are not recommended by the U.S. Public Health Service Clinical Practice Guideline for treating tobacco use and dependence (Fiore et al., 2000): Anxiolytic agents (buspirone, diazepam) may reduce anxiety associated with nicotine withdrawal, but these agents have not been shown to improve quit rates. Mecamylamine (Inversine) is a central/peripheral nicotinic receptor antagonist. The rationale for its use is that the blockade of the nicotine receptors will prevent the positive reinforcing and pleasurable effects of smoking. Evidence for its use as a smoking cessation aid alone is insufficient. Selective serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline), which may be used to treat withdrawal-associated depression, were not found to be effective in a meta-analysis of five trials (Hughes et al., 2004). Fiore MC, Bailey WC, Cohen SJ, et al. (2000). Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. Gonzales D, Rennard SI, Nides M, et al. (2006). Varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47-55. Hughes JR, Stead LF, Lancaster. (2004). Antidepressants for smoking cessation. Cochrane Database Syst Rev 4:CD000031. Jorenby DE, Hays JT, Rigotti NA, et al. (2006). Efficacy of varenicline, an ?4ß2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA 296:56-63. Slide is used with permission, Rx for Change: Clinician-Assisted Tobacco Cessation. Copyright © 1999-2007 The Regents of the University of California, University of Southern California, and Western University of Health Sciences. All rights reserved.

30. NRT and MDD NRT alone insufficient treatment for smokers with current/past MDD No effect on mood Cessation rates not improved Thorsteinsson, 2001 Smith, 2003

31. SSRI’s and Smokers with MDD No benefit for smoking cessation Can offset negative moods during a quit attempt Can reduce likelihood of emergent depression during quit attempt Can be combined with Bupropion/NRT Can be combined with varenicline Cook, 2004 Chengappa, 2001 Smith, 2003

32. Bupropion and Smokers with MDD Can be used as monotherapy for both problems Can be combined with varenicline, though no FDA approval yet Treatment may need to be extended beyond traditional 3-6 months

33. Combined Treatments for Depressed Smokers Adding Cognitive Behavioral Therapy to standard treatments show mixed results No research available for other types of non-pharmacological interventions Brown, 2007 Hall, 2006

34. Smoking and Anxiety Disorders Smokers have greater anxiety and panic symptoms than non-smokers Heavy smoking in adolescence associated with higher risk of developing Agoraphobia GAD Panic disorder Increased risk for relapse during early stages of quit attempt Breslau, 2004 Amering, 1999

35. SSRI’s and Smokers with Anxiety Disorders No benefit for smoking cessation Can reduce likelihood of emergent anxiety or panic during quit attempt Bupropion not appropriate as only medication Carefully combined with Bupropion/NRT Can be combined with varenicline

36. Smoking Cessation and PTSD Cessation not associated with worsening of PTSD symptoms Integration into standard care improves quit rates Bupropion tolerated and effective treatment McFall, 2006 Hertzberg, 2001

37. Smoking and Alcohol Dependence Over 72% of alcoholics are heavy smokers (9% of general pop.) Increased urge to drink among alcoholic smokers when they smell cigarettes Dawson, 2000

38. Cessation Treatment for Alcohol Users Standard cessation treatments are effective No evidence of increased use of other substances during cessation treatment Alcohol abstinence days greatest for those who quit smoking Saxon, 2003 Kohn, 2003

39. Smoking and Schizophrenia/Bipolar Disorder Highest smoking rates than any other patient group Smoke 10 billion packs per year More per day Prefer high tar, high nicotine Smoke to ends of cigarettes D’Mello, 2001

40. Smoking Cessation for Schizophrenia/Bipolar Disorder Have lower cessation rates than general population Cognitive deficits may contribute to cessation treatment failure Traditional cessation treatments may be inadequate Harm reduction and NRT Hospitalization may be unique opportunities to initiate treatment

41. Bupropion for Smoking Cessation in Schizophrenia Can lead to smoking reduction Quit rates comparable to general population and durable Quit rates enhanced with CBT Overall symptoms not worsened Evins, 2004, 2005 Fatemi, 2005 George, 2002

42. Mental Disorders and Quit Rates Quit rates among those with current M.H. diagnosis are significantly lower than for those with no history of mental illness Quit rates among smokers with a history of alcohol and substance abuse and social phobias are significantly lower than for those without this history

43. Mental Disorders and Quit Rates (2) Quit rates among smokers with a past history of major depression and simple phobias are similar to smokers without this history

44. Smoking Complicates Dosing of Psychotropic Medications Smoking can increase medication metabolism, so higher doses are needed when smoking. When smokers quit, reductions in the metabolism of meds could result in relatively greater dose levels over time, with greater potential for adverse effects.

45. Key Factors in Treatment of Smokers with Mental Illness Timing– there is concern, but no clear guidelines, about when treatment should be introduced during periods of acute psychiatric stress. Increasing evidence that nicotine dependence treatment does not hurt recovery and may improve outcomes.

46. Behavioral Interventions Motivate these smokers to stop and teach basic cessation skills. Protocols exist for patients seen in mental hospital settings. These rely on prior knowledge of smoker’s diagnosis, medication, history, and training to monitor symptoms and adjust medications.

47. Behavioral Interventions (2) Protocols for smokers with history of mental illness seeking tobacco dependence treatment outside mental health facilities and clinics should follow standard treatment guidelines Need to adjust these protocols to account for their special circumstances

48. Resistance to Cessation for People with Mental Illnesses Many loved ones of persons with mental illness resist helping them quit They feel protective and want to focus on quality, not quantity, of life But diseases caused by smoking can severely hamper quality as well as quantity of life And second-hand smoke imperils loved ones and workers

49. Barriers to Successful Cessation Provider inattention/pessimism Co-dependency and mental illness Mental health staff smoke Historic attitudes about smoking in mental health community No coverage for cessation drugs Improper use of the drugs Ignorance of quitlines

50. Necessary Mental Health Care System Interventions Systematic identification processes that mesh with a non-medical practice style Educational efforts for providers that emphasize the detrimental effects of smoking on mental health Integration of cessation efforts with primary mental health treatments Address emotional/behavioral comorbidity that effect cessation efforts in primary care settings Smoke free facilities to protect patients, their families, and staff

51. Smoke Free Facilities as Key Element NASMHPD project to make all public facilities smoke-free (hospital and campus) --43% smoke-free at 2005 -->50% smoke free now --new smoke free hospitals one/month What are the numbers for private hospitals?

52. Mental Health Benefits From Treating Tobacco Dependence Emerging evidence that morbidity is reduced May enhance abstinence from substances Reduced financial burden Increased self-confidence Increasing focus on mental health and wellness

53. Power of Intervention ? to ½ of the 44.5 million smokers will die from the habit. Of the 31 million who want to quit, 10 to 15.5 million will die from smoking. Increasing the 2.5% cessation rate to 10% would save 1.2 million additional lives. If cessation rates rose to 15%, 1.9 million additional lives would be saved. No other health intervention could make such a difference!

54. Thank Youhttp://smokingcessationleadership.ucsf.edu Special thanks to Eric Heiligenstein, M.D. Clinical Director, Psychiatry Service University Health Services Associate, CTRI University of Wisconsin-Madison