1. Treating Tobacco Dependence in Patients with Other Addictions Richard D. Hurt, M.D. Professor of Medicine, Mayo Clinic College of Medicine Director, Nicotine Dependence Center http://ndc.mayo.edu

2. Smoking and Mental Illness 22% of people who have never been diagnosed with a mental illness currently smoke. 22% of people who have never been diagnosed with a mental illness currently smoke. 34.8% of people who have had been diagnosed with a mental illness sometime in their life currently smoke. 34.8% of people who have had been diagnosed with a mental illness sometime in their life currently smoke. 41% of people who have been diagnosed with a mental illness In the past month currently smoke 41% of people who have been diagnosed with a mental illness In the past month currently smoke 44% of all cigarettes smoked are by people with a ‘past-month’ mental health diagnosis. 44% of all cigarettes smoked are by people with a ‘past-month’ mental health diagnosis. Lasser et. Al. 2000

3. Nicotine Dependence and Psychiatric Disorders U.S. Adults National Epidemiologic Survey on Alcohol and Related Conditions National Epidemiologic Survey on Alcohol and Related Conditions Face-to-face interviews (N=43,093) to determine co-occurrence of DSM-IV nicotine dependence and Axis I & II psychiatric disorders Face-to-face interviews (N=43,093) to determine co-occurrence of DSM-IV nicotine dependence and Axis I & II psychiatric disorders NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule – DSM-IV NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule – DSM-IV Current cigarette use = any use in past year. Characterized on days smoked and cigarettes usually smoked Current cigarette use = any use in past year. Characterized on days smoked and cigarettes usually smoked Grant BF. Arch Gen Psychiatry 61:1107, 2004

4. Nicotine Dependence and Psychiatric Disorders U.S. Adults TotalMalesFemales Current smokers 24.9% Nicotine dependence 13%14%11% Alcohol abuse 5%7%3% Alcohol dependence 3%5%2% Grant BF. Arch Gen Psychiatry 61:1107, 2004

5. Prevalence of Psychiatric Disorders Among Respondents with Nicotine Dependence Alcohol use disorder 23% Alcohol abuse 9% Alcohol dependence 13% Major depression 17% Anxiety disorder 22% Personality disorder 32% Grant BF. Arch Gen Psychiatry 61:1107, 2004

6. Prevalence of Nicotine Dependence Among Psychiatric Disorders Alcohol use disorder 34% Alcohol abuse 25% Alcohol dependence 45% Drug use disorder 52% Drug abuse 45% Drug dependence 69% Major depression 30% Anxiety disorder 25% Personality disorder 27% Grant BF. Arch Gen Psychiatry 61:1107, 2004

7. Alcoholism and Smoking Background Regular smoking usually precedes development of alcoholism Regular smoking usually precedes development of alcoholism 2-3x  in prevalence of smoking among substance abusers 2-3x  in prevalence of smoking among substance abusers 10x  in prevalence of alcoholism among heavy smokers vs. nonsmokers 10x  in prevalence of alcoholism among heavy smokers vs. nonsmokers Smoking alcoholics constitute 26% of all smokers Smoking alcoholics constitute 26% of all smokers

15. Alcoholism and Tobacco Dependence Bill Wilson, AA Co-founder “A heavy, sloppy smoker all his life, he developed emphysema in the 1960s. It killed him. He gave his last speech to the International AA Convention in Miami in 1970, lifted to the platform in a wheelchair, gasping for breath and sucking oxygen from the tank that was always with him.” Robertson: Inside Alcoholics Anonymous

16. Mortality Following Inpatient Addictions Treatment Study Design Olmsted County patients admitted for inpatient addictions treatment 1972-1983 Olmsted County patients admitted for inpatient addictions treatment 1972-1983 Follow-up through 1994 – Rochester Epidemiology Project Follow-up through 1994 – Rochester Epidemiology Project Vital status and death certificates Vital status and death certificates CDC classification of alcohol or tobacco- related cause of death CDC classification of alcohol or tobacco- related cause of death Hurt RD, et al. JAMA 275:1097, 1996

17. Mortality Following Inpatient Addictions Treatment Patient Demographics n=845 (65% men, 35% women) n=845 (65% men, 35% women) Mean age at admission – 41.4 years Mean age at admission – 41.4 years 78% alcohol only, 18% alcohol and other drugs 78% alcohol only, 18% alcohol and other drugs 75% current and 8% former smokers 75% current and 8% former smokers Length of follow-up/patient – 10.5  5.6 years (8913 pt/yrs) Length of follow-up/patient – 10.5  5.6 years (8913 pt/yrs) Hurt RD, et al. JAMA 275:1097, 1996

19. Mortality Following Inpatient Addictions Treatment Tobacco or Alcohol Cause of Death PercentObservedExpectedRR Alcohol3473184.1 Tobacco51109532.0 Hurt RD, et al. JAMA 275:1097, 1996

20. Mortality Following Inpatient Addictions Treatment Conclusions High risk for premature mortality High risk for premature mortality Tobacco-related diseases leading cause of death Tobacco-related diseases leading cause of death Treating tobacco dependence is imperative in this high risk group Treating tobacco dependence is imperative in this high risk group Hurt RD, et al. JAMA 275:1097, 1996

21. Treating Alcohol and Tobacco Dependence Simultaneously Design Prospective nonrandomized controlled trial with 1 year abstinence outcomes Prospective nonrandomized controlled trial with 1 year abstinence outcomes Inpatient addictions treatment unit Inpatient addictions treatment unit Control group (n=50) – usual care Control group (n=50) – usual care Intervention group (n=51) Intervention group (n=51) Consultation Consultation Group sessions (5) Group sessions (5) Education sessions (5) Education sessions (5) Telephone follow-up Telephone follow-up Hurt RD, et al. Alcohol Clin Exp Res 18:867, 1994

22. Treating Alcohol and Tobacco Dependence Simultaneously Substance Use History InterventionN=51ControlN=50P Alcohol only (%) 74.554.00.031 Smoking rate (CPD) 25.0  8.7 21.3  10.7 0.052 Smoking onset (age) 14.6  3.7 16.6  5.6 NS Year smoked 26.6  12.4 19.9  10.8 0.012 Hurt RD, et al. Alcohol Clin Exp Res 18:867, 1994

23. Treating Alcohol and Tobacco Dependence Simultaneously Abstinence Outcomes InterventionN=51ControlN=50P No alcohol/drugs at 1 year 68.666NS Not smoking at dismissal 21.610.0NS Not smoking at 1 year 11.800.027 Hurt RD, et al. Alcohol Clin Exp Res 18:867, 1994

24. Treating Alcohol and Tobacco Dependence Simultaneously Conclusions 11.8% tobacco abstinence rate acceptable but can be improved 11.8% tobacco abstinence rate acceptable but can be improved Study run in less than optimal environment Study run in less than optimal environment Perception that it is hard is real Perception that it is hard is real No apparent negative effect on abstinence from alcohol or other drugs No apparent negative effect on abstinence from alcohol or other drugs Unit became tobacco-free after study Unit became tobacco-free after study Hurt RD, et al. Alcohol Clin Exp Res 18:867, 1994

30. Nicotine Patch Therapy in Recovering Alcoholic Smokers Baseline Characteristics Recovering Alcoholics (n=43) Nonalcoholic (n=314) P value CPD 34.1  9.6 28.0  10.4 <0.001 FTQ 9.1  3.2 8.1  3.3 0.022 Baseline nicotine (ng/mL) 22.8  10.7 18.9  12.1 0.007 Baseline cotinine (ng/mL) 305.5  126.7 261.28  118.8 0.049 Hurt RD, et al. Addiction 90:1541, 1995

31. Nicotine Patch Therapy in Recovering Alcoholic Smokers Conclusions More nicotine dependent than nonalcoholics More nicotine dependent than nonalcoholics Can achieve short-term tobacco abstinence with nicotine patch therapy Can achieve short-term tobacco abstinence with nicotine patch therapy May require more intensive intervention: May require more intensive intervention: Dose matching Dose matching Longer treatment Longer treatment  behavioral intervention  behavioral intervention  relapse prevention  relapse prevention Hurt RD, et al. Addiction 90:1541, 1995

32. Nicotine Patch Therapy in Alcoholic Smokers Demographics Nonalcoholic (n=281) Recovering (n=53) Active (n=48) P Age 45.2  1.3 43.8  10.8 42.8  11.2 NS % female 6142370.001 Smoking rate (CPD) 26.4  9.1 30.6  12.1 29.8  11.3 0.004 FTQ 6.9  1.8 8.4  1.7 7.8  1.9 <0.001 Hays JT, et al. Ann Behav Med 21:244, 1999

33. Nicotine Patch Therapy in Alcoholic Smokers Tobacco Abstinence Rates Hays JT, et al. Ann Behav Med 21:244, 1999

34. High Dose Nicotine Patch Therapy in Heavy Smokers Methods Post hoc analysis of 1039 heavy smokers (  30 cpd) Post hoc analysis of 1039 heavy smokers (  30 cpd) Screened for current alcohol problem with short alcohol dependence data questionnaire Screened for current alcohol problem with short alcohol dependence data questionnaire Smokers with alcohol problems in past year were excluded Smokers with alcohol problems in past year were excluded Nicotine patch dose – placebo, 21 mg, 35 mg, or 42 mg Nicotine patch dose – placebo, 21 mg, 35 mg, or 42 mg Higher nicotine patch doses were “slightly more efficacious” Higher nicotine patch doses were “slightly more efficacious” Hughes, JR, et al. Drug Alcohol Depend 71:269, 2003

35. High Dose Nicotine Patch Therapy in Heavy Smokers Past History No problems (n=879) Alcohol Problems (n=160) Age4442 % men 4766 Cigs/day3838 CO (ppm) 3334 FTQ7.98.3 Years smoked 2626 Hughes, JR, et al. Drug Alcohol Depend 71:269, 2003

36. In heavy smokers with or without past history of alcohol problems, no difference in: In heavy smokers with or without past history of alcohol problems, no difference in: time to lapse time to lapse prolonged tobacco abstinence prolonged tobacco abstinence Thus, past history of alcohol problems does not predict a worse outcome Thus, past history of alcohol problems does not predict a worse outcome High Dose Nicotine Patch Therapy in Heavy Smokers Conclusions Hughes, JR, et al. Drug Alcohol Depend 71:269, 2003

37. Bupropion for Smokers with past History of Alcoholism or Depression Results Neither PHMDD nor alcoholism associated with abstinence at EOT (p=0.93) or 1 year (p=0.23) Neither PHMDD nor alcoholism associated with abstinence at EOT (p=0.93) or 1 year (p=0.23) Dose response effect for bupropion at EOT (p<0.001) and 1 year (p=0.02) Dose response effect for bupropion at EOT (p<0.001) and 1 year (p=0.02) Hayford KE, et al. Br J Psychiatry 174:173, 1999

38. Pharmacologic Relapse Prevention for Recovering Alcoholic Smokers Weeks 1-8 Open label tailored nicotine patch therapy (n=195) Bupropion 300 mg/d (n=56) Placebo(n=54) Follow-up Week 52 Week 76 R01 AA-11219

39. Nicotine Patch Dose Based on Serum Cotinine Baseline Serum Cotinine Initial Nicotine Patch Dose, mg/d  200 22 201-30033 > 301 44 Hurt RD, et al. J Stud Alcohol 66:506-516, 2005.

40. Tailored Nicotine Patch Therapy for Recovering Alcoholic Smokers Serum Cotinine Week 2 Patch dose nBaselinen Abstinent subjects n Smoking subjects 22 mg Cotinine25165181257178 % of baseline 77%113% 33 mg Cotinine492573123318291 % of baseline 92%112% 44 mg Cotinine634033636627405 % of baseline 93%101%

41. Tailored Nicotine Patch Therapy for Recovering Alcoholic Smokers Smoking Abstinence Rates 75/195 96/19594/19594/19595/19593/19594/195 100/195 Hurt RD, et al. J Stud Alcohol 66:506-516, 2005.

42. Tailored Nicotine Patch Therapy for Recovering Alcoholic Smokers Smoking Abstinence CP1120196B-1 Abstinent (%) Visit number 7-day point prevalence Continuous Hurt RD, et al. J Stud on Alcohol, 66:506, 2005

43. Tailored Nicotine Patch Therapy for Recovering Alcoholic Smokers Conclusions Excellent 8 week smoking abstinence rate (51%) with tailored nicotine patch therapy Excellent 8 week smoking abstinence rate (51%) with tailored nicotine patch therapy Dosing algorithm works Dosing algorithm works No evidence of nicotine toxicity No evidence of nicotine toxicity Very low rate of relapse to drinking Very low rate of relapse to drinking Hurt RD, et al. J Stud Alcohol 66:506-516, 2005.

44. Nicotine Patch Therapy in Alcoholics Efficacy of 21 or 42 mg x 4 wk (then taper) nicotine patch doses in heavy smokers (N=130) with PH alcoholism Efficacy of 21 or 42 mg x 4 wk (then taper) nicotine patch doses in heavy smokers (N=130) with PH alcoholism FTND score 7.7, mean smoking rate 31.5 cpd FTND score 7.7, mean smoking rate 31.5 cpd Median alcohol abstinence 4 months (69% receiving alcoholism treatment at the time of enrollment) Median alcohol abstinence 4 months (69% receiving alcoholism treatment at the time of enrollment) Longer alcohol abstinence predicted better smoking abstinence outcome Longer alcohol abstinence predicted better smoking abstinence outcome Kalman D, et al. Psychol Addict Behav 18:78-82, 2004

45. Nicotine Patch Therapy in Alcoholics Smoking Abstinence Rates Initial Nicotine Patch Dose Wk 1 Wk 4 Wk 12 21 mg/d 35.4%30.7%20.0% 42 mg/d 30.8%20.0%9.2% Kalman D, et al. Psychol Addict Behav 18:78-82, 2004

48. Treating Alcohol and Tobacco Dependence Rationale to Initiate Treatment During Treatment of other Dependencies Serious cause of morbidity/mortality Serious cause of morbidity/mortality Closely related behaviors Closely related behaviors Eliminates a cue to drink Eliminates a cue to drink Common message Common message Apply same treatment philosophy Apply same treatment philosophy Protected milieu to initiate an attempt Protected milieu to initiate an attempt Many patients in CD programs express interest in stopping tobacco (46-70%) Many patients in CD programs express interest in stopping tobacco (46-70%)

49. Treating Tobacco Dependence in Alcoholics in Treatment or Recovery Meta-analysis of 19 randomized controlled trials Meta-analysis of 19 randomized controlled trials Post-treatment intervention effects (but not long-term) were significant and comparable for patients in addictions treatment or recovery Post-treatment intervention effects (but not long-term) were significant and comparable for patients in addictions treatment or recovery Tobacco dependence interventions provided during addictions treatment  (25%) long- term alcohol and/or drug abstinence Tobacco dependence interventions provided during addictions treatment  (25%) long- term alcohol and/or drug abstinence Prochaska JJ, et al. J Consult Clin Psychol 72:1144-1156, 2004

50. Timing of Alcohol and Smoking Cessation (TASC) Smokers in treatment for alcohol dependence willing to consider stopping smoking Smokers in treatment for alcohol dependence willing to consider stopping smoking Randomized to concurrent treatment or delayed treatment 6 months after alcohol dependence treatment Randomized to concurrent treatment or delayed treatment 6 months after alcohol dependence treatment N=499, mean age 39.2, mean CPD 25.5, FTND 6.0, 47% previously used NRT or bupropion N=499, mean age 39.2, mean CPD 25.5, FTND 6.0, 47% previously used NRT or bupropion Joseph AM. J Addict Dis 22:87-107, 2003

51. Timing of Alcohol and Smoking Cessation (TASC) Smoking Abstinence ITT Concurrent (N=251) Delayed (N=248) P 7 day PP smoking abstinence 3 months 3 months15.5%4.4%<0.0001 6 months 6 months10.8%5.2%0.2 12 months 12.8%10.1%NS 18 months 12.4%13.7%NS Joseph AM. J Stud Alcohol 65:681, 2004

52. Timing of Alcohol and Smoking Cessation (TASC) Alcohol Abstinence ITT Concurrent (N=251) Delayed (N=248) P 30 day alcohol abstinence 6 months 6 months51%64%0.004 12 months 46%53%0.11 18 months 48%60%0.01 6 month alcohol abstinence 6 months 6 months41%56%0.001 12 months 33%42%0.06 18 months 41%48%0.14 Joseph AM. J Stud Alcohol 65:681, 2004

53. Does Smoking Abstinence Threaten Sobriety? 10% of recovering alcoholics state it does 10% of recovering alcoholics state it does 16% report increased craving 16% report increased craving 18% relapse to alcohol/drug use during tobacco abstinence 18% relapse to alcohol/drug use during tobacco abstinence 90% state it DOES NOT threaten sobriety 84% report NO increase in craving 82% DO NOT relapse to alcohol/drug use during tobacco abstinence Adapted from John Hughes, 2004

54. Concurrent vs Delayed Treatment for Smoking KalmanN=36 Delayed less likely to enter smoking tx No difference in smoking outcomes Delayed had worse alcohol outcomes (p=.07) Joseph N=499 Delayed less likely to enter smoking tx No difference in smoking outcomes Concurrent had worse alcohol outcomes (p <.01) Kalman D. J Subst Abuse Treat. 2001;20:233 Joseph AM. J Stud Alcohol. 2004;65:681

55. Unanswered Questions Adequacy of brief treatments? Adequacy of brief treatments? Concurrent vs. delayed treatment? Concurrent vs. delayed treatment? Integrating 12 step and behavioral therapies? Integrating 12 step and behavioral therapies? Interventions for peer resistance? Interventions for peer resistance? Prophylactic treatment to prevent alcohol remission? Prophylactic treatment to prevent alcohol remission? BUT... Postponing treatment means potentially never

56. Treating Tobacco Dependence in Recovering Alcoholics Keep tobacco use on the problem list Keep tobacco use on the problem list Motivate every few months using personal risks and discussing barriers Motivate every few months using personal risks and discussing barriers Utilize past success strategies Utilize past success strategies Associate with non-tobacco using friends Associate with non-tobacco using friends Consider an ex-tobacco user as a “sponsor” Consider an ex-tobacco user as a “sponsor”

57. Treating Tobacco Dependence in Recovering Alcoholics Recommend proven therapies Recommend proven therapies NRT NRT Bupropion Bupropion Varenicline Varenicline Behavior Therapy Behavior Therapy Social Support Social Support Monitor frequently for relapse Monitor frequently for relapse Let patient decide the timing Let patient decide the timing