Smoking, nicotine dependence and psychiatric disorders

1. Smoking, nicotine dependence and psychiatric disorders Lirio S. Covey, Ph.D. Columbia University New York State Psychiatric Institute New York, NY, U.S.A.

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4. The long-standing view: Tobacco Use Is a Health Risk Factor • Cardiovascular disease • Cancer of multiple organ sites • Pulmonary Disorders • Fetal/infant/childhood morbidity & mortality through second-hand smoke

5. The evolved view: Tobacco Use Is a More than a Risk Factor Tobacco use, in particular, chronic use of tobacco, is a disorder in itself.

6. DSM-IV criteria for nicotine dependence

7. ATTRIBUTES OF DRUG ADDICTION: COMPARISON OF DRUGS OF ABUSE

8. ATTRIBUTES OF DRUG ADDICTION: COMPARISON OF DRUGS OF ABUSE

9. Nicotine, the main pharmacological ingredient in tobacco,affects functioning and structure of the brain.

10. Nicotine has psychoactive effects • Animals (rats, squirrel monkeys) and humans will self-administer intravenous nicotine. • Nicotine acts on mesolimbic dopamine system, as do other drugs of abuse. • Nicotine increases firing of neurons and release of neurotransmitters.

11. Neurochemical Effects of Nicotine DOPAMINE Pleasure NOREPINEPHRINE Arousal ACETYLCHOLINE Arousal, Cognitive Enhancement NICOTINE Memory Improvement VASOPRESSIN SEROTONIN Mood Modulation BETA-ENDORPHIN Reduction of Anxiety and Tension

12. Nicotine/Tobacco dependence is a chronic, relapsing disorder.

13. RELAPSE RATES from Nicotine, Heroin, Alcohol Addiction Hunt, Barnett, Branch J Clin Psychol, 1971

14. Nicotine/Tobacco dependence is difficult to treat.

15. 1000 persons seeking treatment for alcohol or drug dependence treatment were asked about difficulty of quitting substances. 50% said that cigarettes would be harder to quit using then their problem substance. Kozlowski LT, Wilkinson DA, Skinner W et al, JAMA, 1989

16. The “hardening hypothesis”.As the proportion of smokers decreases, in response to negative attitudes about smoking, the segment of the smoking population that has great difficulty stopping smoking is increasingly made up of smokers with psychiatric comorbidity.

17. Depression and Smoking in a 20-year longitudinal study of adults. The Stirling County Study (Murphy et al, 2003, AJP) • Setting: RuralAtlantic Canada • - 1952 to 1992 longitudinal data • Population N = 20,000 • Demographic and psychiatric data • Prevalences comparable to national populations

18. Do you smoke? “A lot and some”Rates between 1952-1992

19. Relation of Cigarette Smoking to Current Depression (O.R., 95% C.I.) 1952 1970 1992 <20/day 0.9 1.3 3.1 (1.7-.5) (0.8- 2.3)(1.8 – 5.2) 20/day 1.3 1.8 3.0 (0.8-3.2)(0.9 – 3.8)(1.7 – 5.2) Magnitude of association increased over time.

20. Substantial co-morbidity between mental illness and nicotine dependence

21. Multiple mental disorders are involved: Depression (unipolar, bipolar) • Anxiety disorders (generalized anxiety disorder, phobias, obsessive compulsive disorder, post traumatic stress disorder) • Schizophrenia • Antisocial personality disorder • Conduct disorder and ADHD • Alcohol dependence • Drug dependence

22. In U.S., • 20% have a lifetime history of a mental disorder. • 44% of all cigarette smoking done by persons with lifetime history of mental illness. Lasser et al, JAMA, 2000

23. Prevalence of Current Smokers U.S. National Comorbidity Survey Lasser et al, JAMA, 2000 % 41.0 34.8 22.5 No Mental Lifetime Past Month Illness Mental Illness Mental Illness

24. Quit rates by mental illness historyLasser et al, JAMA, 2000 42.5 37.1 30.5 None Ever Ill Past month .

25. Prevalence of Current SmokingLasser, JAMA, 2000 %

26. Prevalence of Current SmokingLasser, JAMA, 2000 %

27. Smoking status and psychiatric lifetime diagnosis – Odds Ratios relative to never smokers (Germany) P<0.001 P<0.001 P<0.001 P<0.05 N=913, Lubeck, Germany John U et al, 2004, Drug Alc Dependence

28. Prevalence of current smoking according to diagnosis: in-patient and out-patients, Paris, France General Substance Schizophrenia Anxiety Mood Population Poirier M, et al, 2002, Prog in Neuro-Psychopharm Biol Psychiatry

29. Odd Ratios of Nicotine Dependence and Psychiatric Disorders in the U.S. Grant et al, 2004, Arch Gen Psychiatry

30. Major Depression • More smokers among depressed persons • More depression among smokers • Higher nicotine dependence level • Greater difficulty in stopping • Higher frequency and intensity of withdrawal symptoms • Higher risk of post-cessation depression (relapse)

31. Schizophrenia • High prevalence of smoking – 80-95% • Very low rates of complete abstinence • Smoking ameliorates symptoms • Smoking ameliorates medication side effects • Responsive and tolerant to NRT and bupropion

32. Anxiety Disorders Generalized anxiety disorder Obsessive compulsive disorder Post traumatic stress disorder Phobias

33. Anxiety Disorders • Many smokers believe that smoking reduces anxiety level. • Few studies have included sizable numbers of smokers with Anxiety Disorders.

34. Anxiety Disorders • Breslau et al, 1991 • In a study of 1,200 young adults, increased odds ratios for nicotine dependence were found for obsessive compulsive disorder, agoraphobia, and phobia.

35. Anxiety Disorders • Covey et al, 1994 • In a survey of 3,000 men and women (NIMH-ECA), Generalized Anxiety Disorder was associated with: • Ever smoking • Quit smoking

36. Anxiety Disorders • Cinciripini et al, 1995 • Post-hoc analysis according to anxiety level at baseline. • Lower abstinence rate among smokers with high anxiety symptoms.

37. Anxiety Disorders • Dudas et al, 2005, J R Social Health • 215 adolescents age 14-18 years • More anxiety and depressive symptoms among smokers than non-smokers.

38. Anxiety Disorders • West R, Hajek P, Am J Psychiatry 1997 • Study of 101 smokers making a quit attempt. • No increase in anxiety among those who stopped smoking. • Decrease in anxiety from first week of abstinence.

39. Anxiety and smoking:a paradoxical relationship • Smokers say they are calmed by smoking, yet report high average levels of stress. • Stress levels become reduced after smoking cessation. Parrot AC, Int J Addiction, 1995

40. Anxiety and smoking:a paradoxical relationship • Stress levels become reduced after smoking cessation - because the former smoker no longer suffers from the adverse mood effects of acute nicotine withdrawal. • Acute nicotine deprivation (i.e., between cigarettes) leads to increased stress. • Smokers then use cigarettes to reverse these withdrawal effects and "normalize" their mood. • Dependent smokers need regular hits of nicotine just to remain feeling normal. Parrot AC, Int J Addiction, 1995

41. Anxiety and smoking Return to “normal mood” Return to smoking Return to smoking “Normal mood” Nicotine deprivation Nicotine deprivation Withdrawal (anxiety) Withdrawal (anxiety)

42. Anxiety and smoking Return to “normal mood” Return to smoking Return to smoking “Normal mood” Nicotine deprivation Nicotine deprivation Withdrawal (anxiety) Withdrawal (anxiety) Continued abstinence Return to TRUE NORMAL MOOD

43. Attention Deficit Disorder-Hyperactivity (ADHD) Inattention Hyperactivity - Impulsivity Impairment in at least 2 settings (e.g. school, work, home) Symptoms begin in childhood

44. Attention Deficit Disorder-Hyperactivity (ADHD) • Recognized in children in early 1900s. • In the U.S., affects 5% to 10% of children. • Persistence in adulthood – in the 1970s. • Persistence of 50% to 60% to adulthood. • 2% to 4% of adults (7 million)

45. ADHD and Smoking • Cigarette smoking and nicotine dependence are twice as common in adults with ADHD. • Pomerleau OF et al, 1995, J Substance Abuse • Smoking, earlier age of smoking onset, greater amount in children with ADHD than no ADHD. • Milberger S et al, 1997, J Am Acad Child Ad Psych. • Neuropsychological deficits improved with nicotine administration. • Potter and Newhouse, 2004, Psychopharmacol.

46. ADHD and Smoking • Maternal smoking (during pregnancy) associated with hyperactivity, ADHD symptoms, ADHD. • With adjustment for sex, family structure, socioeconomic status, maternal age, and maternal alcohol use (odds ratio 1.30; 1.08-1.58). • Kotimaa AJ, 2003, J Am Acad Child Adol Psych. • Linnet KM, 2003, Am J Psychiatry

47. Alcohol Dependence

48. Prevalence of Current SmokingLasser, JAMA, 2000 %

49. Alcohol Dependence • Higher rates of current smoking – 80% to 95% • Common genetic vulnerability to nicotine and alcohol dependence suggested in twin data.

50. Alcohol Dependence • Many want to quit (up to 100% in one clinical study) • Quit rates in active drinkers lower than in nonalcoholics. • Quit rates in recovering groups same as nonalcoholics.