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.

2. and STAY QUIT! STOP SMOKING (212) 543-5905
Take part in research studies
at no cost to you.
Zyban, Nicotine Patch, Medical Exam, Counseling
The Smoking Cessation Clinic at
Columbia University
Se requiere leer ingles.

3. Le gustaría DEJAR de FUMAR?
COMO??
Por medio de un estudio de investigación con tratamientos para
DEJAR de FUMAR
 Recibirás completamente gratis:
·       Examén Médico
·       Concejería
·       Zyban + Parches de Nicotina
No lo dejes para más tarde!! Llama al: (212)
The SMOKING CESSATION CLINIC at COLUMBIA UNIVERSITY
Se requiere leer inglés.

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
Tolerance +
Withdrawal (Anxiety, Anger, Concentration D, Restlessness, Sleep Disturbance,Appetite Increase)
Taken in larger amounts or longer than intended
Difficulty quitting or cutting down
Much time spent to obtain the substance
Important activities given up
Continued use despite harmful consequences

7. ATTRIBUTES OF DRUG ADDICTION: COMPARISON OF DRUGS OF ABUSE
Heroin
Cocaine
Alcohol
Caffeine
Psychoactive effects +
Drug-reinforced behavior
Compulsive Use
Use despite harmful effects
Relapse after abstinence -
Recurrent drug cravings
Tolerance
Physical dependence
Agonist useful in treating dependence

8. ATTRIBUTES OF DRUG ADDICTION: COMPARISON OF DRUGS OF ABUSE
Nicotine
Heroin
Cocaine
Alcohol
Caffeine
Psychoactive effects +
Drug-reinforced behavior
Compulsive Use
Use despite harmful effects
Relapse after abstinence -
Recurrent drug cravings
Tolerance
Physical dependence
Agonist useful in treating dependence

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
VASOPRESSIN
Memory Improvement
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”
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
Depression and Smoking in a 20-year longitudinal study of adults. The Stirling County Study (Murphy et al, 2003, AJP)
Setting: Rural Atlantic Canada
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.)
<20/day
(1.7-.5) ( ) (1.8 – 5.2)
20/day
( ) (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. 20% have a lifetime history of a mental disorder.
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 history Lasser et al, JAMA, 2000
42.5
37.1
30.5
None Ever Ill Past month .

25. Prevalence of Current Smoking Lasser, JAMA, 2000%

26. Prevalence of Current Smoking Lasser, JAMA, 2000%

27. Smoking status and psychiatric lifetime diagnosis – Odds Ratios relative to never smokers (Germany)
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 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 Return “normal Return “Normal to mood”
Nicotine
deprivation
Nicotine
deprivation
Withdrawal
(anxiety)
Withdrawal
(anxiety)

42. Anxiety and smoking Return to “normal mood” Return to smoking Return
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; ).
Kotimaa AJ, 2003, J Am Acad Child Adol Psych.
Linnet KM, 2003, Am J Psychiatry

47. Alcohol Dependence

48. Prevalence of Current Smoking Lasser, 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.

51. Alcohol Dependence Kalman D, 2004 Psychol Addict Beh
Abstinence rate related with length of alcohol abstinence.

52. Kalman D, 2004, Psychol Addict Beh
12 Mo
3-5 Mo
6-11 Mo
2 Mo

53. Alcohol Dependence New evidence – Joseph et al, 2003
Comparison of concurrent versus delayed smoking abstinence among alcoholics in treatment
More relapse to alcohol with concurrent abstinence
Warrants replication.

54. Drug Dependence

55. Prevalence of Current Smoking Lasser, JAMA, 2000%

56. Drug Dependence High rates of current smoking (comorbidity)
70% in cannabis dependent
75% in cocaine dependent
85%-98% in methadone-maintained
Extremely high levels of nicotine dependence
Genetic, social, environmental factors implicated.

57. Drug Dependence Claim that quitting smoking is hardest
Strong levels of interest in quitting

58. 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

59. Drug Dependence:Marijuana
Any history of cannabis use predictive of relapse to cigarette smoking.
Current tobacco users do not respond to marijuana treatment as well as former or non-tobacco users.

60. Drug Dependence: Cocaine
Among cocaine dependent persons, tobacco users smoke more cocaine and on more days than non-tobacco users.
Tobacco use associated with route of cocaine administration (more smoking and injection of cocaine).
Cessation of cocaine use associated with reduction in number of cigarettes used.

61. Drug Dependence: Opiates/Methadone
Nicotine replacement treatments are helpful. Quit rates (32% at 12 weeks, Frosch et al, 1997) with NRT, similar to rates in non-drug dependent smokers.
Naltrexone, an opioid antagonist, is suggested as possibly helpful smoking cessation aid for opiate dependent smokers.

62. Drug Dependence
High comorbidity between nicotine dependence and drug dependence.
Bi-directional dynamic is apparent.
Genetic, social, environmental factors implicated.
No empirically based treatments for smokers with drug dependence.
Desirability of concurrent treatment is unclear.

63. Issues in treating tobacco use among smokers with substance use disorders
Tobacco use is not recognized as a disorder.
Presumption of low interest in quitting
Fear that tobacco withdrawal symptoms may jeopardize sobriety (alcohol/drug dependence)
Continued use of psychoactive non-nicotine substance reduces ability to quit tobacco
There is a paucity of evidence-based treatment approaches
Lack of knowledge and training in smoking cessation treatment approaches

64. Treatment issues for Alcohol Dependent smokers
Bupropion (Zyban) same results as for nonalcoholic smokers
Nicotine replacement agents
Cognitive behavioral treatment for mood management helps alcoholic smokers with history of major depression
12-step program enhanced effect of standard counseling treatment

65. Treatments issues for drug dependent smokers
Studies indicate high level of interest in cessation.
No reliable data is available. Few studies have been carried out.
There is great need to develop and
implement smoking cessation
interventions for this group of smokers.

66. Mechanisms of Association
Mental Illness
Smoking
Common Diathesis

67. Proposed mechanisms underlying comorbidity: 1. Causal
MENTAL
ILLNESS
SMOKING
Nicotine induces CNS alterations.
MENTAL
ILLNESS
SMOKING
Nicotine medicates symptoms.

68. Proposed mechanisms underlying comorbidity: 2. Shared etiology
GENES, e.g.
DRD2, DRD1
ENVIRONMENT, e.g.
Childhood adversity
Familial factors (relationships, modeling)
Peer aggregation

69. Smoking “medicates” psychopathology
Author, yr
Sample
Condition
Patton, 1998
14-15 yrs
Depression, anxiety
Lerman, 2001
Adults
Inattention symptoms
Lerman, 1996
Negative affect
Tizabi, 1999
Rats
Depression (FSL rats)
Martinez-Gonzales, 2001
Depression and alcohol use

70. Does depression influence smoking initiation. YES
Does depression influence smoking initiation? YES. Cohort 1 ( ), Stirling County study %
Initiation %
Initiation

71. Does depression influence smoking initiation. YES
Does depression influence smoking initiation? YES. Cohort 2 ( ), Stirling County study %
Initiation %
Initiation

72. Tobacco use leads to psychopathology
Author, yr
Sample
Diagnosis
Wu & Anthony,1999
Teens
Depressive Symptoms
Goodman & Capitan, 1999
Choi et al, 1997
Brown et al, 1996
MDD & Drug Abuse/Dependence
Breslau & Klein, 2000
Young adults
Panic disorder
Johnson et al, 2000
Agoraphobia,GAD

73. Does smoking precede depression? Stirling County study
Baseline Incidence of new status depression per 1000
Cohort 1 Smokers
Nonsmokers
Cohort 2 Smokers 3.8
Nonsmokers 3.5
The evidence suggests NO.

74. Shared etiology Author, yr Sample Diagnosis/Outcome Breslau, 1993
Young adults
MDD – ND relationship non-causal, a third factor
Kendler, 1993
Female twins
MDD - Genetic (vs familial, environmental) best model
Dierker, 2002
Probands & 1st degree relatives
Dysthymia & heavy smoking cross-aggregated in families
True, 1999
Male twins
R=0.68 genetic correlation for nicotine and alcohol dependence

75. Which explanatory mechanism is true?

76. Implications Because smoking may lead to mental illness: Prevention
Is teen-smoking a screen for psychopathology?
(Smoking status a clinical tool for psychiatry)
Will smoking prevention or early cessation
reduce risk of mental illness ?
Treatment
Will cessation reduce symptoms of mental illness?

77. Implications
Because Mental Illness may lead to smoking, or etiology is shared:
Prevention
Are psychiatric symptoms markers of risk for future nicotine dependence ?
Will early treatment of mental illness prevent/reduce
nicotine dependence?
Treatment
Smokers with mental illness will require intensive cessation treatments, of longer duration :
- higher doses,
- combination treatments (e.g. Bupr & NRT),
- longer duration (6 months vs 8-12 weeks)