Download Smoking, nicotine dependence and psychiatric disorders

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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The long-standing view:
Tobacco Use Is a Health Risk Factor
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Cardiovascular disease
Cancer of multiple organ sites
Pulmonary Disorders
Fetal/infant/childhood morbidity &
mortality through second-hand smoke
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.
DSM-IV criteria for nicotine dependence
Nicotine
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
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ATTRIBUTES OF DRUG ADDICTION:
COMPARISON OF DRUGS OF ABUSE
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
Heroin
Cocaine
Alcohol
Caffeine
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ATTRIBUTES OF DRUG ADDICTION:
COMPARISON OF DRUGS OF ABUSE
Nicotine
Psychoactive effects
Heroin Cocaine Alcohol Caffeine
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Relapse after
abstinence
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Recurrent drug
cravings
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Tolerance
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Drug-reinforced
behavior
Compulsive Use
Use despite harmful
effects
Physical dependence
Agonist useful in
treating dependence
Nicotine, the main pharmacological
ingredient in tobacco,
affects
functioning and structure of the brain.
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.
Neurochemical Effects of Nicotine
DOPAMINE
Pleasure
NOREPINEPHRINE
Arousal, Cognitive Enhancement
ACETYLCHOLINE
NICOTINE
Memory Improvement
VASOPRESSIN
SEROTONIN
Arousal
Mood Modulation
BETA-ENDORPHIN
Reduction of Anxiety and Tension
Nicotine/Tobacco dependence is a
chronic, relapsing disorder.
RELAPSE RATES from
Nicotine, Heroin, Alcohol Addiction
100
90
80
70
60
50
40
30
20
10
0
NICOTINE
HEROIN
EOT
3 MOS
ALCOHOL
6 MOS
12 MOS
Hunt, Barnett, Branch J Clin Psychol, 1971
Nicotine/Tobacco dependence is
difficult to treat.
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
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.
Depression and Smoking in a
20-year longitudinal study of adults.
The Stirling County Study
(Murphy et al, 2003, AJP)
Setting: Rural Atlantic Canada
- 1952 to 1992 longitudinal data
- Population N = 20,000
- Demographic and psychiatric data
- Prevalences comparable to national populations
Do you smoke? “A lot and some”
Rates between 1952-1992
50
45
40
35
30
25
20
15
10
5
0
All Ss
1952
1970
1992
Relation of Cigarette Smoking to Current
Depression (O.R., 95% C.I.)
1952
1970
1992
<20/day
0.9
(1.7-.5)
1.3
(0.8- 2.3)
3.1
(1.8 – 5.2)
20/day
1.3
(0.8-3.2)
1.8
(0.9 – 3.8)
3.0
(1.7 – 5.2)
Magnitude of association increased over time.
Substantial co-morbidity between mental
illness and nicotine dependence
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
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
Prevalence of Current Smokers
U.S. National Comorbidity Survey
Lasser et al, JAMA, 2000
45
40
%
35
30
25
20
15
10
22.5
34.8
41.0
5
0
No Mental
Illness
Lifetime
Mental Illness
Past Month
Mental Illness
Quit rates by mental illness history
Lasser et al, JAMA, 2000
45
40
35
30
25
42.5
37.1
20
30.5
15
10
5
0
None
Ever Ill
.
Past month
Prevalence of Current Smoking
Lasser, JAMA, 2000
45
40
35
30
% 25
20
15
10
5
0
Major Depression
Alcohol
Dependence
Drug
Dependence
No Mental Illness
Prevalence of Current Smoking
Lasser, JAMA, 2000
50
45
40
35
%30
25
20
15
10
5
0
GAD
PTSD
Simple
Phobia
Panic
Attacks
No Mental
Illness
Smoking status and psychiatric lifetime diagnosis –
Odds Ratios relative to never smokers (Germany)
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
P<0.001
P<0.001
Substance Use
Affective
Disorders
P<0.001
P<0.05
Anxiety
Disorders
Somatoform
N=913, Lubeck, Germany John U et al, 2004, Drug Alc Dependence
Prevalence of current smoking according to
diagnosis: in-patient and out-patients, Paris, France
100
90
80
70
60
50
40
30
20
10
0
General
Population
Substance
Schizophrenia
Anxiety
Poirier M, et al, 2002, Prog in Neuro-Psychopharm Biol Psychiatry
Mood
Odd Ratios of Nicotine Dependence and
Psychiatric Disorders in the U.S.
16
14
12
10
8
6
4
2
0
Drug
Alcohol
Dependence Dependence
Mood
Disorder
Anxiety
Disorder
Grant et al, 2004, Arch Gen Psychiatry
Personality
Disorder
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)
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
Anxiety Disorders
Generalized anxiety disorder
Obsessive compulsive disorder
Post traumatic stress disorder
Phobias
Anxiety Disorders
• Many smokers believe that smoking reduces
anxiety level.
• Few studies have included sizable numbers
of smokers with Anxiety Disorders.
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.
Anxiety Disorders
• Covey et al, 1994
– In a survey of 3,000 men and women (NIMHECA), Generalized Anxiety Disorder was
associated with:
• Ever smoking
• Quit smoking
Anxiety Disorders
• Cinciripini et al, 1995
• Post-hoc analysis according to anxiety level at
baseline.
• Lower abstinence rate among smokers with high
anxiety symptoms.
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.
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.
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
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
Anxiety and smoking
“Normal
mood”
Nicotine
deprivation
Return
to
smoking
Withdrawal
(anxiety)
Return
to
“normal
mood”
Nicotine
deprivation
Return
to
smoking
Withdrawal
(anxiety)
Anxiety and smoking
“Normal
mood”
Nicotine
deprivation
Return
to
smoking
Withdrawal
(anxiety)
Continued
abstinence
Return
to
“normal
mood”
Nicotine
deprivation
Return
to
smoking
Withdrawal
(anxiety)
Return to TRUE
NORMAL MOOD
Attention Deficit DisorderHyperactivity (ADHD)
Inattention
Hyperactivity - Impulsivity
Impairment in at least 2
settings (e.g. school,
work, home)
Symptoms begin in childhood
Attention Deficit DisorderHyperactivity (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)
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.
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
Alcohol Dependence
Prevalence of Current Smoking
Lasser, JAMA, 2000
45
40
35
30
% 25
20
15
10
5
0
Major Depression
Alcohol
Dependence
Drug
Dependence
No Mental Illness
Alcohol Dependence
• Higher rates of current smoking – 80%
to 95%
• Common genetic vulnerability to nicotine
and alcohol dependence suggested in twin
data.
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.
Alcohol Dependence
• Kalman D, 2004 Psychol Addict Beh
– Abstinence rate related with length of
alcohol abstinence.
Kalman D, 2004, Psychol Addict Beh
12 Mo
3-5 Mo
6-11 Mo
2 Mo
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.
Drug Dependence
Prevalence of Current Smoking
Lasser, JAMA, 2000
45
40
35
30
% 25
20
15
10
5
0
Major Depression
Alcohol
Dependence
Drug
Dependence
No Mental Illness
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.
Drug Dependence
• Claim that quitting smoking is hardest
• Strong levels of interest in quitting
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
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.
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.
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 nondrug dependent smokers.
• Naltrexone, an opioid antagonist, is
suggested as possibly helpful smoking
cessation aid for opiate dependent smokers.
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.
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
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
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.
Mechanisms of Association
Mental Illness
Common Diathesis
Smoking
Proposed mechanisms underlying
comorbidity:
1. Causal
MENTAL
SMOKING
ILLNESS
Nicotine induces CNS alterations.
MENTAL
SMOKING
ILLNESS
Nicotine medicates symptoms.
Proposed mechanisms underlying
comorbidity: 2. Shared etiology

GENES, e.g.
 DRD2, DRD1

ENVIRONMENT, e.g.
 Childhood adversity
 Familial factors
(relationships, modeling)
 Peer aggregation
Smoking “medicates” psychopathology
Author, yr
Sample
Condition
Patton, 1998
14-15 yrs
Depression, anxiety
Lerman, 2001
Adults
Inattention
symptoms
Lerman, 1996
Adults
Negative affect
Tizabi, 1999
Rats
Depression (FSL
rats)
Depression and
alcohol use
Martinez-Gonzales, Rats
2001
Does depression influence
smoking initiation? YES.
Cohort 1 (1952-1970), Stirling County study
8
7
6
5
4
3
%
Initiation
%
Initiation
2
1
0
Never Depressed
Depressed
Does depression influence
smoking initiation? YES.
Cohort 2 (1970-1992), Stirling County study
7
6
5
%
Initiation
4
3
2
1
0
%
Initiation
Never Depressed
Depressed
Tobacco use leads to psychopathology
Author, yr
Sample
Diagnosis
Wu &
Anthony,1999
Teens
Depressive
Symptoms
Goodman &
Capitan, 1999
Teens
Depressive
Symptoms
Choi et al, 1997
Teens
Brown et al, 1996
Teens
Depressive
Symptoms
MDD & Drug
Abuse/Dependence
Breslau & Klein,
Young adults
2000
Johnson et al, 2000 Teens
Panic disorder
Agoraphobia,GAD
Does smoking precede depression?
Stirling County study
Baseline
status
Incidence of new
depression per 1000
Cohort 1
1952-1970
Smokers
Nonsmokers
4.5
4.6
Cohort 2
1970-1992
Smokers
Nonsmokers
3.8
3.5
The evidence suggests NO.
Shared etiology
Author, yr
Sample
Diagnosis/Outcome
Breslau, 1993
Young
adults
MDD – ND relationship
non-causal, a third factor
Kendler, 1993
Female
twins
Dierker, 2002
True, 1999
MDD - Genetic (vs
familial, environmental)
best model
Probands & Dysthymia & heavy
1st degree
smoking cross-aggregated
relatives
in families
Male twins
R=0.68 genetic correlation
for nicotine and alcohol
dependence
Which explanatory mechanism
is true?
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?
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)