Nicotine dependence in the mental health population
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Nicotine Dependence in the Mental Health Population. Overview. Neurobiology of addiction Nicotine addiction Nicotine withdrawal Smoking and psychiatric disorders: overview Specific disorders Depression Suicide Schizophrenia Generalized anxiety disorder (GAD) Panic disorder.

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Nicotine dependence in the mental health population

Nicotine Dependence in the Mental Health Population


Overview

Overview

  • Neurobiology of addiction

  • Nicotine addiction

  • Nicotine withdrawal

  • Smoking and psychiatric disorders: overview

  • Specific disorders

    • Depression

    • Suicide

    • Schizophrenia

    • Generalized anxiety disorder (GAD)

    • Panic disorder


Neurobiology of addiction

Neurobiology of Addiction


Stages of addiction

Begins with social drug taking and acute reinforcement

Pattern of escalating compulsive use

Dependence

Stages of Addiction

Acute Reinforcement/Social Drug Taking

GeneticVariables

Environmental Factors

Stress

Conditioning Effects

Escalating/Compulsive Use

Relapse

Dependence

Withdrawal

Protracted Withdrawal

Recovery?

Le Moal et al. Eur Neuropsychopharmacol. 2007;17:377-393.


Spiraling cycle of addiction dsm iv

PreoccupationAnticipation

Preoccupation with obtainingPersistent physical or psychological problems

Taken inlarger amountsthan intended

WithdrawalNegative Affect

Persistent desire

BingeIntoxication

Tolerance withdrawal

Social, occupational, or recreational

activities compromised

Spiraling Distress

Addiction

Spiraling Cycle of Addiction (DSM-IV)

  • The 3 major components of the addiction cycle are preoccupation–anticipation, binge–intoxication, and withdrawal–negative affect

  • The cycle is conceptualized as a spiral that increases in amplitude with repeated experience, ultimately resulting in the pathologic addictive state

Koob. Eur Neuropsychopharmacol. 2003;13:442-452.


Neurocircuits that underlie addiction

Neurocircuits That Underlie Addiction

Drug-Seeking Behavior

Motor Cortex

Prefrontal CortexAnterior CingulatePrelimbic CortexOrbitofrontal Cortex

Drug and CueReinstatement:“Craving”

Thalamus

BasolateralAmygdala

Behavioral Output:“Compulsivity”

Pallidum

Central Nucleusof Amygdala

Bed Nucleus ofStria Terminalis

ENK

DA

Drug-AssociatedReinforcement:“Reward” and “Stress”

Nucleus Accumbens (nAcc)

ENK

DA

CRF

CRF

ENK

NE

NE

DA

-END

Pontine Nuclei

Arcuate

VTA

NE=norepinephrine, ENK=enkephalin, CRF=corticotropin-releasing factor, DA=dopamine, -END=-endorphin.Le Moal et al. Eur Neuropsychopharmacol. 2007;17:377-393.


Neurobiologic basis for relapse

Relapse occurs in response to stimulation by compulsive drive circuits and deficits in inhibitory restraint

Neurobiologic Basis for Relapse

Compulsive Drive Circuits

Inhibitory ControlDeficits

  • Priming

  • Drug cues

  • Obsessive thoughts (craving)

  • Stress

  • Impulsivity (automaticity)

  • Decision making

Adinoff. Harv Rev Psychiatry. 2004;12:305-320.


Summary neurobiology of addiction

Summary: Neurobiology of Addiction

  • Addiction is a multistep process

  • Multiple neurocircuits are involved in the craving, reward, stress, and compulsivity associated with addiction

  • Relapse occurs in response to stimulation by compulsive drive circuits and deficits in inhibitory restraint


Nicotine dependence

Nicotine Dependence

  • Action of nicotine in the central nervous system

  • Neurobiologic and physiologic effects of tobacco dependence


Nicotine dependence dsm iv tr criteria

3 or more of the following symptoms within a 1-year time span:

Tolerance to nicotine with decreased effect and increasing dose to obtain same effect

Withdrawal symptoms with cessation

Persistent desire to smoke despite efforts to decrease intake

Extensive time spent smoking or purchasing tobacco

Postponing work, social, or recreational events in order to smoke

Continuing to smoke despite health hazards

Nicotine Dependence: DSM-IV-TR Criteria

N

CH3

N

Nicotine

American Psychiatric Association. Diagnostic and Statistical Manual of Mental DisordersFourth Edition Text Revision. Washington, DC: American Psychiatric Association; 2000; http://www.intox.org/databank/documents/supplem/supp/sup2.htm. Accessed October 19, 2007.


Neuronal nicotine acetylcholine receptor

Nicotine binds preferentially to nicotinic acetylcholinergic receptors (nAchRs) in the central nervous system

When nicotine binds to the nAChR, the receptor complex undergoes a conformational change, allowing the channel gate to open, permitting the passage of cations, resulting in signal transmission

H2N

HOOC

Neuronal Nicotine Acetylcholine Receptor

Ligand binding site

NH2

COOH

H2N

COOH

M1

Extracellular

M2

B

A

M3

Cytoplasmic

M4

PresynapticnAChRs

PostsynapticnAChRs

C

PreterminalnAChRs

Laviolette et al. Nat Rev Neurosci. 2004;5:55-65.


Mechanism of action of nicotine in the central nervous system

The 42 nicotinic receptor in the VTA mediates the effects of nicotine in the central nervous system

After nicotine binds to the 42 nicotinic receptor in the VTA, it results in a release of dopamine in the nAcc, which is believed to be linked to reward

b2

b2

a4

a4

b2

4b2

Nicotinic receptor

NIC

nAcc

Nicotine -

Ventraltegmental area(VTA)

Dopamine -

Mechanism of Action of Nicotine in the Central Nervous System

nAcc= Nucleus Accumbens. Adapted from Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125.


Nicotine stimulates dopamine release

D

D

D

D

– β2 subunit

containing nAChR

- Nicotine

- Dopamine

D

Nicotine Stimulates Dopamine Release

  • Nicotine activates 42 nicotinic receptors in the VTA, resulting in dopamine release at the nAcc. This may result in the short-term reward/satisfaction associated with cigarette smoking

Reward

D

Axon

VTA

nAcc

nAcc= Nucleus Accumbens; VTA= Ventral Tegmental Area.

Adapted from Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125.


Role of dopamine in nicotine addiction

Role of Dopamine in Nicotine Addiction

NH2

  • Rewarding effects of nicotine are dependent on mesolimbic dopamine-mediated transmission

  • In nicotine-dependent patients, the drive for continued drug use results from the need for heightened dopamine concentrations

OH

OH

Dopamine

Adinoff. Harv Rev Psychiatry. 2004;12:305-320. http://www.biopsychiatry.com/dopamine/dopamine.jpg. Accessed May 1, 2007.


Chronic nicotine exposure up regulation of nicotine receptors

D

D

D

D

D

D

D

D

D

– β2 subunit

containing nAChR

- Nicotine

- Dopamine

D

Chronic Nicotine Exposure: Up-Regulation of Nicotine Receptors

  • With chronic exposure, nicotine stimulates 42 nicotinic receptor activation and desensitization, followed by 42 nicotinic receptor up-regulation and an increase in the number of 42 nicotinic receptors

Reward

D

Axon

VTA

nAcc

Adapted from Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125; Corringer et al. J Phys Paris. 2006;99:162-171.


The cycle of nicotine addiction

Dopamine

Nicotine

The Cycle of Nicotine Addiction

  • Nicotine binding causes an increase in release of dopamine

  • Dopamine gives feelings of pleasure and calm

  • The dopamine decrease between cigarettes leads to withdrawal symptoms of irritability and stress

  • The smoker craves nicotine to restore pleasure and calmness

  • Smokers generally titrate their smoking to achieve maximal stimulation and avoid symptoms of withdrawal and craving

Jarvis. BMJ. 2004;328:277-279; Picciotto et al. Nicotine Tob Res. 1999;1:S121-S125.


Role of environmental stimuli in nicotine dependence

Role of Environmental Stimuli in Nicotine Dependence

  • Environmental/social stimuli associated with smoking play a role in reinforcing nicotine dependence

  • Nonnicotine stimuli are important in both motivating and maintaining smoking behavior

  • Role of environmental vs pharmacologic stimuli in nicotine dependence varies between men and women

Direct pharmacologic effects of nicotine are necessary but not sufficient to explain tobacco dependence; these effects must take into account the environmental/social context in which the behavior occurs

Caggiula et al. Physiol Behav. 2002;77:683-687.


Summary nicotine dependence

Summary: Nicotine Dependence

  • Nicotine dependence is a well-defined addictive disorder

  • Nicotine’s effects on the 42 receptors in the Ventral Tegmental Area (VTA) results in

    • Acute dopamine release and short-term reward

    • Chronic receptor activation, desensitization, and up-regulation

  • The dopaminergically mediated physical and psychological rewards of smoking reinforce repeat behavior

  • Environmental/social stimuli associated with smoking play a role in reinforcing nicotine dependence


Nicotine withdrawal

Nicotine Withdrawal


Nicotine dependence in the mental health population

‘‘Why do people smoke . . . to relax; for the taste; to fill the time; something to do with my hands. . . . But, for the most part, people continue to smoke because they find it too uncomfortable to quit’’Philip Morris, 1984

Philip Morris. Internal presentation. 1984, 20th March; Kenny et al. Pharmacol Biochem Behav. 2001;70:531-549.


Nicotine withdrawal1

Nicotine Withdrawal

  • Nicotine withdrawal syndrome consists of both somatic and affective symptomatology

Withdrawal Syndrome

Irritability, frustration, or anger

Insomnia/sleep disturbance

Anxiety

(may increase or decrease

with quitting)

Increased appetite or weight gain

Dysphoric or depressed mood

Restlessness or impatience

Difficulty concentrating

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision. Washington, DC: American Psychiatric Association; 2000.


Select withdrawal symptoms over time

1

2

3

4

5

6

7

8

9

10

Select Withdrawal Symptoms Over Time

Nicotine Gum

Placebo

Mean Adjusted

Withdrawal Score

Impatience

Irritability/Anger

1.5

1.0

0.5

0.0

Postcessation Weeks

Postcessation Weeks

Mean Adjusted

Withdrawal Score

Anxiety/Tension

Excessive Hunger

Postcessation Weeks

Postcessation Weeks

N = 40. Mean adjusted withdrawal scores are from an analysis of covariance with baseline cigarettes per day and baseline scores on the items shown as covariates.

Gross et al. Psychopharmacology. 1989;98:334-341.


Nicotine withdrawal severity

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Nicotine Withdrawal: Severity

  • Smokers experiencing severe withdrawal have the most pronounced symptoms of depression

Withdrawal Symptoms

Mild

Moderate

Severe

Endorsement Probabilitya

Restlessness

Headaches

Craving Nicotine

Irritability

Nervousness

Hands Shaking

Feeling Drowsy

Upset Stomach

Depressed Mood

Increased Appetite

Heart Slowed Down

Trouble Sleeping

Poor Concentration

aClasses of withdrawal syndrome are defined by groups of respondents who endorsed similar combinations of symptoms.

Estimates of prevalence for different classes of withdrawal were obtained along with expected frequencies of endorsement for each symptom of withdrawal by type.

Madden et al. Addiction. 1997;92(7):889-902.


Severity of withdrawal and psychiatric disorders

Severity of Withdrawal and Psychiatric Disorders

  • Smokers with a history of psychiatric disorders have a higher likelihood of experiencing severe withdrawal

Odds Ratio (95% CI)a

Major Depression

Alcohol

Dependence

Conduct

Disorder

Agoraphobia

SocialPhobia

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Madden. Addiction. 1997;92(7): 889-902.


Summary nicotine withdrawal

Summary: Nicotine Withdrawal

  • Nicotine withdrawal syndrome consists of both somatic and affective symptomatology

  • Smokers experiencing severe withdrawal have the most pronounced symptoms of depression

  • Smokers with a history of psychiatric disorders have a higher likelihood of experiencing severe withdrawal


Smoking and psychiatric disorders overview

Smoking and Psychiatric Disorders: Overview


Prevalence of smoking in the psychiatric population

Prevalence of Smoking in the Psychiatric Population

P<.001

P<.001

Lifetime Smoking Rates (%)

Lasser et al. JAMA. 2000;284(20):2606-2610.


Increased cigarette consumption in smokers with psychiatric disorders

Increased Cigarette Consumption in Smokers With Psychiatric Disorders

Cigarettes/Day

Lasser et al. JAMA. 2000;284(20):2606-2610.


Underdiagnosis of nicotine dependence in the psychiatric setting

Underdiagnosis of “Nicotine Dependence” in the Psychiatric Setting

Mental Health Records

Documented (%)

Peterson et al. Am J Addict. 2003;12:192-197.


Smoking risk factor for psychiatric disorders

Smoking: Risk Factor for Psychiatric Disorders

  • Estimated effects of preexisting daily smoking varies across disorders

Odds Ratio (95% CI)a,b,c

Major Depression

Dysthymia

Panic Disorder

Agoraphobia

GAD=generalized anxiety disorder. These models predict the subsequent onset of specific disorders in all daily smokers, without controlling for other psychiatric disorders that preceded the onset of daily smoking and without taking into account the proximity and intensity of smoking.aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. bFrom a series of 10 survival models for first onset of specific disorders associated with prior daily smoking as time dependent, adjusted for race, sex, age, education, and same-year onset. cP.05.

Breslau et al. Psychol Med. 2004;34:323-333.


Psychiatric disorders in dependent and nondependent smokers

Psychiatric Disorders in Dependent and Nondependent Smokers

  • The associations of psychiatric disorders with tobacco dependence are stronger than with nondependent smoking

Odds Ratio (95% CI)a

b

b

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons; sex adjusted. bAdjusted for other substance dependencies.Breslau. Behav Genet. 1995;25(2):95-101.


Psychiatric disorders odds of progression to nicotine dependence

Psychiatric Disorders: Odds of Progression to Nicotine Dependence

Odds Ratio (95% CI)a

Major Depressionb

PanicDisorder

Agoraphobiab

GADc

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Preexisting disorder is defined as first onset at least 1 year before onset of daily smoking. bP<.05.cGAD= Generalized Anxiety Disorder

Breslau et al. Biol Psychiatry. 2004;55:69-76.


Psychiatry and smoking

Psychiatry and Smoking

Illicit Drug Use

  • Psychiatric patients who smoke have

P=.0000

%

  • Higher incidence of illicit drug use

Noncompliant With Treatment

P=.0000

  • Poorer treatment compliance

%

P=.000

  • Lower Global Assessment Functioning (GAF) score

GAF Score 50

Montoya et al. Am J Addict. 2005;14(5):441-454.


Nicotine addiction social and psychological factors

Nicotine Addiction: Social and Psychological Factors

  • Smoking

    • Accepted part of the culture in many psychiatric treatment facilities

    • Shared social activity

    • Barrier to achieving relationships, employment, and housing for psychiatric patients

Williams et al. Addict Behav. 2004;29:1067-1083; Reuters UK. http://uk.reuters.com/article/personalFinanceNews/idUKNOA82640920070629. Accessed September 25, 2007.


Smoking and psychiatric symptomatology

Smoking and Psychiatric Symptomatology

  • In patients with schizophrenia, smoking may be associated with improvements in specific symptoms and cognitive measures

Compton et al. Harv Rev Psychiatry. 2006;14(4):212-222; Depressed Man_PRinc_SF8575_Reference. http://db2.photoresearchers.com/search/SF8575. Accessed September 28, 2007.


Summary smoking and psychiatric disorders

Summary: Smoking and Psychiatric Disorders

  • Smoking is highly prevalent in the psychiatric population

  • Nicotine-dependent smokers in the mental health population

    • Smoke greater quantities

    • Frequently are underdiagnosed

    • Have a higher incidence of illicit drug use, poorer treatment compliance, and lower GAF scores

    • May derive symptomatic relief from their psychiatric disorders as a result of smoking

  • Estimated effects of preexisting daily smoking varies across disorders

  • Active psychiatric disorders may predict an increased risk of smokers’ progression to nicotine dependence

  • Numerous social and psychological factors play a role in the perpetuation of nicotine dependence in the mentally ill


Smoking and depression

Smoking and Depression


Prevalence of depression

Prevalence of Depression

  • In the United Kingdom, 56% of patients with depression are regular smokers, which is more than double the prevalence rate (26%) in the general population

Depressed Patients

General Population

Nonsmokers

Current Smokers

Farrell et al. Int Rev Psychiatry. 2003;15:43-49; Mackay et al. The Tobacco Atlas. 2nd ed. 2006.


Risk of depression in adolescent smokers

Risk of Depression in Adolescent Smokers

  • In nondepressed adolescents, current cigarette smoking was the strongest predictor of developing high depressiveb symptoms

Odds Ratio (95% CI)a

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.bThose scoring above the cutpoints for the modified Centers for Epidemiologic Studies-Depression Scale (CES-D) were considered to have high depressive symptomatology.

Goodman et al. Pediatrics. 2000;106(4):748-755.


Smoking affects psychomotor performance

Smoking Affects Psychomotor Performance

Pre

Post

Depressed Smokers

Control Smokers

400

400

380

380

360

360

340

340

Mean Reaction Time (ms)a

Mean Reaction Time (ms)a

320

320

300

300

280

280

260

260

0

1

2

3

0

1

2

3

Cigarette

Cigarette

aMean reaction time was measured using a computer-based simple reaction time task. Malpass et al. Psychopharmacology. 2007;190:363-372.


Quitting and depression

Quitting and Depression

  • Smokers with a history of depression are less likely to quit

  • Even minimal levels of depression can affect abstinence after an attempt to quit

POMS Depression 0

1.0

0.9

POMS Depression 1

0.8

0.7

0.6

0.5

Cumulative Proportion Surviving

0.4

0.3

P<.01

0.2

0.1

0.0

0

5

10

15

20

25

30

Days to First Cigarette

POMS=Profile of Mood State is a 65-item measure designed to assess a patient’s current mood state.

Niaura et al. Psychol Addict Behav. 2001;15:13-17.


Summary smoking and depression

Summary: Smoking and Depression

  • Smoking is highly prevalent in patients who have depression

  • Patients with depression may smoke to ameliorate their depressive symptoms

  • Depressed smokers are less likely to successfully quit smoking


Smoking and suicide

Smoking and Suicide


Increased rate of suicide in smokers

Increased Rate of Suicide in Smokers

  • There is a strong association between heavy smoking and high suicide rate

Annual Suicide Rate per 100,000 by Cigarettes Smoked/Day

Never Smokers

Ex-smokers

1-14

15-24

25

Cigarettes/Day

Current Smokers

Men

Doll et al. BMJ. 1994;309:901-911.


Smoking and suicide increased risk

Smoking and Suicide: Increased Risk

P<.001

Relative Risk(95% CI)a

1-14 (n=1333)

15 (n=2241)

Never Smokers

Ex-smokers

Cigarettes/DayCurrent Smokers

aRelative risk was defined as the suicide incidence rate among those with a history of smoking divided by the rate among nonsmokers. Adjusted for time period, age, alcohol intake, and marital status.

Miller et al. Am J Public Health. 2000;90:768-773.


Increased risk of suicidal behavior

Increased Risk of Suicidal Behavior

  • Tobacco use is associated with an increased risk in suicidal behavior among adolescents and adults, independent of other substance use, depressive symptoms, and prior suicidal ideation

P<.05

Odds Ratio (95% CI)a

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed person. Adjusted for history of major depression, alcohol, and drug use disorders.Breslau et al. Arch Gen Psychiatry. 2005;62:328-334.


Smoking and suicide violent vs nonviolent deaths

Smoking and Suicide: Violent vsNonviolent Deaths

  • Smoking is associated with an increased risk of both violentand nonviolent suicide

Nonsmokers

Light/moderate smokers

P<.01

Heavy Smokers

P<.01

P=.05

Relative Risk (95% CI)a

P=.03

Violent Suicides

Nonviolent Suicides

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Tanskanen et al. Acta Psychiatr Scand. 2000;101:243-245.


Suicidal behavior and serotonin

Inverse relationship between the quantity of cigarettes smoked and CSF 5-HIAA (index of serotonin function) (P.003)

Reduced CSF 5-HIAA concentration is independently associated with

History of a higher lethality in suicide attempts

Severity of lifetime aggression

120

100

80

60

40

20

0

Suicidal Behavior and Serotonin

CSF 5-HIAA (pmol/mL)

0

1-20

21-39

40

Cigarettes/DayCurrent Smokers

CSF 5-HIAA=cerebrospinal fluid 5-hydroxyindoleacetic acid.

Malone et al. Am J Psychiatry. 2003;160:773-779; Placidi et al. Biol Psychiatry. 2001;50:783-791.


Adolescent psychiatric inpatients smoking and suicide

Adolescent Psychiatric Inpatients: Smoking and Suicide

Regular Daily Smoking

Odds Ratio (95% CI)a

None

Ambivalent/Mild Attempts

Obvious/Life-Threatening Attempts

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Mäkikyrö et al. J Adolesc Health. 2004;34:250-253.


Nicotine dependence increased suicide risk

Nicotine Dependence: Increased Suicide Risk

  • Harris et al performed a statistical overview of the medical literature to estimate the suicide risk associated with common mental disorders

  • A standardized mortality ratio (SMR)a was calculated for each disorder

  • Nicotine dependence had a significantly raised SMR, 244 (207-286)

  • There appears to be a distinct association between smoking and suicide

aSMR is an indirect method of adjusting a rate. It is defined as the number of observed deaths (in the cohort) divided by the number of expected deaths. The expected number of deaths in the reference population by age group is applied to the number of persons in each age group in the study population to obtain the expected number of deaths in this population.Harris et al. Br J Psychiatry. 1997;170:205-228; CNN.com. http://archives.cnn.com/2000/HEALTH/children/10/03/teen.smoking.ap. Accessed September 25, 2007.


Smoking suicide connection possible explanations

Smoking–Suicide Connection: Possible Explanations

  • Smoking

    • Is a form of self-medication for depression, a common antecedent of suicide

    • Alters brain chemistry, leading to depression, which increases the risk of suicide

    • Is associated with an increased risk of cancer, which increases the risk of suicide

    • Is associated with other characteristics that predispose individuals to suicide (eg, low self-esteem)

Miller et al. Am J Public Health. 2000;90:768-773.


Summary smoking and suicide

Summary: Smoking and Suicide

  • Positive association between smoking and suicide

  • Smoking is associated with an increased risk of

    • Suicidal behavior among adolescents and adults, independent of other substance use, depressive symptoms, and prior suicidal ideation

    • Both violent and nonviolent suicide

  • Inverse relationship between smoking and indices of serotonin function

  • There are multiple possible explanations for the suicide–smoking connection


Smoking and schizophrenia

Smoking and Schizophrenia


Smoking and schizophrenia1

Smoking and Schizophrenia

  • Among the mentally ill, smoking prevalence is highest in patients with schizophrenia (~70%-90%)

  • Schizophrenic patients smoke at nearly 3 times the rate of the general population

  • Smokers with schizophrenia experience increased

    • Psychiatric symptoms

    • Number of hospitalizations

    • Medication doses

Williams et al. Addict Behav. 2004;29:1067-1083; Dalack et al. Am J Psychiatry. 1998;155:1490-1501; http://www.istockphoto.com/file_closeup/who/character_traits/weakness/2700932_temporary_solution.php?id=2700932. Accessed October 11, 2007.


Financial implications of smoking among schizophrenic patients

Financial Implications of Smoking Among Schizophrenic Patients

  • Smoking imposes a significant financial burden on patients with schizophrenia

Monthly Budget

Cigarettes

Food, Shelter, Other

Steinberg et al. Tob Control. 2004;13:206-208.


Schizophrenia coronary heart disease chd related morbidity

Compared with the general population, patients with schizophrenia

Have a 20% shorter life expectancy

2-fold higher risk of CHD

Twice as likely to die of CHD

Major risk factors for CHD are more common—smoking, hypercholesterolemia, hypertension, obesity, and diabetes

50% to 75% of patients with schizophrenia have CHD

Schizophrenia: Coronary Heart Disease (CHD)-Related Morbidity

CHD=coronary heart disease.

Hennekens et al. Am Heart J. 2005;150:1115-1121; Reader’s Digest Canada. http://www.readersdigest.ca/mag/2002/12/heart_attack.html. Accessed September 25, 2007.


Schizophrenia increased smoking related mortality

Schizophrenia: Increased Smoking-Related Mortality

P=.05

Standardized Mortality Ratio (SMR)a

aStandardized mortality ratio is the number of deaths observed divided by the number of deaths expected and multiplied by 100. An increased SMR is statistically significant when the lower confidence interval (95% CI) is 100 or more.

Brown et al. Br J Psychiartry. 2000;177:212-217.


Increased incidence of smoking in patients with schizophrenia theory

Increased Incidence of Smoking in Patients With Schizophrenia: Theory

  • Psychopathologic basis

    • Schizophrenia is associated with a decrease in dopaminergic activity in the prefrontal cortex

    • Nicotine may reduce negative symptoms in schizophrenia by increasing dopamine release in the prefrontal cortex

  • Pharmacotherapeutic basis

    • Antipsychotic medications block dopamine postsynaptic receptors

    • Schizophrenic patients may smoke to restore these blocked dopamine effects

Schilström et al. Int J Neuropsychopharmacol. 2003;6:1-11.


Smoking and schizophrenia patient perceived benefits

Smoking and Schizophrenia: Patient Perceived Benefits

  • Cigarette smoking in schizophrenia may be reinforcing because it may

    • Improve psychiatric symptoms

    • Improve cognitive functioning

    • Prevent worsening of these symptoms

Williams et al. Addict Behav. 2004;29:1067-1083; http://www.fotosearch.com/IDX015/558904. Accessed October 19, 2007.


Smoking effects of antipsychotic therapy

Smoking: Effects of Antipsychotic Therapy

P=.008

P=.036

CO (ppm)a

Nicotine (ng/mL)b

aCO is expired air carbon monoxide (CO). bNicotine levels were measured by gas chromatography.Patients were prospectively maintained free of antipsychotic medications for 4 to 7 days in hospital before baseline smoking measures were obtained.

McEvoy et al. Psychopharmacology (Berl). 1995;119;124-126.


Smoking effects on drug clearance

Smoking: Effects on Drug Clearance

  • Clearance of psychotropic medications is significantly higher in smokers than in nonsmokers

  • Due to increased clearance, increased dosages often are required to achieve equivalent serum plasma levels

P<.005

16.72

9.99

Clearance (L/min)a

P<.005

7.37

3.16

Fluphenazine

aClearance is directly proportional to the dosing rate divided by the steady-state plasma concentration.

FPZ HCL=fluphenazine hydrochloride; FPZD=fluphenazine decanoate.

Ereshefsky et al. Biol Psychiatry. 1985;20:329-352.


Smoking intervention and schizophrenia

Smoking Intervention and Schizophrenia

  • Underrecognition and undertreatment of nicotine dependence in the schizophrenic population is common

  • Characteristics specific to the disease model and its hospital based treatment may have contributed to the onset and maintenance of nicotine dependence in individuals with schizophrenia

Ziedonis et al. Curr Opin Psychiatry. 2003;16:305-315.


Smoking cessation effects of choice of antipsychotic therapy

Smoking Cessation: Effects of Choice of Antipsychotic Therapy

Patients treated with atypical antipsychotics (n=18)

  • Cessation rates are lower in schizophrenic smokers than in the general population

  • Compared with typical antipsychotic agents, atypical antipsychotic agents (in combination with the nicotine transdermal patch) significantly enhanced the rate of smoking cessation

Patients treated with typical antipsychotics (n=27)

55.6

50

P<.01

Percentage of Patients Who Quit Smoking

22.2

25

P<.02

16.7

7.4

0

End Point

6-MonthFollow-up

George et al. Am J Psychiatry. 2000;157(11):1835-1842.


Summary smoking and schizophrenia

Summary: Smoking and Schizophrenia

  • Among patients with schizophrenia, smoking

    • Is pervasive, affecting 70% to 90% of patients

    • Is underdiagnosed and undertreated

    • Imposes a significant financial burden

    • Contributes to increased incidence of coronary heart disease (CHD)

    • Increases metabolism of psychotropic medications requiring increased dosing

    • May improve psychiatric symptoms, cognitive functioning, and prevent exacerbation of symptomatology

  • Cessation rates are lower in patients with schizophrenia than in the general population


Smoking and anxiety disorder

Smoking and Anxiety Disorder


Anxiety and experimental smoking

Anxiety and Experimental Smoking

  • Anxiety and depressive symptoms, in the presence of peer smoking, predict initiation of experimental smoking

Hazard Ratio (95% CI)a

0-5

6-11

12-17

18+

Levels of Psychiatric Morbidity (CIS Score)b

aThe relative likelihood of experiencing a particular event or the effect of an explanatory variable on the hazard or risk of an event. bClinical Interview Schedule (CIS) is a structured interview designed to assess symptoms of anxiety and depression in nonclinical populations. This scale generates scores (0 to 4) on 14 subscales of common psychiatric symptoms.

Patton et al. Am J Public Health. 1998;88(10):1518-1522.


Adolescent smoking and anxiety disorders

Adolescent Smoking and Anxiety Disorders

120

30

Odds Ratio (95% CI)a,b

20

10

0

Agoraphobia

Generalized Anxiety Disorder

Panic Disorder

aThe ratio of the odds of development of disease in exposed persons to the odds of development of

disease in nonexposed person.bControlling for age, sex, difficult childhood temperament; alcohol and drug use, anxiety, and depressive disorders during adolescence; and parental smoking, education level, and psychopathology.Johnson et al. JAMA. 2000;284:(18):2348-2351.


Nicotine dependence and anxiety

Nicotine Dependence and Anxiety

  • Young adults with nicotine dependence have greater odds of developing anxiety disorder

Odds Ratio (95% CI)a

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for sex and other substance dependencies.

Breslau et al. Behav Genet. 1995;25(2):95-101.


Relationship between anxiety disorder and smoking theory

Relationship Between Anxiety Disorder and Smoking: Theory

  • Anxious individuals are at an elevated risk for nicotine addiction because of:

    • Social factors

      • Peer pressure

      • Social fears

      • Facilitation of social interaction

    • “Calming” effects of smoking

  • Smoking contributes to the development of anxiety disorders because of:

    • Impaired respiration

    • Anxiogenic effects of nicotine

Adapted from:Johnson et al. JAMA. 2000;284(18):2348-2351; http://www.istockphoto.com/file_closeup/

object/3721281_frustration_and_denial.php?id=3721281. Accessed October 11, 2007.


Summary smoking and anxiety disorder

Summary: Smoking and Anxiety Disorder

  • Symptoms of anxiety and depression, in the presence of peer smoking, predict initiation of experimental smoking

  • Nicotine dependence during adolescence is associated with a higher odds ratio of generalized anxiety disorder (GAD) in early adulthood

  • Multiple theories exist about the nature of the relationship between anxiety and smoking


Smoking and panic disorder

Smoking and Panic Disorder


Smoking and panic disorder1

Smoking and Panic Disorder

  • 40% of panic disorder patients smoke

  • Effective substance for self-medication of anxiety

  • Anxiogenic effect of nicotine is hypothesized to be more important in the etiology of panic disorder

  • Positive relationship between smoking and panic disorder

Pohl et al. Psychiatry Res. 1992;43:253-262; Amering et al. Compr Psychiatry. 1999;40(1):35-38; Breslau et al. Arch Gen Psychiatry. 1999;56:1141-1147; Johnson et al. JAMA. 2000;284(18):2348-2351; Isensee. Arch Gen Psychiatry. 2003;60:692-700; Lasser et al. JAMA. 2000;284(20):2606-2610.


Nicotine dependence risk of panic disorder

Nicotine Dependence: Risk of Panic Disorder

P<.05

P<.05

P<.05

Odds Ratio (95% CI)a

Nonsmokers

New Onset of Panic Attacks With Prior Regular Smoking

New Onset of Panic Attacks With Nicotine Dependence

Onset of Panic Disorder With Nicotine Dependence

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.

Isensee et al. Arch Gen Psychiatry. 2003;60:692-700.


Panic disorder increased rates of cessation

Panic Disorder: Increased Rates of Cessation

a

Smokers (%) (95% CI)

a

a

Panic Disorder Patients at Time of Assessment(n=102)

General Population, Aged >15 1991 Census data (N=5,329,300)

Never Smokers

Ex-smokers

Current Smokers

aValue for general population outside CI. bCensus 1991.Amering et al. Compr Psychiatry. 1999;40(1):35-38.


Summary smoking and panic disorder

Summary: Smoking and Panic Disorder

  • Both prior regular smoking and nicotine dependence are associated with risk of anxiety disorders in adolescence and early adulthood

  • Smoking-cessation rates are higher in patients with panic disorder than in the general population


Conclusions

Conclusions

  • Addiction is a multistep process involving multiple neurocircuits

  • Nicotine dependence is an addictive disorder

  • Binding of nicotine to the 42 receptors in the ventral tegmental area (VTA) results in the dopaminergically mediated physical and psychological rewards of smoking

  • Smoking is highly prevalent in the psychiatric population

  • Compared with the general population, schizophrenic and depressed smokers are less likely to successfully quit smoking, although smokers with panic disorder have higher cessation rates

  • Smokers with psychiatric disorders may smoke to ameliorate their pathologic symptomatology

  • There appears to be a distinct association between smoking and suicide

  • Environmental/social stimuli associated with smoking play a role in reinforcing nicotine dependence


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