section 1: burden of disease -...

Tobacco Dependence, Attitudes

and Treatment Strategies

Dr. Vajer Péter

Department of Family Medicine

Semmelweis University

Section 1: Burden of Disease

� Smoking is highly prevalent worldwide

� Smoking increases morbidity and mortality

� The benefits of quitting have been

demonstrated

Gender-Specific Smoking

Prevalence Across the World

1. Mackay J, et al. The Tobacco Atlas. Second Ed. American Cancer Society Myriad Editions Limited, Atlanta,

Georgia, 2006. Also available online at: http://www.myriadeditions.com/statmap/.

US

24%

19%

Men

Women Australia

19%

16%

Belarus

53%

7%

Brazil

22%

14%

Canada

22%

17%

Chile

48%

37%

China

67%

2%

Egypt

45%

12%

France

30%

21%

Iceland

25%

20%

Mexico

13%

5%

Iran

22%

2%

Kenya

21%

1%

Sweden

17%

18%

Philippines

41%

8%

Portugal

33%

10%

South Africa

23%

8%

India

47%

17%

Russian Fed

60%

16%

Italy

33%

17%

Spain

39%

25%

Germany

37%

28%

Smoking Prevalence of Adults vs

Youths: Young People Are Also at Risk

*Young men/women = 15-year-old students who smoke cigarettes.

1. Shafey O, et al (eds). Tobacco Control Country Profiles 2003, American Cancer Society, Atlanta, Georgia, 2003.

Available at: http://www.who.int/tobacco/globaldata/countryprofiles/en/. 2. Mackay J, et al. The Tobacco Atlas. Second

Edition. American Cancer Society Myriad Editions Limited. Atlanta, Georgia, 2006. Also available online at:

http://www.myriadeditions.com/statmap/.

Adults2

Young Men2

Young Women2

1.25 billion smokers worldwide1-2

US

22%

18%

12%

Australia

17%

24%

23%

Belarus

27%

36%

28%

Argentina

29%

16%

28%

Canada

20%

16%

14%

Egypt

29%

6%

3%

France

25%

26%

27%

Ireland

27%

20%

21%

Venezuela

29%

5%

6%

Iran

11%

2%

N/AKenya

11%

8%

4%

Sweden

18%

11%

19%

Philippines

24%

10%

3%

Portugal

21%

18%

26%

South Africa

16%

15%

8%

Russian Fed

35%

27%

19%Spain

32%

24%

32%

Italy

24%

22%

25%

Germany

33%

32%

34%

Smoking: Leading Preventable

Cause of Disease and Death1

Top 3 Smoking-Attributable Causes of Death in US#1 Lung cancer

#2 Ischemic heart disease#3 COPD

Cancer

Lung (#1)* Leukemia

(AML, ALL, CLL)2-4

Oral cavity/pharynx Laryngeal

Esophageal Stomach

Pancreatic Kidney

Bladder Cervical

Cardiovascular

Ischemic heart disease (#2)*

Stroke – Vascular dementia5

Peripheral vascular disease6

Abdominal aortic aneurysm

Respiratory

COPD (#3)*

Pneumonia

Poor asthma control

Reproductive

Low-birth weight

Pregnancy complications

Reduced fertility

Sudden Infant Death Syndrome

Other

Adverse surgical outcomes/wound healing

Hip fractures

Low-bone density

Cataract

Peptic ulcer disease†

*Top 3 smoking-attributable causes of death. †In patients who are Helicobacter pylori positive.

AML = Acute myeloid leukemia; ALL = acute lymphocytic leukemia; CLL = chronic lymphocytic leukemia; COPD =

chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome.

1. Surgeon General’s Report. The Health Consequences of Smoking; 2004. 2. Sandler DP, et al.

J Natl Cancer Inst. 1993;85(24):1994-2003. 3. Crane MM, et al. Cancer Epidemiol Biomarkers Prev. 1996;5(8):639-

644. 4. Miligi L, et al. Am J Ind Med. 1999;36(1):60-69. 5. Roman GC. Cerebrovasc Dis. 2005;20(Suppl 2):91-100. 6.

Willigendael EM, et al. J Vasc Surg. 2004;40:1158-1165.

29%

28%

23%4%

8%

8%

Lung, Trachea, Bronchus Cancer

Ischemic Heart Disease

Respiratory Diseases

Cerebrovascular Disease

Other Cancers

Other Causes

US Mortality From Smoking-Related

Disease*

Approximately 438,000 annual US deaths attributable to cigarette smoking

between 1997 and 2001

†

†

*Percentage of deaths attributable to specific smoking-related diseases, 1997–2001.†Includes secondhand smoke deaths.

1. CDC. MMWR. 2005;54:625–628.

Annual Deaths Attributable to

Tobacco: Worldwide Estimates

Canada

>25%

Australia

20%-24%

UK

>25%

Germany

>25%China & Taiwan

10%-14%

Brazil

15%-19%

% of Total Deaths Attributable to Tobacco*

*Regional estimates in 2000 in men aged >35 years.

1. Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. World Health Organization; 2006.

US

>25%

Mexico

15%-19%

Argentina

15%-19%

Spain

>25%

Russian Federation

>25%Sweden

>25%

Turkey

>25%

% female

deaths

0

• Sub-Saharan

Africa

Four Stages of the Tobacco Epidemic:

Mortality Is Increasing in Many Countries1

If current smoking patterns continue, deaths from smoking in Asia—home to a third of

the world’s population—are expected to increase by 2020 to 4.9 million annually.2

Percentage

of smokers

among adults

Percentage

of deaths

caused by

smoking

• China

• Japan

• Southeast Asia

• Latin America

• North Africa

• Eastern Europe

• Southern Europe

• Western Europe,

UK

• USA

• Canada

• Australia

STAGE 1 STAGE 2 STAGE 3 STAGE 4

70

60

50

40

30

20

10

0

706050403020100 80 90 100

40

30

20

10% male

deaths

% male

smokers% female

smokers

Years

1. Lopez AD, et al. Tobacco Control. 1994;3:242-247. 2. Shafey O, et al (eds). Tobacco Control Country Profiles 2003,

American Cancer Society; 2003; Atlanta, Georgia. Available at:

http://www.who.int/tobacco/global_data/country_profiles/en/. Accessed June 2006.

Results From a Study of Male Physician Smokers in the United Kingdom

1. Doll R, et al. BMJ. 2004;328:1519–1527.

Smoking Reduces Survival an

Average of 10 Years

10 years

24

4

26

59

81

94

100

80

60

40

20

0

40 50 60 70 80 90 100

9791

81

59

2

Age (Years)

Survival At

Each Age

Point (%)

Physician Smokers

Physician Nonsmokers

What’s in a Cigarette?

� Tobacco smoke: ≥4000 chemicals, ≥250 toxic or carcinogenic1

� Nicotine is addictive, but not carcinogenic3

� Smoking cigarettes with lower tar and nicotine provides no health benefit4

Chemical in Tobacco Smoke2 Also Found In…

Acetone Paint stripper

Butane Lighter fluid

Arsenic Ant poison

Cadmium Car batteries

Carbon monoxide Car exhaust fumes

Toluene Industrial solvent

1. National Toxicology Program. 11th Report on Carcinogens; 2005. Available at: http://ntp-server.niehs.nih.gov. 2.

Mackay J, Eriksen M. The Tobacco Atlas. World Health Organization; 2006. 3. Harvard Health Letter. May 2005. 4.

Surgeon General’s Report. The Health Consequences of Smoking; 2004.

Mechanisms of Action:

How Smoking Causes Disease

� Lung cancer

– Direct respiratory cell exposure to potent mutagens

and carcinogens in tobacco smoke

� Ischemic heart disease

– Toxic products in the bloodstream create a

pro-atherogenic environment

– Leads to endothelial injury and dysfunction,

thrombosis, inflammation, and adverse lipid profiles

� Chronic Obstructive Pulmonary Disease (COPD)

– Accelerated decline in respiratory function

1. Surgeon General’s Report. The Health Consequences of Smoking; 2004.

What Does Secondhand Smoke Do?

� Estimated lung cancer risk increased by

20%–30%1

� Believed to cause and worsen diseases such as

asthma, COPD, and emphysema2

� Increases risk for developing heart disease by

25%–30%1

� Increases risk of nonfatal acute myocardial

infarction in a graded manner3

1. News release, June 27, 2006; US Department of Health & Human Services. Available at:

http://www.hhs.gov/news/press/2006pres/20060627.html. 2. Mackay J, et al. The Tobacco Atlas. World Health

Organization; 2002. 3. Teo KK, et al. Lancet. 2006;368:647-658.

What Does Secondhand Smoke Do

to Infants and Children?

� Almost 60% of US children are exposed to secondhand smoke1

� In some countries, ≥80% of youth live in homes where others smoke in their presence2

� Secondhand smoke increases disease burden and hospitalisation in

infants and children. For example:

– UK - 17,000 children under the age of 5 years hospitalised annually3

– Australia - 56% higher risk for hospitalisation if mother smoked in same

room as infant, 73% if smoked while holding infant, and 95% if smoked

while feeding infant (N = 4486)4

– Hong Kong - higher likelihood for hospitalisation for infants living with

any smoker at home with poor smoking hygiene (<3 metres away)5

1. Secondhand smoke; Fact sheet, June 2006. Available at:

http://www.cdc.gov/tobacco/factsheets/secondhand_smoke_factsheet.htm. 2. Mackay J, Eriksen M. The Tobacco

Atlas. World Health Organization; 2006. 3. Fagerstrom K. Drugs. 2002;62(suppl 2):1-9. 4. Blizzard L, et al. Arch

Pediatr Adolesc Med. 2004;158:687-693. 5. Leung GM, et al. Arch Pediatr Adolesc Med. 2004;158:687-693.

Smoking During Pregnancy

Harms Infants

� Exposure during pregnancy associated with1–3

– Increased risk of miscarriage, stillbirth, sudden infant

death syndrome (SIDS); eg

– Low-birth weight

• 4-fold risk1: eg, 9700–18,600 cases related to secondhand

smoke annually in US*3

– Impaired infant lung function2

– Possible association with cognitive and

developmental syndromes1,4

*1990s.

1. Fagerström K. Drugs. 2002;62(Suppl 2):1–9. 2. Le Souef PN. Thorax. 2000;55:1063–1067.

3. Mackay J, et al. The Tobacco Atlas. World Health Organization; 2002. 4. Hellstrom-Lindahl E,

et al. Respiration. 2002;69:289-293.

Importance of NOT Smoking

During Pregnancy

Rate of Infants with Low-Birth Weight

in Taiwanese Infants by Smoking Status of the Mother (N=9499)

†P<0.05 vs never smoked. ‡Before or during first trimester.

1. Wen CP, et al. Tob Control. 2005;14(Suppl 1):i56–i61.

†

†

4.8

5.8

8.2

0

2

4

6

8

10

Rate of Infants With

Low Birth Weight

(%)

Never Smoked Quit Smoking‡ Continued

Smoking

Why Quit? Potential Lifetime Health

Benefits of Quitting Smoking

1. CDC. Surgeon General Report 2004: http://www.cdc.gov/tobacco/sgr/sgr_2004/sgranimation/flash/index.html.

American Cancer Society. Guide to Quitting Smoking. Available at: http://www.cancer.org. Accessed June 2006.

2. American Cancer Society. Guide to Quitting Smoking. Available at: http://www.cancer.org. Accessed June 2006.

3.US Department of Health & Human Services. The Health Benefits of Smoking Cessation: A Report of the Surgeon

General. Centers for Disease Control and Prevention (CDC), Office on Smoking and Health. 1990. Available at:

http://profiles.nlm.nih.gov/NN/B/B/C/T/. Accessed July 2006.

Lung function may start to improve

with decreased cough, sinus

congestion, fatigue, and shortness of

breath

3 months

Lung cancer risk is 30-50% that of continuing smokers

Cessation

CHD: excess risk is reduced by 50% among ex-smokers

Cardiovascular heart disease (CHD) risk is similar to never smokers

Stroke risk returns to the level of people who have never

smoked at 5-15 years post-cessation

1 year

5 years

10 years

15 years

55-64

0

10

20

30

40

50

60

70

80

90

100

40 50 60 70 80 90 100

Age (Years)

1. Doll R, et al. BMJ. 2004;328:1519–1527.

Quitting at Any Age May Increase

Life Expectancy

Stopped Age


Survival At

Each Age

Point (%)

60

Nonsmokers

Cigarette Smokers

0

10

20

30

40

50

60

70

80

90

100

40 50 60 70 80 90 100

1. Doll R, et al. BMJ. 2004;328:1519–1527.


Life Expectancy

Age (Years)

45-54Stopped Age

Nonsmokers

Cigarette Smokers


Survival At

Each Age

Point (%)

50

0

10

20

30

40

50

60

70

80

90

100

40 50 60 70 80 90 100

Age (Years)

1. Doll R, et al. BMJ. 2004;328:1519–1527.


Life Expectancy

� Quitting sooner appears most beneficial

Survival At

Each Age

Point (%)

40

35-44Stopped Age


Nonsmokers

Cigarette Smokers

Risk of Cardiovascular Disease

(CVD) Reduced By Quitting Smoking

� Quitting associated with

– 36% reduction in odds of all-cause mortality among patients with

coronary heart disease (CHD)1

– Decreases in CVD events in cardiac patients, even in those who

recently quit2

*Defined as self-reported smokers who were cotinine negative.

1. Critchley JA, Capewell S. JAMA. 2003;290:86-97. 2. Twardella D et al. Eur Heart J. 2004;25:2101–2108.

0.710.64

0.44

1.00

0.00

0.20

0.40

0.60

0.80

1.00

1.20

Currently Smokes Recently Quit* Formerly

Smoked

Never Smoked

Odds Ratio

Tobacco Dependence

and Treatment Strategies

Mechanism of Action of Nicotine in

the Central Nervous System

� Nicotine binds preferentially to nicotinic acetylcholinergic (nACh) receptors in

the central nervous system; the primary is the αααα4ββββ2 nicotinic receptor in the

Ventral Tegmental Area (VTA)

� After nicotine binds to the αααα4ββββ2 nicotinic receptor in the VTA, it results in a

release of dopamine in the Nucleus Accumbens (nAcc) which is believed to be

linked to reward

αααα4 ββββ2ββββ2ββββ2αααα4

αααα4ββββ2Nicotinic

Receptor

Nicotine Stimulates Dopamine

Release

� Nicotine activates α4β2 nicotinic receptors in the ventral tegmental area resulting in dopamine release at the

nucleus accumbens. This may result in the short-term

reward/satisfaction associated with cigarette smoking.

D

Ventral

Tegmental

Area

Nucleus

Accumbens

Adapted from Picciotto MR, et al. Nicotine and Tob Res. 1999: Suppl 2:S121-S125.

D − α4β2 Nicotinic Receptor− Nicotine − Dopamine

Reward

D

D

D

Axon

1. Schroeder SA. JAMA. 2005;294:482-487. 2. Jarvis MJ. BMJ. 2004; 328:277-279.

Nicotine May Cause Up-Regulation and

Desensitization of Receptors Resulting in

Tolerance

� Tolerance typically develops after long-term nicotine use1

� Tolerance is related to both the up-regulation (increased number)

and the desensitization of nicotine receptors in the VTA1

� A drop in nicotine level, in combination with the up-regulation and

decreased sensitivity of the nicotinic receptor, can result in

withdrawal symptoms and cravings1

� Smokers have the ability to self regulate nicotine intake by the

frequency of cigarette consumption and the intensity of inhalation1

� In order to maintain a steady nicotine level, smokers generally titrate

their smoking to achieve maximal stimulation and avoid symptoms

of withdrawal and craving2

The Cycle of Nicotine Addiction

� Nicotine binding causes an increase in

release of Dopamine1,2

� Dopamine gives feelings of pleasure

and calmness1

� The Dopamine decrease between

cigarettes leads to withdrawal

symptoms of irritability and stress1

� The smoker craves Nicotine to release

more Dopamine to restore pleasure

and calmness1

� Competitive binding of Nicotine to

nicotinic acetylcholinergic receptors

causes prolonged activation,

desensitization, and upregulation2

� As Nicotine levels decrease, receptors

revert to an open state causing

hyperexcitability leading to cravings1,2

1. Jarvis MJ. BMJ. 2004; 328:277-279. 2. Picciotto MR, et al. Nicotine and Tob Res. 1999: Suppl 2:S121-S125.

DopamineDopamine

NicotineNicotine

So Why Do People Smoke?

� Since at least the 1988 Surgeon General’s Report1

– Addiction defined as compulsive use despite damage to the individual or society and drug-seeking behavior can take precedence over important priorities

– Addiction persists despite a desire to quit or even repeated attempts to quit

� Most people smoke primarily because they are addicted to nicotine2

� There is a clear link between smoking, nicotinic receptors, and addiction21. Centers for Disease Control and Prevention. The Health Consequences of Smoking: Nicotine Addiction; A

Report of the Surgeon General. Washington DC: US Department of Health and Human Services; 1988.

2. Jarvis MJ. BMJ. 2004;328:277-279.

AddictionAddiction –– Habitual psychological and physiological dependence Habitual psychological and physiological dependence

on substance or practice which is beyond voluntary controlon substance or practice which is beyond voluntary control

–– StedmanStedman’’s Medical Dictionarys Medical Dictionary

Nicotine Addiction: A Chronic

Relapsing Medical Condition

� True drug addiction1

� Requires long-term clinical intervention, as do other addictive

disorders

– Failure to appreciate the chronic nature of nicotine addiction

may2

• Impair clinicians’ motivation to treat tobacco dependence long-term

• Impede acceptance that condition is comparable to diabetes,

hypertension, or hyperlipidemia, and requires counseling, support, and

appropriate pharmacotherapy

� Relapse is

– Common1,2

– The nature of addiction, not the failure of the individual3

• Long-term smoking abstinence in those who try to quit unaided† = 3%–5%

• Most relapse within the first 8 days

1. Fiore MC, Bailey WC, Cohen SJ, et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence. US

Department of Health and Human Services. Public Health Service; June 2000. Available at:

www.surgeongeneral.gov/tobacco/default.htm. 2. Jarvis MJ. Why people smoke. BMJ. 2004;328:277-279.

Tobacco Dependence and Environmental

Behavior Reinforcement

� Pharmacologic effects

– Nicotine is a primary reinforcer

� Non-pharmacologic effects

– Environmental/social stimuli associated with smoking

play a role in reinforcing nicotine dependence

– Environmental/social stimuli enhance the reinforcing

effects of nicotine

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

1. Caggiula AR et al. Psychol Behavior. 2002;77:683–687.

Withdrawal Syndrome: a Combination of Physical and Psychological Conditions, Making

Smoking Hard to Treat1,2

Restlessness or impatience

(<4 weeks)2

Increased appetite or weight gain(>10 weeks)2

Withdrawal Syndrome

Anxiety(may increase or

decrease with quitting)1,2

Dysphoric or depressed mood

(<4 weeks)2

Irritability, frustration, or anger

(<4 weeks)2

Difficulty concentrating(<4 weeks)2

Insomnia/sleep disturbance(<4 weeks)2

1. Diagnostic and Statistical Manual of Mental Disorders, IV-TR. Washington, DC: APA; 2006: Available at

http://psychiatryonline.com. Accessed November 7, 2006. 2. West RW, et al. Fast Facts: Smoking Cessation. 1st ed.

Oxford, United Kingdom. Health Press Limited. 2004.

Why Some Smokers May Need More

Help to Quit

� Studies show some groups may be less

likely to quit:

– Higher level of dependence1

• Cigarettes per day

• Time to first cigarette upon awakening

– Living with a current smoker1

– Fewer educational qualifications2

– Lower socioeconomic class2

– Co-morbid psychiatric disorders3

1. Hyland A et al. Nicotine Tob Res. 2004;6(Suppl 3):S363-S369. 2. Chandola T et al. Addiction. 2004;99:770-777.

3. Kalman D et al. Am J Addict. 2005;14:106–123.

Multiple Quit Attempts

May Be Necessary

� More than 70% of US smokers have attempted to quit1

– Approximately 46% try to quit each year

– Less than 5% who try to quit are abstinent 1 year later

– Similar percentages in countries with established tobacco control

programs (eg, Australia, Canada, UK)2

• 30% to 50% try to quit; <5% achieve long-term abstinence

� Some smokers succeed after making several attempts3

– Past failure does not prevent future success

– Length of prior abstinence is related to quitting success

1. Fiore MC, et al. US Department of Health and Human Services. Public Health Service. June 2000. 2. Foulds J, et

al. Expert Opin Emerg Drugs. 2004;9:39–53. 3. Grandes G, et al. Br J Gen Pract. 2003;53:101–107.

Most Smokers Are Willing to

Try Again

� Of smokers who relapsed following a quit

attempt:

– 98% were willing to try again

– 50% immediately

– 28% within 1 month

� Of those willing to try again immediately

– Percentage did not differ based on time since

previous attempt

� Some smokers may prefer a waiting period

before attempting to quit again

1. Joseph A, et al. Nicotine Tob Res. 2004;6:1075–1077.

Length of Prior Abstinence Is

Related to Quitting Success

� Previous quit attempts of ≥3 months

positively predicted sustained,

biochemically confirmed abstinence1

– N = 1768; OR* = 1.8; 95% CI = 1.1–2.7

� Duration of previous quit attempts

influenced continuous abstinence at 6

months2

– N = 509; OR* = 1.73; 95% CI = 1.09–2.75

*OR = odds ratio.

1. Grandes G et al. Br J Gen Pract. 2003;53:101–107. 2. Aubin HJ et al. Addiction. 2004;99:1206-1218.

Non-pharmacologic Therapies:

Advice and Support

� All smokers should be1

– Advised to quit (the “5As”)

– Offered assistance irrespective of motivation

� Three types of non-pharmacologic therapies are

effective1

– Practical counseling (problem solving/skills training)

– Social support as part of treatment

– Securing social support outside of treatment

� Effectiveness increases with treatment intensity1,2

1. Fiore MC, et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence. US Department of Health

and Human Services. Public Health Service; June 2000. Available at:

www.surgeongeneral.gov/tobacco/default.htm.

2. National Institute for Health and Clinical Excellence. Brief interventions and referral for smoking cessation in

primary care. Available at: www.nice.org.uk/page.aspx?o=299611. Accessed September 2006.

Tobacco Dependence Support:

The “5As”

� Ask about tobacco use

� Advise to quit

� Assess willingness to make a quit attempt

� Assist in quit attempt

� Arrange follow-up

1. Fiore MC, et al. US Department of Health and Human Services. Public Health Service. June 2000.

The “5As”: Ask About Tobacco Use

� Identify and document tobacco use status for

every patient at every visit

� Implement an office-wide system that ensures

tobacco-use status is queried and documented

– Expand vital sign documentation to include tobacco

use

– Tobacco-use stickers on charts

– Computer reminder systems for electronic medical

records


The “5As”: Advise to Quit

� In a clear, strong, and personalized manner, urge every

tobacco user to quit at least once per year

– CLEAR

• “I think it is important for you to quit smoking now, and I can help

you.”

– STRONG

• “As your clinician, I need you to know that quitting smoking is very

important to protecting your health now and in the future.”

– PERSONALIZED

• Tie tobacco use to health/illness (reason for office visit),

social/economic costs, motivation level, and impact on others

(children)


The “5As”: Assess Willingness to

Make a Quit Attempt

� Is the tobacco user willing to make a quit attempt

at this time?

– If patient is willing to attempt quitting, offer assistance

– If patient is unwilling to quit now, provide motivational

intervention


The “5As”: Assist in Quit Attempt

� For the patient willing to make a quit attempt, use

counseling and pharmacotherapy

– Provide practical counseling (problem solving and skills training)

– Provide social support

– Offer pharmacotherapy as appropriate

– Provide supplementary materials

• World Health Organization: www.who.int

• Centers for Disease Control and Prevention: www.cdc.gov/tobacco

• Society for Research on Nicotine and Tobacco: www.srnt.org

– Consider need for referral to formal program

• In person

• Telephone or internet-based


The “5As”: Arrange Follow-up

� Schedule follow-up contact, preferably within the first

week after the quit date

� Follow-up can occur either in person or via telephone

� Follow-up actions

– Congratulate success

– Review circumstances of lapse – elicit recommitment to

abstinence

– Identify and anticipate challenges

– Assess pharmacotherapy use

– Consider referral for more intensive treatment


Patient Satisfaction Linked With

“5A” Interventions

� Regardless of readiness to quit, smokers receiving 5A

interventions were more satisfied with their health care

N=1160.

*P<0.0001; †P= 0.0014.

1. Conroy MB, et al. Nicotine Tob Research 2005;7(Suppl 1):S29–S34.

*

†

†

†

†

0 20 40 60 80 100

Arranged

Assisted

Assessed

Advised

Asked

Very Satisfied (%)

Received 5As

No 5As

Effectiveness Increases with

Treatment Intensity

Level of Contact

Estimated Odds

Ratio

(95% CI)

Estimated

Abstinence Rate

(95% CI)

No Contact 1.0 10.9

Minimal Counseling

(less than 3 minutes)1.3 (1.01, 1.6) 13.4 (10.9, 16.1)

Low Intensity Counseling

(3 to 10 minutes)1.6 (1.2, 2.0) 16.0 (12.8, 19.2)

Higher Intensity Counseling

(more than 10 minutes)2.3 (2.0, 2.7) 22.1 (19.4, 24.7)

1. Fiore MC, et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence. US Department of Health and

Human Services. Public Health Service; June 2000. Available at: www.surgeongeneral.gov/tobacco/default.htm.

Non-Pharmacologic Treatment

for Smoking Cessation

Comparison

N

Trials

N

Participants

Pooled OR*

(95% CI)

Physician advice1

Brief vs no advice (usual care)

Intensive vs minimal advice

17

15

>13,000

>9,000

1.74 (1.48–2.05)

1.44 (1.24–1.67)

Individual counseling2

Vs minimal behavior intervention 17 >6,000 1.56 (1.32–1.84)

Group counseling3

Vs self-help

Vs no intervention

16

7

>4,000

815

2.04 (1.60–2.60)

2.17 (1.37–3.45)

Proactive Telephone counseling4

Vs less intensive interventions 13 >16,000 1.56 (1.38–1.77)

Self-help5

Vs no intervention 11 >13,000 1.24 (1.07–1.45)

*Abstinence assessed at least 6-months following intervention.

1. Lancaster T, Stead LF. Cochrane Database Syst Rev. 2004;(4):CD000165. 2. Lancaster T, Stead LF. Cochrane

Database Syst Rev. 2005;(2):CD001292. 3. Stead LF, Lancaster T. Cochrane Database Syst Rev. 2005;(4):

CD001007. 4. Stead LF et al. Cochrane Database Syst Rev. 2005;(4):CD002850. 5. Lancaster T, Stead LF. Cochrane

Database Syst Rev. 2005;(3):CD001118.

Pharmacotherapy for Tobacco

Dependence

� Nicotine replacement therapy (NRT)1

– Long acting1-3

• Patch

– Short acting1-3

• Gum

• Inhaler

• Nasal spray

• Sublingual tablets/lozenges

� Antidepressants4

– Bupropion SR4

– Nortriptyline3 (not approved for smoking cessation)

� Varenicline

1. Silagy C, et al. Cochrane Database Syst Rev. 2004;(3):CD000146. 2. Stead L, et al. Int J Epidemiol.

2005;34:1001–1003. 3. Henningfield JE, et al. CA Cancer J Clin. 2005;55:281-299.

4. Hughes JR et al. Cochrane Database Syst Rev. 2004;(4):CD000031.

Nicotine Replacement Therapy (NRT)

� Indication

– NRT has been shown to be safe and effective in

helping people stop using cigarettes when used as

part of a comprehensive smoking cessation program1

� Delivers nicotine that binds to the nAChR

receptors1

� Does not generally counter the additional

satisfaction from smoking1

� NRTs may not deliver nicotine to the circulation

as fast as smoking2

1. American Heart Association website: http://www.americanheart.org/presenter.jhtml?identifier=4615, accessed

November 5, 2006. 2. Sweeney CT, et al. CNS Drugs. 2001;15:453-467.

0

2

4

6

8

10

12

14

16

18

0 10 20 30 40 50 60 70 80 90 100 110 120

Nicotine Replacement Therapy (NRT): Nicotine

Delivery by Cigarettes and NRT Products

Cigarette (nicotine delivery, 1-2 mg)

Gum (nicotine delivery, 4 mg)

Nasal spray (nicotine delivery, 1 mg)

Transdermal patch

Time post-administration (minutes)

Plasma

Nicotine

Concentration (µg/L)

1. Sweeney CT, et al. CNS Drugs. 2001;15:453-467.

Efficacy of Nicotine Replacement

Therapy (NRT)1,2

Comparison

N

Trials

N

Participants

Pooled OR

(95% CI)

Gum 52 17,783 1.66 (1.52–1.81)

Patch 37 16,691 1.81 (1.63–2.02)

Nasal spray 4 887 2.35 (1.63–3.38)

Inhaler 4 976 2.14 (1.44–3.18)

Tablets/lozenges 4 2739 2.05 (1.62–2.59)

Combination vs single type 7 3202 1.42 (1.14–1.76)

Any NRT vs control 103 39,503 1.77 (1.66–1.88)

1. Silagy C et al. Cochrane Database Syst Rev. 2004;(3):CD000146. 2. Stead L, Lancaster T. Int J Epidemiol.

2005;34:1001–1003.

Bupropion SR (Zyban®)

� ZYBAN (bupropion SR hydrochloride) is a non-nicotine sustained-release tablet for smoking cessation

� Initially developed as an antidepressant, later found to have efficacy in smoking cessation1

� There are 2 potential MOAs:– Blocks reuptake of dopamine2,3

– Non-competitive inhibition of α3β2 and α4β2 nicotine receptors4,5

1. Package Insert. bupropion SR hydrocloride [Zyban®]. GlaxoSmithKline. 2. Henningfield JE, et al. CA Cancer J Clin.

2005;55:281–299. 3. Foulds J, et al. Expert Opin Emerg Drugs. 2004;9:39–53. 4. Slemmer JE, et al. J Pharmacol

Exp Ther. 2000;295:321–327. 5. Roddy E. Br Med J. 2004;328:509–511.

Comparison of Nicotine Replacement Therapy (NRT)

and Bupropion SR Therapy for Quitting Smoking1

� Only study comparing NRT and antidepressant

therapy for quitting smoking2

*P≤ 0.001 vs placebo and patch alone.

1. Jorenby DE, et al. N Engl J Med. 1999;340:685–691. 2. Talwar A et al. Med Clin North Am. 2004;88:1517–1534.

5.69.8

18.4*22.5*

0

10

20

30

40

50

1 Year Continuous Abstinence(Week 2 to Week 52)

Abstinence

Rate (%)

Placebo (n = 160) Nicotine Patch (n = 244)

Bupropion SR (n = 244) Bupropion SR + Patch (n = 245)

Champix (varenicline): A Highly

Selective αααα4ββββ2 Receptor Partial Agonist

1. Coe JW et al. Presented at the 11th Annual Meeting and 7th European Conference of the Society for Research on

Nicotine and Tobacco. 2005. Prague, Czech Republic. 2. Picciotto MR et al. Nicotine Tob Res. 1999; Suppl 2:S121-

S125.

Binding of nicotine at the α4β2 nicotinic receptor in the VTA is believed to cause release of dopamine at the nAcc

Champix is an α4β2 nicotinic receptor partial agonist, a compound with dual agonist and antagonist activities. This is believed to result in both a lesser amount of dopamine release from the VTA at the nAcc as well as the prevention of nicotine binding at the α4β2 receptors.

Nicotine Chantix

Varenicline Mechanism of Action:

Efficacy for Tobacco Dependence

� Efficacy of varenicline in tobacco dependence – Believed to result from partial agonist activity at the α4β2

nicotinic receptor

� By preventing binding of nicotine, varenicline– Reduces craving and withdrawal symptoms (agonist activity)

– Produces a reduction of the rewarding and reinforcing effects ofsmoking (antagonist activity)

� The most frequently reported adverse events (>10%) with varenicline were nausea, headache, insomnia, and abnormal dreams.

1. Champix Summary of Product Characteristics. Pfizer Ltd, Sandwich, UK. 2006.

1: Findings from the STOP survey

69

81

97

92

87

53

0 20 40 60 80 100

Smoking is a lifestyle choice

Smoking is a medical condition

Smoking is addictive

Stopping is primarily down to willpower

Helping patient stop is part of job

Other things have higher priority

Percent

Pfizer-sponsored survey: Interviews with 2836 smoking and non-smoking

general practitioners in 16 countries

1: Apparent paradoxes

Smoking is an addiction stopping is a matter of

willpower

Smoking should be

regarded as a medical

condition

is primarily a lifestyle

choice

Helping patients to stop

is part of the job

other things have a

higher priority

but

1: What does this mean?

Need a message that recognises the

duality of beliefs about smoking

“Smokers must take responsibility for

stopping smoking, and they will need

determination to succeed; but when

determination is not enough, the

physician has effective tools to help the

smoker succeed.”

2: A simple model of nicotine

dependence

Chronic intake of

nicotine from

cigarettes

Changes to the

neural circuits

controlling

motivation

Nicotine hunger Nicotine habit False beliefs

A biologically driven

“need” to smoke

when nicotine levels

in the brain are low

Cues associated with

smoking trigger

nicotine-driven

reward seeking

Experience of relief

of nicotine withdrawal

symptoms leads to

expectations of more

general mood

enhancement

2: The process of stopping

Motivational tension

Triggers

Treatment

When smokers think about their smoking

most, they are unhappy about it, but many

of them:

Something needs to prompt them to make a

quit attempt using a method that maximises

their chances of success

The treatment needs to be of a type and

intensity that meets the individual smoker’s

needs, and available whenever and for as

long as the smoker needs it

1. Think it meets certain needs

2. Is a source of enjoyment

3. Think stopping will be difficult

3: The physician’s role

The

physician’s

role is:

Patients will

often respond

to a clear, firm

message from

their doctor

that:

• To give professional, expert

advice on health matters

• To provide treatment to those

who want and need it

• Now is a good time to stop

• It is always worth having

another attempt

• There are things available that

will make it easier

3: A simple consultation model

Yes, I know I should

stop, but...

I enjoy smoking

too much

Every month you put off

stopping, you may lose another

week off your life

Now is not a good time Now is always a good time for

stopping, smoking doesn’t really

help with stress

I am worried that

I will fail

Most smokers make many

attempts before they succeed

I am addicted Addictions can be conquered,

especially when you get help

We now

have

effective

treatments

available

that will

make it a lot

easier for

you to

succeed

Are you

smoking

at the

moment?

You have to question whether it is

worth the pain and suffering

you will endure later

It’s never too late…

section 1: burden of disease -...

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