Smoking Cessation

Gamal Rabie Agmy ,MD ,FCCP Professor of Chest Diseases, Assiut University

Facts about SmokingMost of those killed by tobacco are not particularly heavy

smokers and most started as teenagers.Approximately 50 percent of smokers die prematurely

from their smoking, on average 14 years earlier than non-smokers.

Smoking kills one in two of those who continue to smoke past age 35.

There is evidence that smoking can cause about 40 different diseases.

the preventable mortality attributed to smoking is 8 percent of deaths in females and 19 percent in males.

Smoking is socioeconomically patterned with higher rates of smoking in lower socio-economic groups. Thus tobacco

smoking produces a greater relative burden of disease and premature death in lower socioeconomic groups and is a

major contributor to socioeconomic inequalities in health.

Facts (cont.)Smoking, especially current smoking, is a crucial

and extremely modifiable independent determinant of stroke.

Second-hand smoke (also called environmental tobacco smoke) is a Class A carcinogen and

contains approximately 4,000 chemicals.Exposure of children to second-hand smoke:

▫ can cause middle ear effusion▫ increases the risk of croup, pneumonia and bronchiolitis

by 60 percent in the first 18 months of life▫ increases the frequency and severity of asthma episodes▫ is a risk factor for induction of asthma in asymptomatic

children.

Benefits of Smoking CessationThese points may be helpful in motivating people to quit smoking. Many smokers deny being at increased risk of cancer and heart disease and more accurate perception of risk may assist cessation efforts.

It is beneficial to stop smoking at any age. The earlier smoking is stopped, the greater the health gain.

Smoking cessation has major and immediate health benefits for smokers of all ages. Former smokers have fewer days of illness, fewer health complaints, and view themselves as healthier.

Within one day of quitting, the chance of a heart attack decreases.

Within two days of quitting, smell and taste are enhanced.Within two weeks to three months of quitting, circulation

improves and lung function increases by up to 30 percent.

Excess risk of heart disease is reduced by half after one year’s abstinence. The risk of a major coronary event reduces to the level of a never smoker within

five years. In those with existing heart disease, cessation reduces the risk of recurrent infarction

or death by half.

Former smokers live longer: after 10 to 15 years’ abstinence, the risk of dying almost returns to that of people who never smoked. Smoking cessation at all ages, including in older people, reduces risk of

premature death.

Men who smoke are 17 times more likely than non-smokers to develop lung cancer. After 10 years’

abstinence, former smokers’ risk is only 30 to 50 percent that of continuing smokers, and continues

to decline.

Women who stop smoking before or during the first trimester of pregnancy

reduce risks to their baby to a level comparable to that of women who have

never smoked. Around one in four low birth weight infants could be prevented

by eliminating smoking during pregnancy.

The average weight gain of three kg and the adverse temporary psychological

effects of quitting are far outweighed by the health benefits.

Evidence for Effectiveness of Health Professional InterventionA Cochrane review of 16 RCTs found simple advice from

doctors had a significant effect on cessation rates (OR for quitting 1.69; 95% confidence interval 1.45–1.98).

When trained providers are routinely prompted to intervene with people who smoke, they achieve significant reductions in smoking prevalence (up to 15 percent cessation rates compared with 5 to 10 percent in non-intervention sites).

Doctors and other health professionals using multiple types of intervention to deliver individualized advice on multiple occasions produce the best results. Frequent and consistent interventions over time are more important than the type of intervention.

Smoking Cessation Program

The only way any country can substantially reduce smoking and other tobacco use within its borders is to establish a well-funded and sustained comprehensive tobacco prevention program that employs a variety of effective approaches.

Nothing else will successfully compete against the addictive power of nicotine and the tobacco industry's aggressive marketing tactics.

ESSENTIAL COMPONENTS

The following elements must all be included to maximize the success of any program to reduce

tobacco use. Conducted in isolation, each of these elements can reduce tobacco use, but done

together they have a much more powerful impact:

Public Education Efforts Community-Based ProgramsHelping Smokers Quit (Cessation)School-Based ProgramsEnforcementMonitoring and EvaluationRelated Policy Efforts

Guidelines forIndividual Smoking

Cessation

Tobacco dependence is a chronic condition that often requires repeated intervention. However, effective treatments exist that can produce long-term abstinence.

These guidelines are designed for smoking cessation providers to assist all clients with smoking cessation.

Promoting Smoking CessationTHE FIVE A’S: ASK

ASSESS ADVISE ASSIST

ARRANGE

ASK

ASSESS

Ask

ADVISE

ASSIST

Ranking of nicotine in relation to other drugs in terms of addiction

Dependence among users

nicotine>heroin>cocaine>alcohol>caffeine

Difficulty achieving abstinence

(alcohol=cocaine=heroin=nicotine)>caffeine

Tolerance (alcohol=heroin=nicotine)>cocaine>caffeine

Physical withdrawal severity

alcohol>heroin>nicotine>cocaine>caffeine

Deaths nicotine>alcohol>(cocaine=heroin)>caffeine

Importance in user's daily life

(alcohol=cocaine=heroin=nicotine)>caffeine

Prevalence caffeine>nicotine>alcohol>(cocaine=heroin)

27

Tobacco Effects on Psychiatric Medication Blood Levels

Smoking induces the P450’s 1A2 isoenzyme secondary to the polynuclear aromatic hydrocarbons

Smoking increases the metabolism of some medications

– Haldol, Prolixin, Olanzapine, Clozapine, Mellaril, Thorazine, etc Caffeine is metabolized through 1A2 CHECK for medication SE or relapse to mental

illness with changes in smoking status Nicotine does not change medication blood levels

(2D6) NRT doesn’t affect medication blood levels Nicotine may modulate cognition, psychiatric

symptoms, and medication side effects 28

Nicotine Replacement Therapy (NRT) -Patch (OTC) -Gum (OTC) -Lozenge (OTC) -Oral Inhaler (Rx) -Nasal Spray (Rx) Non-Nicotine Medications -Varenicline (Chantix, Rx) -Bupropion Hydrochloride (Rx)

First-Line Medications

29

30

Reasons for Using NRTIt works: roughly doubling success

rates.It helps the person feel more

comfortable (treats nicotine withdrawal syndrome).

It is very safe: the person is getting “clean” nicotine instead of “dirty”

nicotine with 4000 plus chemicals.31

Nicotine withdrawal Withdrawal syndrome is

a collection of signs and symptoms caused by

abstinence

Nicotine or cigarette withdrawal?

Nicotine replacement reduces severity of

withdrawal symptoms

32

Sign of Nicotine Toxicity

• Extremely RARE IN SMOKERS & thus even more rare in NRT use.

• Nausea and/or vomiting• Sweating

• Vertigo and/or Light-headedness• Tremors

• Confusion• Weakness

• Racing heart

33

Nicotine Patch Dosing:

< 10 cigs/day: 14 mg patch

≥ 10 cigs/day: 21 mg patch

Length of Treatment:

Up to 12 weeks (PDR)Use: Apply to clean skin area(upper trunk/ arms)24 or 16 hour dosing, try24 to dec. morning cravingWatch for nightmaresGiven with or without taper

34

Pros: -Easy, good compliance -Continuous nicotine delivery-OTCCons: -Slow onset of action -Skin reaction, Insomnia

Nicotine Gum

Dosing:

2mg < 25 cigarettes/day

4mg > 25 cigarettes/day Length of Treatment:

8-10 weeks (PDR)

35

Use: Chew and park (oral absorption) Slow, buccal absorption Acidic foods ↓ absorptionPros: Flexible dosing (every 1-2 hours, up to 24 pieces/day) Keeps mouth busy OTCCons: Need to use correctly (chew and park) Nausea, Heartburn Mouth and throat burning

36

Nicotine Lozenge

Use: Allow to dissolve (Don’t Chew but Suck like a hard candy.)

Pros: Flexible dosing (Up to 20 lozenges/ day) More discreet than gum; Keep mouth busy; OTC;

Cons: Need to use correctly (don’t chew, suck) May cause insomnia, some nausea, hiccups, heartburn, coughing

Dosing: Based on Time To First Cigarette (TTFC) 4 mg ≤ if 30 mins TTFC 2mg > if 30 mins TTFC

37

Length of Treatment: 12 weeks (PDR)

Nicotine Nasal SprayDosing: 1-2 doses per hour

1 does = 2 spays (1 spray/nostril)

Use enough to control withdrawal symptoms

Length of Treatment:

3-6 months weeks (PDR)

38

Nicotine Nasal Spray Use: Spray (don’t sniff, swallow, or inhale)

PRN or fixed-schedule (1-2 doses/hour) Pros: Rapid delivery though nasal mucosa

Flexible dosing (up to 40 doses) Cons: Nasal irritation, rhinitis, coughing, &

watering eyes.

Some dependence liability

Rx needed

39

Nicotine MedicationsUse high enough doseScheduled better than PRN Use long enough time periodCan be combined with BupropionDon’t combine with VareniclineCan be combined with eachotherHave very few contraindicationsHave no drug-drug interactions

40

Efficacy of NRT medications

1.73 1.66 1.76 2.082.27

0

0.5

1

1.5

2

2.5

Odds Ratio of 6 month abstinence

Overall Gum Patch Inhaler Nasal spray

41

Withdrawal Symptoms and NRT

0

50

100

150

200

Tot

al W

ithd

raw

al

Sm

okin

g

Com

bo

Pat

c h

Gum

Pla

cebo

N.S.

N.S. **

* *** N.S.

*** *** *** ***

Total withdrawal in mm (calculated by averaging each symptom over the 11 ratings and adding the 9 symptoms) for the 4 treatments and baseline smoking with P-values adjusted for multiple testing (Bonferoni correction).

* P < 0.05

** P < 0.01

*** P < 0.001

Adapted from: Fagerström et. al. Psychopharmacology, 1993, 111:3, 271-7

42

Some strategies Recommended doses of nicotine replacement therapy are

inadequate for many smokers In heavy smokers, under dosing may limit the

effectiveness of patch Patch plus Gum

– Improves abstinence rates (Kornitzer 1995, Puska 1995)

– Decreased withdrawal (Fagerstrom 1993)– Well tolerated

UMass uses up to 42mg patch or patch plus GUM

43

Odds Ratios for the Efficacy of Higher Doses and NRT

Combinations

Gum (4mg vs 2 mg)

Patch (21mg vs 14)

Comb vs single ttt

Comb vs patch only

1.98 (1.30-3.00)

1.27 (1.03-1.57)

1.64 (1.22-2.21)

1.87 (1.17-2.99)

44

Smoking with NRT

Relatively safe Harm ReductionLess reinforcing effectsNot a distraction from quit

attempts(Benowitz 1997, Hartman 1991, Slade 1995)

45

Concern about this is not supported by data. Joseph took a high risk cardiac group and put them

on patch or placebo.– 49% with active angina– 40% with history of heart attack– 35% with history of cardiac bypass– No increase in cardiac events for the patient group– 21% of the patients were not smoking at the end vs 9% of the

placebo group. – Jiminez-Ruiz put severe COPD patients on nicotine gum – Most patients continued to smoke, though less.– No adverse events attributed to nicotine.– COPD (chronic obstructive pulmonary disease) got better

(Joseph AM. NEJM 335:1792-8, 1996 & Jiminez-Ruiz. Respiration 69:452-6, 2002)Slide copied from OASAS.

Smoking and NRT: IS THAT SAFE?

46

Conclusions

Nicotine Replacement Therapy is being provided to assist tobacco users to

become tobacco free. NRT is not a treatment in itself, but is

intended to complement the other assessments and treatments provided. NRT works by reducing craving and

withdrawal severity, enabling the patient to feel comfortable and able to

concentrate on other psychosocial treatments.

47

Non-Nicotine Pharmacotherapy

First-line non-nicotine medications

-Bupropion (Zyban/Wellbutrin)**

-Varenicline (Chantix)**Others (nortriptyline, clonidine)

**FDA Approved for smoking cessation

48

Bupropion Hydrochloride

Dopamine and norepinephrine (noradrenaline) effects

Reduces cravings, withdrawal Improved abstinence rates in trials Less weight gain while using (Need to gain

100 pounds to diminish health benefit) Start 7-10 days prior to quit date Continue 7-12 weeks or longer ( > 6

months)

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Bupropion Precautions

Contraindicated: seizure disorder, eating disorders, electrolyte abnormalities, MAO use

– OK with SSRIs

NOT dangerous to smoke while taking Monitor blood pressure Side effects:

– Insomnia (40%) 2nd dose early evening helps

– Dry mouth– Headaches– Rash

50

Bupropion Efficacy

0

10

20

30

40

50

7 week abstinence 1 year abstinence

Placebo

100 mg

150 mg

300 mg

**

* *

Hurt, 199751

Varenicline (Chantix)

Action at 42 nicotine receptor

Partial agonist/antagonist Releases lower amounts of dopamine

into brain than smoke– Reduces withdrawal– Not as addictive as smoke

Blocks nicotine from binding to receptor– Prevents reward of smoking

Varenicline (Chantix)

Action at 42 nicotine receptor

Partial agonist/antagonist Releases lower amounts of dopamine

into brain than smoke– Reduces withdrawal– Not as addictive as smoke

Blocks nicotine from binding to receptor– Prevents reward of smoking

53

Dosing Titrate dose from 0.5

mg daily to twice daily to 1 mg twice daily over 1 week

Abstinence rates better vs. placebo and Bupropion at 1 year

Optimal duration 12-24 weeks

Most common side effect is nausea

CHX 0.5Pfizer

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Abstinence by medication use

31%

52%

64%74%

82%

42%42%37%37%

20%

0%

20%

40%

60%

80%

100%

No meds 1 med 2 meds 3 meds 4+ meds

4-week abstinence 6-month abstinence

55

Serious Mental Illness

Reduced Cessation

-Schizophrenia/Schizoaffective disorder

-Bipolar disorder

-PTSD

-Alcohol use disorder

56

Smoking and SchizophreniaHigh prevalence of smoking (about

90%, OR = 5.9)Highly nicotine dependent (FTND = 7

or higher)Nicotine produces cognitive or other

benefitSmoking ameliorates medication side

effects (e.g., lower rates of neuroleptic-induced Parkinsonism)

57

Smoking and Schizophrenia (Continued)

Smokers with schizophrenia take in more nicotine per cigarette than smokers without this disorder

Higher levels of positive symptoms and decreased negative symptoms

Ad libitum smoking increases after initiation of haloperidol

SCZ tend to smoke less on clozapine

58

Neurobiology of Smoking and Schizophrenia

Decreased low affinity and high affinity nAChRs

Abnormal P50 responses are normalized

Improved Spontaneous Pursuit Eye Movement and decreased Saccades with nicotine

Improved cognition and attention

59

Smoking & Bipolar DisorderHigh prevalence of smoking: 61-80% Findings are inconsistent regarding

the prevalence of smoking between bipolar disorder with and without psychotic features

Bupropion is contraindicated Quit rates are comparable to general

population and durableQuit rates enhanced with CBT

60

Smoking and Depression The prevalence of smoking: 37-60% Leads to more severe nicotine withdrawal

symptoms - High risk for relapse in first week - Female > Male

30% risk of relapse to MDE after quitting if past history present

Depressed smokers have higher suicide rates than depressed nonsmokers

(Bruce, 1994; Lohr, 1992; Yassa, 1987)

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Link Between MDD and Smoking

0

10

20

30

40

50

60

Lifetime Prevalence of

Major Depression (%)

None 1 to 5 6 to 10 11 to 20 >21

Average Daily Cigarette Consumption

Adapted from Kendler KS, 199362

Smoking and Depression (Continued)

NRT alone insufficient treatment for smokers with current and/or past MDD

Combining NRT with non-NRT pharmacotherapy appear to be promising

for smokers with depression (Ait-Daoud et al., 2006)

CBT that emphasizes group cohesion and social support appears to be

particularly effective for depressed smokers with or without alcohol

dependence 63

Smoking and Anxiety D/O The prevalence of smoking: About 35-50%

Smokers have greater anxiety and panic symptoms than non-smokers

Heavy smoking in adolescent is associated with higher risk of developing Agoraphobia, GAD, and Panic

Disorder PTSD:

– Increased risk for relapse in first two weeks of quit attempt– Increased the risk of smoking and nicotine dependence

– lower rates for quitting smoking & remission from nicotine dependence– Stopping smoking not associated with worsening of PTSD

– Bupropion tolerated and effective treatment

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SSRIs and Smokers with Anxiety Disorder

No benefit for smoking cessationCan reduce likelihood of emergent anxiety

and panic during quit attempt Bupropion is not appropriate as only

medication Can be combined with NRT/Bupuropion

Can be combined with varnicline

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Smoking and Alcohol DependenceHigh prevalence of smoking: 80-95% Two studies reporting similar outcomes of

NRT in alcoholics compared with non-alcoholics (e.g., Grant et al., Alcohol, 2007)

Tobacco dependence treatment does not cause abstinent alcoholics to relapse (Hughes & Callas, 2003)

Smoking cessation reduces the risk of alcohol relapse (Sobell et al., 1995)

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Smoking and Alcohol Dependence (Continued)

Bupropion added to nicotine patch did not improve smoking outcomes

Topiramate group was significantly more likely to become abstinent (OR = 4.46) compared with placebo group (Johnson et al., 2003)

Topiramate group reported more weight loss compared with placebo group (44% vs. 18%)

67

Percentage of Patinets With or Without Specific Metal Illness Who Had Quit Smoking at the end of Tobacco Dependence

Treatment

20.5

39.335.9

3437 37

39.6 36

0

5

10

15

20

25

30

35

40

45

Schizophrenia BipoloarDisorder

MDD PTSD

Psychiatric Disorders

Per

cen

t Wh

o Q

uit

Sm

oki

ng

With Diagnosis

Without Diagnosis

Adapted from Grand et al., J Clin Psychiatry, 200768

Benefits of Treating Tobacco Dependence in Mental Healthcare Settings

Emerging evidence shows that morbidity is reduced

May enhance abstinence from other substances

Reduced financial burden Increased self-confidence

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Future Medication Options

FDA. Rimonabant is a cannabinoid receptor inhibitor that blocks the reinforcing effects of nicotine and also

suppresses appetite. Now in phase 3 trials, it has already receive much attention for its potential to

attack 2 major public health epidemics; smoking and obesity.

Electronic cigarette

E-cigarettes were found to have immediate adverse physiologic effects after short time

use that are similar to some of the effects seen with tobacco smoking ; however, the long term health effects of e-cigarette use

are unknown but potentially adverse effects are worthy of further investigation.

CHEST 2012 ; 141 (6) 1400-1406.

MPOWERMPOWER

• M onitor tobacco use.• P rotect people from tobacco use.• O ffer help to quit tobacco use.• W arn about the damages of tobacco

.• E nforce bans on tobacco

advertising, promotion and sponsorship.

• R aise taxes on tobacco products,

Conclusions

Pharmacotherapy works and is relatively safe

Many options now availablePatients should be given accurate

expectations (no magic bullet)

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