2. Smoking Cessation
Gamal Rabie Agmy ,MD ,FCCP
Professor of Chest Diseases, Assiut University

3. Facts about Smoking
 Most 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.

4. 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.

5. Benefits of Smoking Cessation
These 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.

6. 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.

7. 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.

8. Evidence for Effectiveness of Health
Professional Intervention
 A 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.

9. 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.

10. 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 Programs
Helping Smokers Quit (Cessation)
School-Based Programs
Enforcement
Monitoring and Evaluation
Related Policy Efforts

11. Guidelines for
Individual Smoking
Cessation

12. Tobacco dependence is a chronic condition that
often requires repeated intervention. However,
effective treatments exist that can produce longterm abstinence.
These guidelines are designed for smoking
cessation providers to assist all clients with
smoking cessation.

13. Promoting Smoking Cessation
THE FIVE A’S:
ASK
ASSESS
ADVISE
ASSIST
ARRANGE

14. ASK

16. ASSESS

18. Ask

19. ADVISE

23. ASSIST

27. Ranking of nicotine in relation to
other drugs in terms of addiction
Dependence
among users
nicotine>heroin>cocaine>alcohol>caffeine
Difficulty achieving (alcohol=cocaine=heroin=nicotine)>caffeine
abstinence
Tolerance
(alcohol=heroin=nicotine)>cocaine>caffeine
Physical
alcohol>heroin>nicotine>cocaine>caffeine
withdrawal severity
Deaths
nicotine>alcohol>(cocaine=heroin)>caffeine
Importance in
user's daily life
(alcohol=cocaine=heroin=nicotine)>caffeine
Prevalence
caffeine>nicotine>alcohol>(cocaine=heroin)
27

28. 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

29. First-Line Medications
 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)
29

30. 30

31. Reasons for Using NRT
It
31
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.

32. Nicotine withdrawal
 Withdrawal
syndrome
is a collection of signs
and symptoms
caused by abstinence
 Nicotine
 Nicotine
32
or cigarette
withdrawal?
replacement
reduces severity of
withdrawal symptoms

33. Sign of Nicotine Toxicity
•
33
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

34. 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, try
24 to dec. morning craving
Watch for nightmares
Given with or without taper

34
Pros:
-Easy, good
compliance
-Continuous
nicotine
delivery
-OTC
Cons:
-Slow onset
of action
-Skin
reaction,
Insomnia

35. Nicotine Gum
Dosing:
2mg < 25 cigarettes/day
4mg > 25 cigarettes/day
 Length of Treatment:
8-10 weeks (PDR)
Use: Chew and park (oral absorption)
Slow, buccal absorption
Acidic foods ↓ absorption
Pros: Flexible dosing (every 1-2 hours, up to 24
pieces/day)
Keeps mouth busy
OTC
Cons: Need to use correctly (chew and park)
Nausea, Heartburn
Mouth and throat burning
35


36. 36

37. Nicotine Lozenge
 Dosing:
Based on Time To First

Length
of
Treatment:
12 weeks
(PDR)
Cigarette (TTFC)
4 mg ≤ if 30 mins TTFC
2mg > if 30 mins TTFC
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
37

38. Nicotine Nasal Spray
 Dosing:
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

39. 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

40. Nicotine Medications
 Use
40
high enough dose
 Scheduled better than PRN
 Use long enough time period
 Can be combined with Bupropion
 Don’t combine with Varenicline
 Can be combined with eachother
 Have very few contraindications
 Have no drug-drug interactions

41. Efficacy of NRT medications
2.5
1.73
1.66
1.76
2.08
2.27
2
1.5
1
0.5
0
Odds Ratio of 6 month abstinence
Overall
41
Gum
Patch
Inhaler
Nasal spray

42. Withdrawal Symptoms and NRT
***
N.S.
**
***
***
N.S.
*
N.S.
Placebo
Gum
Patch
Combo
50
P < 0.05
** P < 0.01
100
Smoking
Total Withdrawal
150
***
*
200
***
*** P < 0.001
0
42
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).
Adapted from: Fagerström et. al. Psychopharmacology, 1993,
111:3, 271-7

43. 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
43 GUM

44. 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
44
1.98 (1.30-3.00)
1.27 (1.03-1.57)
1.64 (1.22-2.21)
1.87 (1.17-2.99)

45. Smoking with NRT
Relatively
safe
Harm Reduction
Less reinforcing effects
Not a distraction from quit
attempts
(Benowitz 1997, Hartman 1991, Slade 1995)
45

46. Smoking and NRT: IS THAT SAFE?


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.
Slide copied from OASAS.
46
Respiration 69:452-6, 2002 )

47. Conclusions

47
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.

48. Non-Nicotine Pharmacotherapy
 First-line
non-nicotine medications
-Bupropion (Zyban/Wellbutrin)**
-Varenicline (Chantix)**
 Others (nortriptyline, clonidine )
**FDA Approved for smoking cessation
48

49. 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)
49

50. 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%)

–
–
50
–
2nd dose early evening helps
Dry mouth
Headaches
Rash

51. Bupropion Efficacy
50
40
*
*
Placebo
30
*
*
100 mg
150 mg
20
300 mg
10
0
7 week abstinence
51
1 year abstinence
Hurt, 1997

52. Varenicline (Chantix)
 Action
at α4β2 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. Varenicline (Chantix)
 Action
at α4β2 nicotine receptor
 Partial
agonist/antagonist
 Releases lower amounts of dopamine
into brain than smoke
–
–
Reduces withdrawal
Not as addictive as smoke
 Blocks
–
53
nicotine from binding to receptor
Prevents reward of smoking

54. Dosing
 Titrate
CHX 0.5
Pfizer
54
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

55. Abstinence by medication use
100%
74%
80%
64%
60%
40%
20%
82%
52%
37%
31%
37%
42%
42%
20%
0%
No m eds
1 m ed
2 m eds
4-week abstinence
55
3 m eds
4+ m eds
6-month abstinence

56. Serious Mental Illness
 Reduced
Cessation
-Schizophrenia/Schizoaffective disorder
-Bipolar disorder
-PTSD
-Alcohol use disorder
56

57. Smoking and
Schizophrenia
 High
prevalence of smoking (about
90%, OR = 5.9)
 Highly nicotine dependent (FTND = 7
or higher)
 Nicotine produces cognitive or other
benefit
 Smoking ameliorates medication side
effects (e.g., lower rates of
neuroleptic-induced Parkinsonism)
57

58. 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

59. 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

60. Smoking & Bipolar Disorder
 High
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 durable
 Quit rates enhanced with CBT
60

61. 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)
61

62. Link Between MDD and
Smoking
60
50
Lifetime
Prevalence of
Major
Depression (%)
40
30
20
10
0
None
1 to 5
6 to 10
11 to 20
>21
Average Daily Cigarette Consumption
62
Adapted from Kendler KS, 1993

63. Smoking and Depression (Continued)
 NRT
63
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

64. 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:
–
–
–
64
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

65. SSRIs and Smokers with
Anxiety Disorder
 No
benefit for smoking cessation
 Can 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
65

66. Smoking and Alcohol
Dependence
 High
prevalence of smoking: 80-95%
 Two studies reporting similar outcomes
of NRT in alcoholics compared with nonalcoholics (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)
66

67. 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

68. Percentage of Patinets With or Without Specific Metal Illness
Who Had Quit Smoking at the end of Tobacco Dependence
Treatment
45
39.6
Percent Who Quit Smoking
40
39.3
36
35.9
37
35
34
37
30
25
With Diagnosis
20.5
Without Diagnosis
20
15
10
5
0
Schizophrenia
Bipoloar
Disorder
MDD
PTSD
Psychiatric Disorders
68
Adapted from Grand et al., J Clin Psychiatry, 2007

69. 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
69

70. 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.

71. Electronic cigarette

73. 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.

74. MPOWER
•
•
•
•
•
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,

75. Conclusions
Pharmacotherapy
works and is
relatively safe
Many options now available
Patients should be given accurate
expectations (no magic bullet)
75