Conflict Disclosure Info
• Speaker: Winston Tsui
• “Understanding Smoking Cessation Treatment Options
and Their Accessibil...
Disclosure
• I have full editorial control over the content
of this presentation and wish to advise and
that it may contai...
Objectives
• Review the latest clinical literature in smoking cessation and establish
the burden of smoking and its diseas...
Burden of Disease
Tobacco use is the
leading preventable
cause of death in
the world.

World Health Organization: The World Health Report 20...
Tobacco will kill Over 175 million People Worldwide
Between 2005 and 2030

http://www.cancer.org/downloads/AA/TobaccoAtlas...
Tobacco-Related Deaths
are Increasing1,2
Deaths Attributable to Tobacco

Tobacco may kill
one billion people
in the 21st c...
Smoking Prevalence in Canada: 17%
~ 5 Million Smokers

Newfoundland
& Labrador
20%
B.C.
15%

Alberta
18%

Manitoba
18%

Sa...
The Impact of Smoking on Canadians
Almost 5 Million Canadians Smoke1
♦ Smoking is the #1 preventable cause of death in Can...
Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
Smoking Saturates Nicotinic Receptors
MRI: Magnetic resonance image

kBq/mL
9

0
0.0 Cigarette

0.1 Cigarette

Brody AL. A...
What’s in a Cigarette?
♦ Tobacco smoke: ≥ 4000 chemicals1, ≥ 50 carcinogenic2
Chemicals in
Tobacco Smoke1

Also Found In…
...
Why Quit? Potential Lifetime Health
Benefits of Quitting Smoking1-2
Cardiovascular heart disease (CHD) risk is similar to ...
Tobacco Dependence Mechanisms
Mechanism of Action of Nicotine
in the Central Nervous System
♦ Nicotine binds
β2 β2
preferentially to nicotinic
α4 β2 α4
...
FOREBRAIN
Dopamine
BRAIN STEM
α4ß2 receptors

Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
“Smokers smoke to maintain relative
constancy of nicotine, dopamine
and other neurotransmitter levels.”
Slide courtesy of ...
The Cycle of Nicotine Addiction
♦ Nicotine binding causes an increase in
dopamine release 1
♦ Dopamine gives feelings of p...
Quitting Smoking:

May be a Protracted Journey
♦ The majority of smokers are motivated to quit

1

♦ Most try to quit with...
Tobacco Dependence and
Environmental Reinforcement

♦ Pharmacologic effects
– Nicotine as an addictive drug

♦ Non-pharmac...
Withdrawal Syndrome: a Combination of
Physical and Psychological Conditions,
Making Smoking Hard to Treat1,2
Withdrawal Sy...
Withdrawal Symptoms from Stopping Smoking
Incidence
Increased appetite

70%

Restlessness

60%

Depression

60%

Irritabil...
Select Withdrawal Symptoms Over Time
Placebo
Impatience

1.5

Nicotine Gum
Irritability/Anger
1.5
1.0

0.5
de s u d A nae ...
Probability of Dependence After Trying a
Substance at Least Once
Tobacco
Heroin
Cocaine
Alcohol
Stimulants
Anxiolytics
Can...
Pharmacological Smoking Cessation
Treatment Approaches
Pharmacotherapy
for Tobacco Dependence 1-4

3 First-Line Therapies:
♦ Nicotine replacement therapy (NRT)
– Long-acting -- ...
Effectiveness and abstinence rates for various medications and
medication combinations compared to placebo at 6-months pos...
Effectiveness of smoking
cessation interventions
Comparison

# studies

# participants

Pooled Odds Ratio
(95% CI)

Non-ph...
Nicotine Replacement Therapy (NRT)

♦ NRT has been shown to be safe and effective in
helping people stop using cigarettes ...
Nicotine Replacement Therapy (NRT): Nicotine
Delivery by Cigarettes and NRT Products
Cigarette (nicotine delivery, 1-2 mg)...
Efficacy of Nicotine Replacement
Therapy (NRT)
Trials
(n)

Participants
(n)

Pooled RR
(95% CI)

Gum

53

19,090

1.43 (1....
Bupropion SR (Zyban®)
♦ ZYBAN® (bupropion SR hydrochloride) is a non-nicotine
sustained-release tablet for smoking cessati...
Comparison of Nicotine Replacement
Therapy (NRT) and Bupropion SR Therapy
for Quitting Smoking1
♦ Only cessation study com...
Bupropion SR for Tobacco
Dependence
Trials
(n)

Participants
(n)

Pooled OR†
(95% CI)

Bupropion SR alone vs.
Placebo

19
...
Varenicline: An α4β2 Nicotinic Acetylcholine
Receptor Partial Agonist and Antagonist
♦ ACTIVITY 1: Partial agonist
– Varen...
Varenicline Comparative Studies Design1,2
Treatment phase

Non-treatment phase

Varenicline 1 mg BID†
Bupropion 150 mg BID...
Varenicline Comparative Studies
Primary/Secondary End Points
♦ Primary End Point1-3
– 4-Week Continuous Quit Rate (CQR), d...
Varenicline Comparative Studies 4-Week
Continuous Quit Rates Weeks 9–121,2
50
45
40
35
30
25
20
15
10
5
0

44.0%
†

Study ...
Varenicline Comparative Studies
Continuous Abstinence (CA) Rates Weeks 9–521,2
Study 1/Gonzales et al.1

Study 2/Jorenby e...
Varenicline Maintenance of Abstinence
(Extended Therapy) Study Design
Non-treatment
Double-blind phase follow-up phase

Op...
Varenicline Maintenance of Abstinence
Study Primary/Secondary End Points
♦ Primary End Point1,2
– Carbon monoxide (CO)-con...
Maintenance of Abstinence (Extended Therapy)
in Quitters that had Previously Received
12 Weeks of Varenicline Therapy
1210...
Varenicline Maintenance of
Abstinence Study: Adverse Events
Most Frequent AEs (Open-label Varenicline)
Open label
Varenicl...
Comparison of Pharmacological
Interventions for Smoking Cessation
Comparison

# studies

# participants

Pooled
OddsRatio ...
Long-Term Safety Study Conclusions
♦ Varenicline at a dose of 1 mg bid, can safely be taken for
periods up to one year
♦ A...
Varenicline Summary
♦ An innovative smoking cessation therapy believed to have simultaneous partial
agonist and antagonist...
CHAMPIX (Varenicline)
Indication and Dosing Information
♦ Indicated for smoking cessation treatment in adults in conjuncti...
Varenicline Safety Information
♦ Established safety and tolerability profile assessed in approximately
2,300 subjects
♦ In...
CHAMPIX (Varenicline)
Key Points to Keep in Mind:
♦ Identify patients who are motivated to quit smoking, since
motivated q...
Cost of Champix
♦ Starter pack (week 1 & 2): $42
♦ Continuation: $47
♦ One month: $94
♦ Cigarettes (1 ppd) for 1 month: $2...
Cardiovascular Concerns
♦ In 2011, the FDA issued an advisory that varenicline may
increase the risk of adverse cardiovasc...
Cardiovascular Concerns
♦ Risk of serious adverse cardiovascular events associated with
varenicline: a systematic review a...
Cardiovascular Concern
♦ Risk of cardiovascular serious adverse events
associated with varenicline use for tobacco
cessati...
♦ Over the long term, even in a higher risk population
of patients with stable CVD, the benefits of smoking
cessation like...
People who quit
smoking after a
heart attack or
cardiac surgery
reduce their risk
of death by 36%

Cochrane Database of Sy...
Model of Deaths Prevented or Postponed
Through Risk-Factor Reduction
Coronary Heart Disease Deaths in England

Unal B et a...
Neuropsychiatric effects
♦ In 2008 FDA from post marketing reports suggested
patients should be monitored for neuropsychia...
Neuropyschiatric Affects
♦ In contrast, a pooled analysis of 10 randomized
placebo-controlled trials in 5096 smokers found...
BC Smoking Cessation Program

Effective September 30th, 2011, Pharmacare
launched the B.C. government’s Smoking
Cessation ...
Patient eligibility criteria
♦ To be eligible for nicotine replacement therapy program, patients must
have valid, active M...
Coverage Details
♦ Each calendar year, eligible B.C. residents may receive one or the
other of the following:
– Coverage f...
Coverage details continued..
Handling requests for prescription drugs – key points
♦ You do NOT need to obtain Special Aut...
For More Information…

♦ Visit the Ministry of health website at www.health.gov.ca/pharmacare/stopsmoking/ for more inform...
Non-Pharmacological Smoking Cessation
Treatment Approaches
A Comprehensive Approach
to Smoking Cessation
♦ Nicotine addiction has two main components:
– the pharmacological action o...
Why May Some Smokers Need More
Help to Quit ?
♦ Higher level of dependence 1
– Cigarettes per day
– Time to first cigarett...
Non-pharmacologic Approaches
Advice and Support 1-3
♦ All smokers should be:
– Advised to quit
– Offered assistance
♦ Non-...
Office-based Strategies for Helping
Patients Quit Smoking
♦ A systematic approach to identifying smokers1
♦ Sharing respon...
Brief Tobacco Intervention
Using the 5 A’s
♦ Identify and document tobacco use

ASK

♦ In a clear, strong, personalized ma...
Baseline assessment of the smoking status:
The Fagerström Test for Nicotine Dependence 1,2
Questions

Answers

1. How soon...
The “5As”: Advise to Quit
♦ In a clear, strong, and personalized manner, urge every tobacco
user to quit at least once per...
The “5As”: Assist in Quit Attempt
♦ For the patient willing to make a quit attempt, use counselling and
pharmacotherapy
– ...
The “5As”: Arrange Follow-up
♦ Schedule follow-up contact, preferably within the first week after
the quit date
♦ Follow-u...
Smoking Cessation Effectiveness
Increases with Treatment Intensity
Meta-analysis (2000): Effectiveness of and estimated ab...
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
Smoking cessation presentation   dr. tsui - abbotsford, june 6, 2012
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  • Reference
    WHO: The World Health Report - Shaping the Future. Geneva, Switzerland; 2003. 204 p.;http://www.who.int/whr/2003/en/
  • Reference:
    Shafey O, et al. Chapter 10: Deaths. The Tobacco Atlas, 3rd Edition. American Cancer Society 2009; Atlanta, GA.
  • Key Point:
    Worldwide, millions of people each year die from smoking and tobacco related diseases. Recent figures show that deaths are equally distributed between developed and developing countries.
    Background:
    In 2000, 4.8 million people worldwide died from tobacco-related illnesses.1 Previously, mortality from tobacco was higher in developed compared with developing countries. However, in 2000, the mortality rates were identical at 2.4 million.2 This represents an exponential increase in tobacco-related mortality in the developing world, rising from negligible levels in 1950, to 0.2 million2 in 1975, and to 4.8 million in 2000.1 And according to the World Health Organization, this figure rose to 4.9 million, in 2002.3
    References:
    Mackay J, Eriksen M, Shafey O. The Tobacco Atlas. 2nd ed. Atlanta, Georgia: American Cancer Society; 2006. Available at: http://www.myriadeditions.com/statmap/. Accessed February 27, 2007.
    Mackay J, Eriksen M. The Tobacco Atlas. 1st ed. Geneva, Switzerland: World Health Organization; 2002. Available at: http://www.who.int/tobacco/en/atlas11.pdf. Accessed February 27, 2007.
    World Health Organization. International treaty for tobacco control, 2003. Available at: http://www.who.int/features/2003/08/en. Accessed February 27, 2007.
  • Key Point(s):
    According to the Wave 1, 2007 results of the CUTMS, (data collected between February and June 2007), almost 5 million people were current smokers. This represents 19% of the population aged 15 years and older.
    The prevalence of smokers in Canada varies across the provinces, from a low of 15% in British Columbia to a high of 25% in Saskatchewan.
    Background:
    The Canadian Tobacco Use Monitoring Survey (CTUMS) was developed to collect data on tobacco use and related issues. Data are based on interviews conducted by Statistics Canada. “The survey's primary objective is to track changes in smoking status and amount smoked, especially for 15-24-year-olds, who are most at risk for taking up smoking.”
    Reference:
    Health Canada. Canadian Tobacco Use and Monitoring Survey (CTUMS), Results from Wave 1, 2007. January 21, 2008. Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/research-recherche/stat/ctums-esutc_2007-eng.php. Accessed August 20, 2008.
  • Key point:
    22% of deaths in Canada can be attributed to smoking, representing the number one risk factor for preventable disease and death. Smoking affects both smokers and non-smokers.2
    References:
    Health Canada. Canadian Tobacco Use Monitoring Survey 2005, Summary of Annual Results. Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/research-recherche/stat/ctums-esutc/2005/index_e.html. Accessed February 27, 2007.
    Makomaski Illing EM, Kaiserman, MJ. Mortality attributable to tobacco use in Canada and its regions, 1998. Can J Public Health 2004;95:38-44.
  • Key Point:
    The typical number of cigarettes smoked per day results in nearly complete occupancy of the 4β2 nicotinic acetylcholine (nACh) receptors in the brain; for tobacco-dependent smokers, this means that 4β2 nACh receptor saturation is maintained throughout the day.
    Background:
    To determine the effect of cigarette smoking on 4β2 nACh receptor occupancy, typical tobacco-dependent smokers smoked 0, 1 puff, 3 puffs, 1 cigarette, or 3 cigarettes. 50% 4β2 nACh receptor occupancy occurred after smoking 13% of a cigarette (i.e., 1 to 2 puffs). The corresponding plasma nicotine concentration was 0.87 ng/ml, which represents ~1/25 of the daily plasma nicotine levels of typical smokers. Furthermore, 50% 4β2 nACh receptor occupancy lasted for 3 hrs. Smoking 1 cigarette lead to 88% receptor occupancy and reduced cravings.
    Reference:
    Brody AL. Arch Gen Psychiatry 2006;63:907-915.
  • Key Point:
    Tobacco smoke exposes the body to 50 carcinogenic chemicals2.
    Background:
    Tobacco and tobacco smoke are known to be carcinogenic in humans. Tobacco smoke contains at least 4000 chemicals1, at least 50 of which are carcinogenic.2 For example, tobacco smoke contains irritants, such as acetone, ammonia, and toluene, found in paint stripper, cleaners, and solvents respectively. In addition, there are toxic heavy metals, such as cadmium, used in car batteries, and arsenic, used in poisons. And finally, carbon monoxide, which is a hazardous component of exhaust fumes, is present in cigarette smoke.1 Nicotine is responsible for the addiction, but other chemicals are also involved. All cigarettes are toxic: the World Health Organization reports that smoking cigarettes with lower yields of tar and nicotine provides no health benefit.1
    References:
    WHO. Tobacco: deadly in any form or disguise. WHO Library Cataloguing-in-Publication Data, 2006. Available at: http://www.who.int/tobacco/resources/publications/wntd/2006/en/index.html. Accessed February 11, 2007.
    Health Canada. What’s in cigarette smoke? August 2005. Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/body-corps/habit/smoke-fumee/index_e.html. Accessed February 11, 2007.
    O’Donnell DE et al. State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
  • Key Point:
    The health benefits of quitting smoking start immediately and are sustained such that 15 years after quitting smoking, the coronary heart disease risk of a former smoker is equal to that of a nonsmoker.
    Background:
    When gauging the health benefits from smoking cessation one is encouraged to assess both the short-term and long-term improvements. Within 2 weeks to 3 months lung function may begin to improve and there may be notable decreases in coughing, sinus congestion, fatigue and shortness of breath.
    Around the year mark, coronary heart disease risk, the leading cause of death in the United States, improves with smoking cessation to a point where excess risk is reduced by 50% and continues to decline thereafter. Within the 5-15 year range, the risk of stroke for smoking cessators returns to the level of a person who has never smoked.
    Other potential long-term benefits include: the risk of lung cancer, the most common cause of cancer death in the United States, declines steadily after smoking cessation; and by 10 years after cessation, the risk of lung cancer is 30-50% that of continuing smokers. And beyond this, smoking cessation may also reduce the risk of cancers of the larynx, oral cavity, esophagus, pancreas, urinary bladder and of developing ulcers of the stomach or duodenum. Other long-term benefits include the reduced risk of coronary heart disease (CHD). After 15 years of abstinence, risk of CHD becomes similar to that of a person who has never smoked. A patient has clear health benefits to gain if they successfully stop smoking.
    References:
    CDC. Surgeon General’s 2004 Report. The Health Consequences of Smoking on the Human Body. Online slides. Available at: http://www.cdc.gov/tobacco/sgr/sgr_2004/sgranimation/flash/index.html. Accessed April 15, 2006.
    American Cancer Society. Guide to Quitting Smoking. Available at: http://www.cancer.org. Accessed June 2006.
    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.
  • Key Point:
    Nicotine stimulates dopamine release in areas of the brain which is believed to result in the reward and satisfaction effect associated with smoking.1
    Background:
    After inhalation, nicotine preferentially binds to 4β2 nicotinic acetylcholine receptors located in the mesolimbic-dopamine system of the brain within a matter of seconds.1-3 Nicotine specifically activates 4β2 nicotinic acetylcholine receptors (pentameric structures composed of 5 subunits, i.e., two 4 and three 2 subunits) in the Ventral Tegmental Area (VTA) causing an immediate dopamine release at the Nucleus Accumbens (nAcc). The dopamine release is believed to be a key component of the reward circuitry associated with cigarette smoking.1
    References:
    Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract 2006;60:571-576.
    Jarvis MJ. ABC of smoking cessation: Why people smoke. BMJ 2004;328:277-279.
    Health Canada. Smoking and your body: Addiction. Available at: http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/body-corps/nicotine/addiction-dependance/index_e.html. Accessed January 5, 2007.
  • Key Point:
    Nicotine addiction is a cycle which begins with nicotine binding to receptors in the brain causing the release of dopamine which in turn results in feelings of pleasure and calmness.1,2
    Background:
    The distribution of nicotine is very rapid. It can reach the brain within 10 to 16 seconds after inhaling cigarette smoke.3
    The binding of nicotine to its relevant receptors results in the release of multiple neurotransmitters, most critically dopamine. The release of dopamine in the nucleus accumbens neurons is thought to play a critical role in the addictive nature of nicotine. This release of dopamine requires binding of nicotine to 42 nicotinic acetylcholine receptors.1,2
    Absorption of cigarette smoke from the lungs is rapid and complete, producing with each inhalation a high concentration of arterial nicotine that reaches the brain within 10 to 16 seconds. Nicotine has a terminal half-life in blood of 2 hours. Smokers therefore experience a pattern of repetitive and transient high blood nicotine concentrations from each cigarette.3 Nicotine’s activation of nicotinic acetylcholine receptors induces the release of dopamine in the nucleus accumbens. This is similar to the effect produced by other drugs of misuse, such as amphetamines and cocaine.1 The symptoms of nicotine withdrawal are a major barrier to smoking cessation. Smokers start to experience impairment of mood and performance within hours of their last cigarette. These effects are completely alleviated by smoking a cigarette. Withdrawal symptoms include irritability, restlessness, feeling miserable, impaired concentration, and increased appetite, as well as craving for cigarettes. Cravings, sometimes intense, can persist for many months.3
    References:
    Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract 2006;60:571-576.
    Fagerstrom K. The epidemiology of smoking: Health consequences and benefits of cessation. Drugs 2002;62(Suppl2):1-9.
    Jarvis MJ. Why people smoke. BMJ 2004;328:277-279.
  • Key point:
    Quitting smoking is a long and difficult journey. The Prochaska model allows health care professionals to identify where a patient sits on a “stage of change” continuum which includes contemplation, preparation, action, maintenance and relapse.1,2
    Background:
    A very high proportion of smokers have tried to quit4†, and in general they make 5-7 attempts before succeeding3. Many of these smokers who relapse quote cravings as the most common reason why quitting is considered difficult.4‡
    †Based on an online national survey conducted by Leger Marketing between August 30 and September 20, 2006. 1440 randomly selected respondents aged between 18 and 65 answered “Yes” or “No” to the question: “Have you ever attempted to quit smoking?”4
    ‡Based on an online national survey conducted by Leger Marketing August 30 and September 20, 2006. 1319 randomly selected respondents answered the question: “Approximately how many times have you tried/did you try to quit smoking in total?”4
    References:
    Prochaska JO et al. In search of how people change: Applications to addictive behaviours. Am Psychol 1992;47:1102-1114.
    O’Donnell DE et al.State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
    Hughes JR. New treatments for smoking cessation. CA Cancer J Clin 2000;50:143-151.
    Pfizer Canada Inc., Data on file. 2006.
  • Key Point:
    The direct pharmacologic effects of nicotine are necessary to, but do not entirely explain, tobacco dependence. Environmental/social stimuli, such as a particular time of day or a particular place (eg, smoking after a meal or in a favourite chair), are important in maintaining smoking behaviours.
    Background:
    Both animal and human experiments suggest that the direct pharmacologic effects of nicotine are necessary, but not sufficient, to explain tobacco dependence; non-pharmacologic factors also play a critical role in smoking behaviours. Nicotine rapidly delivered to the brain is a primary reinforcer of smoking (pharmacologic effects). However, environmental/social stimuli associated with smoking (non-pharmacologic effects) are also important. The pharmacologic and non-pharmacologic aspects of this process may be synergistic: the reinforcing effects of environmental/social stimuli are believed to be strengthened by nicotine.
    Reference:
    Caggiula AR et al. Importance of non-pharmacological factors in nicotine self-administration. Physiol Behav 2002;77:683–687.
  • Key Point:
    Nicotine withdrawal syndrome is characterized by a combination of physical and psychological conditions, which make smoking difficult to treat.
    Background:
    Recognizing that nicotine withdrawal results in clinically significant impairment in a person’s ability to function, the American Psychiatric Association’s Diagnostic and Statistical Manual(DSM) classifies these symptoms as a distinct condition: nicotine withdrawal syndrome. The symptoms of nicotine withdrawal syndrome can develop rapidly after a smoker tries to quit, and characteristics include the psychological symptoms of dysphoric or depressed mood; anxiety; irritability, frustration, or anger; and restlessness or impatience and the physical symptoms of insomnia, increased appetite/weight gain, and difficulty concentrating. Although present in those who use other nicotine-containing products, the manifestations of nicotine withdrawal syndrome are more intense in individuals who smoke compared with those who use other forms of tobacco. The rapidity of onset and intensity of withdrawal syndrome in smokers may suggest a greater dependence on tobacco.1
    The typical duration of most of these symptoms is <4 weeks. Increased appetite is an exception, often lasting for >10 weeks. Although anxiety is listed as a classic symptom of nicotine withdrawal in the DSM, additional information is available about the relationship between anxiety and smoking. Some evidence suggests that while smokers increase their smoking when stressed, smoking does not help relieve the stress. As smokers stop smoking, levels of stress and anxiety actually decrease.2
    References:
    Diagnostic and Statistical Manual of Mental Disorders, IV-TR. Washington, DC: APA; 2006: Available at http://psychiatryonline.com. Accessed November 7, 2006.
    West RW et al. Fast Facts: Smoking Cessation. 1st ed. Oxford, United Kingdom. Health Press Limited, 2004.
  • Key Point(s):
    The duration and incidence of nicotine withdrawal symptoms vary with each symptom.
    Background:
    Withdrawal symptoms represent a major cause of quitting failure. They include: increased appetite, restlessness, depression, irritability or aggression, craving for nicotine, poor concentration, sleep disturbances and lightheadedness. These symptoms start occurring within hours of smoking the last cigarette, and their intensity is at its highest during the first week following smoking cessation. The majority of affective withdrawal symptoms last 3 to 4 weeks, whereas increased appetite and craving for nicotine can last several months.
    Reference:
    Jarvis MJ. ABC of smoking cessation. Why people smoke. BMJ 2004;328:277-9.
  • Key Point
    Common nicotine withdrawal symptoms including impatience, irritability, and anxiety typically resolve in 5 to 6 weeks following abstinence; these withdrawal symptoms can be decreased with nicotine replacement therapy (NRT) therapy. Other withdrawal symptoms, such as excessive hunger, may last well beyond this initial 5 to 6 week period.
    Background
    To investigate the long-term effects of NRT on tobacco withdrawal symptoms, this community-based, double-blind, randomized study monitored 40 volunteers chewing 2 mg of NRT gum or placebo gum over the first 10 weeks after stopping smoking.
    Smoking abstinence over the course of the study was verified using carbon monoxide testing.
    For the first week after quitting, individuals in the NRT gum group experienced significant decreases in irritability, anxiety, impatience, restlessness, excessive hunger, difficulty concentrating, drowsiness, sleep disturbance, and tobacco craving intensity vs individuals in the placebo gum group (P<.01).
    For increased appetite and excessive eating, the NRT gum group scored consistently lower throughout the study period. However, irritability, anxiety, and impatience symptoms declined over time in the placebo group so that, by week 5 or 6 through study end, there was no difference between groups for these symptoms.
  • Key Point:
    Pharmacotherapies approved in Canada for quitting smoking include NRT (i.e., nicotine gum, inhaler and patch), the antidepressant bupropion SR, and the nicotinic acetylcholine receptor partial agonist varenicline.1-4
    Background:
    NRTs assist smokers in quitting by replacing nicotine that would otherwise be smoked, thereby reducing the need to smoke to obtain nicotine.2 Nicotine replacement therapy is available in many forms. Nicotine gum delivers nicotine through the oral mucosa. Nicotine patches, which deliver nicotine through the skin, provide a passive, longer acting system of delivery.1
    Antidepressant therapies, specifically bupropion SR, are also used to help smokers quit. Another antidepressant, nortriptyline has not been as widely studied and has not been approved for smoking cessation in Canada or in the US. Both NRT and bupropion SR have been shown to double quit rates.1,2
    A novel smoking cessation pharmacotherapy, the nicotinic acetylcholine receptor partial agonist varenicline, has recently been approved for use in Canada. Two studies have revealed that quit rates achieved with this therapy were approximately double that of bupropion SR and approximately quadruple that of placebo.2,4-7
    References:
    O'Donnell DE et al.State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
    Foulds J. The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline. Int J Clin Pract 2006;60:571-576.
    Challenge Quit to win. Pharmacological aids. February 20, 2007. Available at: http://www.defitabac.qc.ca/defi/fr/cesser_de_fumer/les_methodes_d_aide/les_aides_pharmacologiques.html. Accessed February 26, 2007.
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    Coe JW et al. Varenicline: An α4β2 nicotinic receptor partial agonist for smoking cessation. J Med Chem 2005;48:3474-3477.
    Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
  • Reference:
    Fiore MC et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence: 2008 Update. US Department of Health and Human Services. Public Health Service. May 2008. Available at: http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf
  • Key Point:
    The effectiveness of the various smoking cessation strategies is expressed in terms of the Odds Ratio (OR), a measure that provides a useful statistic to compare the success of an intervention relative to a reference across different trials.
    Background:
    A comparison of absolute rates would be difficult due to the varying placebo rates in the studies. The OR measure allows for comparisons across studies. The use of Odds Ratios for response rates is standard practice in smoking cessation guidelines and summary documents such as the United States clinical practice guidelines8, the guidance of the National Institute for Clinical Excellence in the United Kingdom9, or the Cochrane Systematic Reviews5 An Odds Ratio greater than 1 implies that smoking cessation has a “greater probability” of occurring with a given intervention as compared to another. For example, with group counselling, the Odds Ratio of 2.17 indicates that there is a two times greater probability that smoking cessation will be achieved or a doubling of the success rate as compared to no intervention.
    References:
    1. Lancaster T, Stead LF. Self-help interventions for smoking cessation. Cochrane Database Syst Rev 2005;(3):CD001118.
    2. Lancaster T. Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev 2005;(2):CD001292.
    3. Lancaster T, Stead LF. Physician advice for smoking cessation. Cochrane Database Syst Rev 2004;(4):CD000165.
    4. Stead LF, Lancaster T. Group behaviour therapy programmes for smoking cessation. Cochrane Database Syst Rev 2005;(4):CD001007.
    5. Silagy C et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2004;(3):CD000146.
    6. Stead L, Lancaster T. Nicotine replacement therapy for smoking cessation: Cochrane systematic review. Int J Epidemiol 2005;34:1001–1003.
    7. Hughes JR et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2004;(4):CD000031.
    8. Fiore MC et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service. June 2000.
    9. National Institute of Clinical Excellence Guidance. Guidance on the use of nicotine replacement therapy (NRT) and bupropion for smoking cessation - full guidance. March 2002. Available at: http://www.nice.org.uk/pdf/NiceNRT39GUIDANCE.pdf.
  • Key Point:
    NRT has been shown to be safe and effective in helping people stop using cigarettes when used as part of a comprehensive smoking cessation program.
    Background:
    Nicotine replacement therapies assist smokers in quitting by replacing nicotine that would otherwise be smoked, thereby reducing the need to smoke to obtain nicotine.1 NRT is available in many forms. Nicotine replacement gum, lozenges, sublingual tablets, inhalers and nasal spray deliver nicotine through the oral or nasal mucosa.
    The consistent use of one of these products doubles a person's odds of quitting smoking. However, NRT does not “make” you stop smoking. Behavior change and support are essential. A smoking cessation program can take many forms, including self-help booklets and telephone counselling. In general, the more intense the behavior modification therapy, the greater the chance of success.
    Nicotine is the addictive substance in tobacco products. NRT provides nicotine so the body doesn't have to endure nicotine withdrawal while a person adapts to not smoking. Trying to learn skills to help in quitting smoking while dealing with nicotine withdrawal makes it harder to successfully quit.
    Nicotine withdrawal symptoms include irritability, difficulty concentrating, feelings of depression, difficulty sleeping, increased appetite cravings and headache. These symptoms often start just a few hours after the last cigarette. The first 72 hours of quitting are the hardest, but symptoms may persist for weeks. Smokers have learned that a cigarette will relieve these symptoms in a few moments. But taking nicotine in another form can suppress withdrawal.
    NRT products only provide nicotine. They contain none of the carcinogens or toxic substances found in cigarette smoke.
    References:
    American Heart Association website: http://www.americanheart.org/presenter.jhtml?identifier=4615. Accessed November 5, 2006.
    Sweeney CT et al.Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001;15:453–467.
  • Key Point:
    Most NRT methods typically don’t deliver nicotine as rapidly and at the same level as cigarette smoking.
    Background:
    No individual NRT currently available when administered as indicated matches the intensity and pattern of nicotine delivery of a cigarette, which delivers high levels of nicotine within minutes of smoking that gradually taper down over time. A slow delivery system, such as that of the nicotine patch, provides a more constant concentration of nicotine in the plasma to relieve cravings and tobacco withdrawal symptoms over time, whereas delivery methods that are faster acting, such as nasal spray or gum, can be used on demand for immediate relief of breakthrough cravings.
    Reference:
    Sweeney CT et al.Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001;15:453–467.
  • Key Point:
    All types of NRT increase the odds of quitting, with little difference among methods.
    Background:
    A Cochrane systematic review of the NRT literature found that all types of NRT significantly increase the odds of quitting with little difference between methods. However, NRT efficacy compared with placebo remains suboptimal with an OR of 1.77, ranging from 1.66 for gum to 2.14 for the inhaler.1,2
    Reference:
    Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000146.
  • Key Point:
    Zyban® is a non-nicotine aid to smoking cessation.
    Background:
    The recommended and maximum dose of Zyban® is 300 mg/day, given as 150 mg twice daily. Dosing should begin at 150 mg/day given every day for the first 3 days, followed by a dose increase for most patients to the recommended usual dose of 300 mg/day. It is important that patients continue to receive counselling and support throughout treatment with Zyban®, and for a period of time thereafter.
    PrZyban® is a registered trademark of the GlaxoSmithKline Group of Companies and is used by Biovail under license.
    Reference:
    Product Monograph. bupropion SR hydrocloride [Zyban®]. GlaxoSmithKline.
  • Key Point:
    In the only head-to-head comparison of NRT and bupropion SR therapy for quitting smoking, bupropion SR was more effective at 12 months. Further research is needed.
    Background:
    Only one head-to-head study has compared treatment with bupropion SR, the NRT patch, bupropion SR plus patch, and placebo.1,2 This double-blind, placebo-controlled trial randomized 244 patients to receive bupropion SR monotherapy, 244 to receive NRT patch monotherapy, 245 to receive both therapies, and 160 patients to placebo. Bupropion SR therapy was comprised of 150 mg per day for the first 3 days plus matching placebo, then 150 mg twice daily. Patients received 9 weeks of bupropion SR therapy and/or used the patch for 8 weeks. The study excluded smokers with clinical depression.1
    The 1 year continuous abstinence rates were significantly higher in the groups that received bupropion SR (18.4%) or bupropion SR plus the patch (22.5%) compared with the group that used the patch alone (9.8%) and the placebo group (5.6%) (p<0.001). The trend was similar for 1 year 7-day point prevalence of abstinence, with 15.6% of the placebo group, 16.4% of the patch-alone group, 30.3% of the bupropion SR-alone group (p<0.001), and 35.5% of the group that received bupropion SR plus the patch still remaining abstinent from smoking (p0.001 for the bupropion SR groups vs. patch alone and placebo). Although abstinence rates were higher with combination therapy, the difference was not significantly different from the rate for the bupropion SR monotherapy group.
    References:
    Jorenby DE et al.A controlled trial of sustained-release bupropion SR, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685–691.
    Talwar A, Jain M, Vijayan VK. Pharmacotherapy of tobacco dependence. Med Clin North Am 2004;88:1517–1534.
  • Key Point:
    Data from multiple trials have outlined the efficacy of specific antidepressant therapy (bupropion SR, nortriptyline) for quitting smoking.
    Background:
    Multiple trials have been conducted investigating antidepressant therapy, including bupropion SR SR, nortriptyline, and several selective serotonin-reuptake inhibitors, for quitting smoking. A Cochrane review of the literature found 24 trials studied the use of bupropion SR therapy either alone or in combination with other methods (e.g., nicotine replacement therapy [NRT]). Analysis of data from 19 trials that investigated Bupropion SR monotherapy resulted in an OR of 2.06 for success in quitting smoking.
    Two trials of bupropion SR plus NRT patch treatment compared with placebo yielded an OR of only 1.60. The combined OR for all trials of bupropion SR versus placebo was 1.99.1
    Compared with bupropion SR, fewer trials have been conducted with nortriptyline (24 vs. 6, respectively), and in the whole of the published literature, it has only been tested for quitting smoking in approximately 500 smokers.1,2 A Cochrane analysis of all available data revealed an OR of 2.14 for quitting smoking. This increased slightly to 2.79 when only the trials of nortriptyline monotherapy were included in the analysis.1
    There is limited or no evidence of long-term benefit with other antidepressants including the monoamine oxidase inhibitor, moclobemide, the atypical, venlafaxine, or the selective serotonin reuptake inhibitors, fluoxetine, sertraline, and paroxetine.1
    References:
    1. Hughes J, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2004;(4):CD000031.
    2. Hughes JR, Stead LF, Lancaster T. Nortriptyline for smoking cessation: a review. Nicotine Tob Res 2005;7:491–499.
  • Key Point:
    The efficacy of varenicline in smoking cessation is believed to be a result of varenicline’s partial agonist activity at the 42 nicotinic acetylcholine receptor (i.e., agonist activity to a lesser degree than nicotine), while simultaneously preventing nicotine binding (i.e., antagonist activity).
    Background:
    Electrophysiology studies in vitro and neurochemical studies in vivo have shown that varenicline acts as a partial agonist at 42 nicotinic acetylcholine receptors. In the absence of nicotine, varenicline’s agonist activity is at a significantly lower level than nicotine, but sufficient to activate the central nervous mesolimbic dopamine system, believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking. In the presence of nicotine, which competes for the same human 42 nicotinic acetylcholine receptor binding site, varenicline prevented nicotine from activating the 42 nicotinic acetylcholine receptor, since it has higher affinity for this site. This prevented full stimulation of the central nervous mesolimbic dopamine system.
    Reference:
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
  • Key Point:
    The two Phase 3 studies included 12 weeks of active treatment with non-pharmacologic follow-up for 40 weeks.1,2
    Background:
    Patients enrolled in the two Phase 3 studies were screened via a telephone interview and 2 clinic visits.2 Target quit date was set for 8 days after the first visit (week 1).1,2 Patients were randomized to receive either varenicline titrated as 0.5 mg once daily for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1.0 mg twice daily; bupropion SR titrated as 150 mg once daily for days 1 to 3, then 150 mg twice daily; or placebo for 12 weeks.1,3 This active-treatment period was followed by a 40-week off-treatment period, for a total study duration of 52 weeks. During the follow-up period, patients visited the clinic on weeks 13, 24, 36, 44, and 52. During these visits, patients received brief (≤10 minutes) smoking cessation counselling following recommendations in the Public Health Service Clinical Practice Guideline, and cigarette/tobacco use, vital signs, expired carbon monoxide, and use of smoking cessation medications were assessed. For weeks 16, 20, 28, 32, 40, and 48, patients were contacted by telephone, and use of tobacco and smoking cessation medications was assessed.1,2
    References:
    Gonzales D et al. Varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
  • Key Point:
    The studies’ primary end point was patient-reported continuous quit rate (CQR) for the last 4 weeks of treatment, confirmed by exhaled carbon monoxide testing.1-3
    Background:
    For both studies, the primary end point was the 4-week continuous quit rate for weeks 9 through 12 of the active-treatment period. This response rate was defined as complete abstinence from smoking (not even a puff) or use of any tobacco-containing products as reported by the participant, confirmed by an exhaled carbon monoxide measurement of ≤10 ppm. Secondary end points included the rate of CA from week 9 through week 24 and from week 9 through week 52 of the study as reported by the participant and confirmed by carbon monoxide testing. Other secondary endpoints also included Smoking Abstinence Point Prevalence verified by carbon monoxide level at 7 days.1-3
    References:
    Gonzales D et al. Varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
  • Key Point:
    In both studies, varenicline resulted in continuous quit rates (CQR) at weeks 9 through 12 that were significantly higher than for placebo or bupropion SR.1,2
    Background:
    For the primary end point of carbon monoxide (CO)–confirmed, 4-week CQR were defined as patient report and exhaled CO ≤10 ppm. 4-week CQR with varenicline treatment were significantly higher compared with bupropion SR treatment or placebo.1,2 In study 1, 44.0% of participants in the varenicline group were continuously abstinent from smoking during weeks 9 through 12 compared with 29.5% of participants in the bupropion SR group and 17.7% of participants in the placebo group (both p<0.001). This translated to an abstinence OR of 3.85 for varenicline vs. placebo and an OR of 1.93 vs. bupropion SR.1 Similarly, in study 2, 4-week CQR for varenicline, bupropion SR, and placebo were 43.9%, 29.8%, and 17.6%, respectively. Varenicline was significantly more effective compared with placebo (OR, 3.85; p<0.001) and bupropion SR (OR, 1.90; p<0.001).2 Subjects were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counselling at each clinic visit in accordance with the US Public Health Service Clinical Practice Guideline.1,2
    References:
    Gonzales D et al. Varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an 42 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
  • Key Point:
    Rates of continuous abstinence (CA) from smoking for weeks 9 through 52 were significantly higher for varenicline compared with placebo.1,2 Compared with bupropion SR, varenicline rates were statistically higher in one study (p=0.004)2 and trended toward significance in the other (p=0.057, NS).1
    Background:
    In study 1, 21.9% of participants in the varenicline group maintained CA from smoking during this time period vs. 16.1% of participants in the bupropion SR group and 8.4% of participants in the placebo group (p=0.057, NS and p<0.001, respectively). The OR for varenicline for this measure was 3.09 vs. placebo (p<0.001) and 1.46 vs. bupropion SR (p=0.057, NS).1 In study 2, the CA rates for weeks 9 through 52 for varenicline, bupropion SR, and placebo were 23.0%, 14.6%, and 10.3%, respectively. Varenicline was significantly more effective compared with placebo (OR, 2.66; p<0.001), and bupropion SR (OR, 1.77; p=0.004).2
    Subjects were provided with an educational booklet on smoking cessation and received up to 10 minutes of smoking cessation counselling at each clinic visit in accordance with the US Public Health Service Clinical Practice Guideline.1,2
    References:
    Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
  • Key Point:
    In the maintenance study, patients received one 12-week open-label course of varenicline treatment; then responders were randomized to receive either placebo or varenicline for a further 12 weeks. Patients were followed for 28 weeks after treatment completion for a total study duration of 52 weeks.
    Background:
    The maintenance study by Tonstad and colleagues was comprised of 3 phases. In the first, open-label, active-treatment phase, all participants received varenicline, which was titrated as 0.5 mg once daily for 3 days, 0.5 mg twice daily for 4 days, then 1.0 mg twice daily for 11 weeks. Participants were instructed to attempt to quit smoking 1 week after taking study medication, but were allowed to quit earlier if they wished to do so. Participants visited the clinic at weeks 1 through 8, 10, and 12.
    Those who had been abstinent from smoking for the 7 days prior to the week 12 visit and had not used nicotine replacement therapy were eligible to enter the randomized, double-blind phase of the study, in which participants were randomized to receive a further 12 weeks of varenicline or to be switched to placebo. During this second phase, participants visited the clinic at study weeks 13, 14, 16, 20, and 24.
    This double-blind phase was followed by a 28-week, non-treatment, participant-blinded, follow-up phase, for a total study duration of 52 weeks. During the follow-up phase, patients visited the clinic at study weeks 25, 28, 36, 44, and 52 and were contacted by telephone at weeks 26, 32, 40, and 48.
    At all points of contact for all study phases (clinic visits and telephone conversations), patients were asked about their use of cigarettes/tobacco and other products containing nicotine. Exhaled carbon monoxide was tested at each clinic visit. Subjects received up to 10 minutes of smoking cessation counselling at each clinic visit in accordance with US Public Health Service guidelines.
    Reference:
    Tonstad S et al. Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006;296:64-71.
  • Key Point:
    The primary end point was the rate of continuous abstinence (CA) for the double-blind treatment phase, confirmed by exhaled CO testing.1,2
    Background:
    The study’s primary efficacy end point was the 12-week CA rate for weeks 13 through 24 of the double-blind, placebo-controlled treatment period. For the double-blind phase, the continuous abstinence rate was defined as the proportion of participants who reported no smoking (not even a puff) or use of any nicotine-containing products since the previous point of contact (clinic visit or telephone contact). This was confirmed at each visit by an exhaled carbon monoxide measurement of ≤10 ppm.1,2
    Key secondary end points included the rate of CA from week 13 through week 52, which was the end of the non-treatment follow-up period. Other measures included the 7-day point-prevalence of abstinence during the open-label period (weeks 0 through 12) and weeks 12 through 52. The 7-day point prevalence of abstinence was defined as a self-report of no smoking or use of other tobacco or nicotine-containing products in the previous 7 days, confirmed by an expired CO value ≤10 ppm at clinic visits.1,2
    References:
    Tonstad S et al. Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006;296:64-71.
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
  • Key Point:
    In participants who entered the 12-week double-blind treatment phase, 70.5% of those in the group that quit initially and continued on varenicline treatment remained continuously abstinent from smoking up to week 24.
    Background:
    The results of the double-blind randomized phase of the study showed that 70.5% of subjects that quit initially and then received varenicline for an additional 12 weeks were continuously abstinent during weeks 13 through 24 vs. 49.6% of patients treated with 12 weeks of varenicline followed by placebo. At week 52, 43.6% of subjects that had received varenicline 1 mg BID for weeks 1-24 vs. 36.9% of subjects that had received varenicline 1 mg BID for weeks 1-12, and placebo for weeks 13-24, were continuously abstinent. At both weeks 24 and 52, the results were statistically significant (p<0.001 and p=0.02, respectively).
    Reference:
    Tonstad S et al. Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006;296:64-71.
  • Key Point:
    The most frequent adverse events in the varenicline treatment phase are presented here. Nausea was reported by about one third of the subjects, although only ~3% discontinued treatment for this reason. In the double-blind randomized phase of the trial, reports of nausea were very infrequent and were similar in the varenicline and placebo groups.
     
    Reference:
    Tonstad S et al. Effect of maintenance therapy with varenicline on smoking cessation: A randomized controlled trial. JAMA 2006;296:64-71.
  • Key Point:
    Two recently published meta-analyses of various pharmacological smoking cessation therapies have included the varenicline trials and provide additional insight on how CHAMPIX compares to existing therapies.1,2 Based on the findings of these analyses, CHAMPIX provides the highest odds of successful long-term smoking cessation, approximately threefold at one year2, of all pharmacological interventions.
    Background:
    Additionally, in one of the meta-analysis, in the absence of a comparative trial, the authors conducted an indirect comparison of varenicline to NRT and suggested that “varenicline was superior to NRT at one year when compared to placebo controls (OR 1.66, 95% CI 1.17-2.36, p=0.004) or to all controls (OR 1.73, 95% CI 1.22-2.45, p=0.001).”1
    Reference:
    Wu P et al. Effectiveness of smoking cessation therapies: A systematic review and meta-analysis. BMC Public Health 2006;6:300.
    Cahill K et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2007;(1):CD006103.
  • Key Point:
    Varenicline at a dose of 1 mg BID can be safely taken for periods up to 1 year.1,2
    Background:
    Most adverse events were of mild or moderate intensity. Nausea was the most common AE, followed by sleep disturbances in the form of insomnia or abnormal dreams. These AEs rarely resulted in discontinuation of study medication.1,2
    References:
    Tonstad S. Varenicline for smoking cessation. Expert Rev Neurotherapeutics 2007;7:121-127.
    Williams KE et al. A double-blind study evaluating the long-term safety ofvarenicline for smoking cessation. Curr Med Res Opin 2007;23:793-801.
  • Key Point:
    CHAMPIX (varenicline tartrate) is indicated for smoking cessation in adults in conjunction with smoking cessation counselling.1
    Background:
    When prescribing CHAMPIX (varenicline tartrate), physicians also should provide patients with advice and support concerning their attempt at quitting smoking, as smoking cessation therapies appear to be more likely to be successful in conjunction with behavioural interventions.1,2 Patients must choose a date to quit smoking and initiate varenicline treatment 1-2 weeks before this date.1
    CHAMPIX (varenicline tartrate) is taken orally, with or without food, with titration according to the following schedule: an initial dose of one 0.5 mg tablet once daily for the first 3 days, then one 0.5 mg taken in the morning and one 0.5 mg tablet taken in the evening for the next four days up to day 7. After the first 7 days, the dose can remain at 0.5 mg bid or can be increased to one 1.0 mg tablet in the morning and one 1.0 mg tablet in the evening. Patients who cannot tolerate varenicline may have the dose lowered temporarily or permanently.1
    References:
    CHAMPIX Product Monograph, Pfizer Canada Inc., May 2010.
    O’Donnell DE et al. State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
  • Key Point:
    Pre-marketing clinical trials included approximately 2,300 patients treated for at least 12 weeks, approximately 700 for 6 months, and approximately 100 for one year.
    Background:
    In general, onset of adverse events was in the first few weeks of therapy and severity was generally mild to moderate. No differences were observed by age, race or gender with regard to the incidence of adverse reactions, although patient numbers in elderly, and in non-caucasian races were too limited to allow conclusions.
    Nausea was the adverse event with the highest incidence. For patients exposed to the maximum recommended dose of 1 mg BID following initial dosage titration, the incidence of nausea was 30%, compared with 16% in 0.5 mg BID and approximately 10% in placebo-treated patients. Nausea was generally described as mild to moderate and often transient; however, for some subjects, it was persistent throughout the treatment period. Initial dose titration was beneficial in reducing the occurrence of nausea.
    Reference:
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
  • To conclude, varenicline is a new and innovative smoking cessation aid specifically designed to help smokers who are motivated to quit. The full course of treatment is 12 weeks, with a recommended target quit date 1-2 weeks into treatment (the pivotal studies utilized a day 8 quit date). Those who successfully quit after an initial 12 weeks may pursue treatment for an additional 12 weeks to ensure greater success.1-4
    A support program has also been developed to help smokers throughout their quitting journey, as additional support and counselling increase the likelihood of success.1,2
    References:
    West R. Assessment of dependence and motivation to stop smoking. BMJ 2004;328:338-339.
    CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    Gonzales D et al. Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial. JAMA 2006;296:47-55.
    Jorenby DE et al. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: A randomized controlled trial. JAMA 2006;296:56-63.
  • Reference:
    Critchley J, Capewell S. Smoking cessation for the secondary prevention of coronary heart disease. Cochrane Database Syst Rev 2003(4):CD003041.
  • Key Point:
    Along with cholesterol and blood pressure reduction, quitting smoking is a critically important risk factor to manage in postponing or preventing CHD-related deaths.
    Background:
    This study by Unal and colleagues investigated the potential impact of population-based primary prevention measures (in healthy individuals) versus secondary prevention efforts of risk factor reduction in patients with CHD on cardiovascular health in England and Wales. They constructed a model that synthesized data on the number of CHD patients, use of specific treatments, trends in cardiovascular risk factors, and mortality benefits of specific risk factor changes in healthy people and in CHD patients. In the healthy population, the single largest factor contributing to the reduction in CHD mortality rates in 1981-2000 was quitting smoking. Over this time period, CHD mortality actually declined by 54%, and smoking prevalence fell by 35%. Quitting smoking resulted in the prevention or postponement of about 24,680 deaths – a substantially higher amount than the deaths prevented/postponed by cholesterol reduction (n=4710) and blood pressure reduction (n=7235).
    Reference:
    Unal B, Critchley JA, Capewell S. Modelling the decline in coronary heart disease deaths in England and Wales, 1981–2000: comparing contributions from primary prevention and secondary prevention. BMJ 2005;331:614.
  • Key Point:
    In order to overcome the chronic relapsing nature of nicotine addiction, it is important to implement a comprehensive approach to smoking cessation.1-4
    Background:
    Both pharmacological intervention and behavioural modification are pertinent components of a successful quit attempt. Indeed, the most effective methods of smoking cessation combine pharmacotherapy with advice and behavioural support.3,5
    References:
    O'Donnell DE et al.State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
    Jarvis MJ. ABC of smoking cessation: Why people smoke. BMJ 2004;328:277-279.
    Coleman T. ABC of smoking cessation. Use of simple advice and behavioural support. BMJ 2004;328:397-399.
    Rigotti NA. Treatment of tobacco use and dependence. N Engl J Med 2002;346:506-512.
    Hughes JR. New treatments for smoking cessation. CA Cancer J Clin 2000;50:143-151.
  • Key Point:
    Characteristics such as high level of dependence, low socioeconomic class, and living with someone who smokes are associated with a lower likelihood of quitting smoking.
    Background:
    The US Community Intervention Trial for Smoking Cessation (COMMIT) study followed 6,603 individuals who were current smokers in 1988 for 13 years. Participants completed detailed telephone surveys on tobacco habits (in 1988, 1993, and 2001) and were asked questions about methods and reasons for quitting smoking (in 1993 and 2001). Individuals who reported that they had not smoked for ≥6 months before completing the survey were categorized as former smokers. The investigators conducted a logistic regression analysis to assess the association between the characteristics of smokers and success of quitting smoking. They found that higher levels of nicotine dependence (assessed by cigarette count and time to first cigarette upon awakening) and living with at least 1 other smoker were both associated with a decreased likelihood of quitting smoking.1
    In the British Household Panel Survey, over 10,000 adults were interviewed, with approximately 30% reporting smoking cigarettes. Chandola and colleagues investigated socio-demographic factors among this population and their relation to successful smoking cessation. All the socio-demographic variables were significantly associated with quitting smoking. Respondents in the small employer, supervisor, and routine occupational classes were less likely to quit compared to professional respondents. In addition, those living in more deprived wards, having fewer educational qualifications, or lower household incomes were less likely to quit.2
    Kalman and colleagues reviewed the comorbidity of smoking with psychiatric (PD) and substance use disorders (SUD). They note that an important subset of refractory smokers are those with PD or SUD, among whom smoking rates exceed those in the general population by two- to fourfold. Among “ever smokers,” persons with PD or SUD are less likely to be former smokers than other smokers. Significantly lower quit rates are associated with several specific PD and SUD, including alcohol use disorder, bipolar disorder, major depression, and post-traumatic stress disorder.3
    References:
    Hyland A et al. Predictors of cessation in a cohort of current and former smokers followed over 13 years. Nicotine Tob Res 2004;6(Suppl3):S363–S369.
    Chandola T, Head J, Bartley M. Socio-demographic predictors of quitting smoking: how important are household factors? Addiction 2004;99:770-777.
    Kalman D, Morissette SB, George TP. Co-morbidity of smoking in patients with psychiatric and substance use disorders. Am J Addict 2005;14:106-123
  • Key Point:
    Every smoker should be advised to quit. Three types of non-pharmacologic interventions that are especially effective are practical counselling, social support as treatment, and social support outside of treatment.
    Background:
    Even brief intervention for quitting smoking can be effective, and every smoker should be advised to quit. Based on extensive research of published trials, the recommendations from the US Department of Health and Human Services Clinical Practice Guideline for treating tobacco use and dependence emphasize the importance of person-to-person interaction, finding that these treatments (eg, individual, group, or proactive telephone counselling) are consistently effective in helping smokers to quit.
    Not all approaches are appropriate for all smokers, and clinicians should, when possible, direct smokers to the best form of treatment available depending on the individual needs of the patient and access to available resources. There is a dose-dependent relationship between the intensity of tobacco-dependence counselling and its effectiveness. Nevertheless, whether intervention is brief or intensive, the same 3 types of counselling and behavioral therapies are especially effective and should be used with all patients attempting to quit: 1) practical counselling, which comprises problem solving and skills training; 2) social support as part of treatment; and 3) social support outside of treatment.
    References:
    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.
    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.
  • Key Point:
    In any practice, a systematized strategy for helping patients quit smoking may result in greater reductions in smoking prevalence over the long-term.
    Background:
    An organized practice that has a systematized strategy for implementing smoking cessation interventions in patients has the potential to result in greater reductions in smoking prevalence over the long-term.1 Conducting an office inventory for tobacco intervention can help a physician determine whether or not a patient who smokes is managed appropriately. Physicians should establish how often and by whom tobacco use in patients is evaluated and should systematize this step. Tobacco use information should be readily available in a patient’s chart. The office should have a valid tool to assess the willingness of patients to quit smoking and a designated person who asks patients about their motivation to quit. Other key factors are staff and physician training, the availability of information to patients on tobacco treatment options, patient follow-up, and management of patients who relapse after attempting to quit. Recognizing the demands on a physician’s time, some steps of the 5A model can be delegated, such as the initial query as to smoking status, assisting the smoker to quit, and arranging follow-up.2
    References:
    Prochazka AV. New developments in smoking cessation. Chest 2000;117(Suppl1):169S–175S.
    Swartz SH, Hays JT. Office-based intervention for tobacco dependence. Med Clin North Am 2004;88:1623–1641.
  • Key Point:
    The “5 A’s” — asking about tobacco use, advising smokers to quit, assessing their willingness to stop smoking, assisting them to quit, and arranging follow-up — comprise an effective model for the physician or other healthcare professionals to treat tobacco use and dependence.1
    Background:
    Physicians and other healthcare professionals need to proactively engage with patients to provide medical interventions to improve quitting success rates. The Canadian Thoracic Society recommends that physicians use an intervention model incorporating the “5 A’s”: ask, advise, assess, assist, and arrange follow-up. The first step is to identify and document tobacco use for every patient at every visit by asking them about their tobacco use. For current smokers, the next steps are to first advise them to quit in a clear, strong, and personalized manner, and then assess their willingness to do so at this time. Those who are or who become willing to quit should be assisted with quitting, including counselling and pharmacotherapy (unless special circumstances do not allow for pharmacologic intervention). Finally, the last step is to arrange an initial follow-up with smokers soon (preferably within 1 week) after the quit date, and to develop a follow-up plan comprising more visits or telephone contacts to promote the success of the attempt.1-3
    References:
    Fiore MC et al. Effective tobacco dependence treatment. JAMA 2002;288:1768-1771.
    O'Donnell DE et al.State of the art compendium: Canadian Thoracic Society recommendations for the management of chronic obstructive pulmonary disease. Can Respir J 2004;11(SupplB):3B-59B.
    Optimal Therapy Initiative (University of Toronto). Smoking cessation guidelines: How to treat your patient's tobacco addiction, 2000.
  • Key Point:
    The Fagerström test is a commonly used tool to assess nicotine dependence and has been widely used in clinical trials.
    References:
    Heatherton TF et al. The Fagerström test for nicotine dependence: a revision of the Fagerström tolerance questionnaire. Br J Addict 1991;86:1119-27.
    Heart and Stroke Foundation. The Fagerström Test for Nicotine Dependence. Available at: http://ww2.heartandstroke.ca/DownloadDocs/PDF/Fagerstrom Test.pdf. Accessed January 10, 2007.
  • Key Point:
    The second step in the 5A model involves strongly urging all tobacco users to quit.
    Background:
    The second step in an intervention incorporating the 5A model is to advise all current smokers to quit in a clear, strong, and personalized manner. Examples of clear statements include, “I think it is important for you to quit smoking now, and I can help you,” and “Cutting down while you are ill is not enough.”
    The following is a representative example of a strong statement: “As your clinician, I need you to know that quitting smoking is very important to protecting your health now and in the future. The clinic staff and I will help you.” Personalization of the advice includes tying tobacco use to current health/illness, its social and economic costs, motivation level/readiness to quit, and/or the impact of tobacco use on children and others in the household.
    Reference:
    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.
  • Key Point:
    Assisting the smoker with quitting is the next step in the 5A model.
    Background:
    The fourth step in the 5A intervention model is to assist those who are or who become willing to quit, including appropriate counseling and pharmacotherapy (unless special circumstances do not allow for pharmacologic intervention).
    Assisting willing patients involves making a quit plan by setting a date to stop smoking, telling family and friends (to elicit understanding and support), anticipating challenges with quitting (withdrawal symptoms), and removing tobacco products from the environment. Practical counseling is an important part of cessation assistance. The physician should emphasize total abstinence, draw from previous experience with quitting, help the smoker to understand triggers and challenges, encourage abstinence from alcohol, and explain the importance of having housemates and family members quit smoking as well.
    The physician should provide a supportive clinical environment and offer assistance in the development of a social network to support the quit attempt. In regard to pharmacotherapy, use of approved medications should be recommended, except in special circumstances, with an explanation of how these drugs may increase smoking cessation success and reduce withdrawal symptoms. The provision of supplementary materials should accompany all quit attempts. These materials are available from federal agencies, nonprofit agencies, or local/state health departments. They should be culturally/racially/educationally/age appropriate for the patient and readily available at every clinician’s workstation.
    Reference:
    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.
  • Key Point:
    Lastly, follow-up contact should be arranged as part of the 5A model.
    Background:
    The final step in the 5A model is to arrange an initial follow-up with the patient soon (preferably within 1 week) after the quit date and a second follow-up within a month of quitting. This is important in supporting the patient and promoting the success of the attempt. After the second follow-up contact, additional follow-ups occur as needed, either in person or via telephone.
    During the follow-up visit, the clinician should congratulate success. If tobacco use has occurred, review the circumstances and elicit a recommitment to complete abstinence. Remind the patient that a lapse can be used as a learning experience. The clinician should help the patient identify problems already encountered and anticipate challenges in the immediate future. Pharmacotherapy use and issues associated with quitting should be assessed during the follow-up meeting, and consideration of provision or referral to more intensive treatment should be given.
    Reference:
    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.
  • Key Point:
    The effectiveness of non-pharmacologic treatment counselling increases with intensity. Even a brief amount of physician advice increases the likelihood of being abstinent.
    Background:
    Session length was categorized based upon the maximum amount of time the clinician spent with a smoker addressing tobacco dependence in a single contact. These levels of person-person contact were compared to no contact (e.g. self-help only). The data indicates that there is a dose-response relationship between session length and abstinence rates whereby higher intensity counselling produced higher abstinence rates than either minimal or low intensity counselling.
    Reference:
    Fiore MC et al. Clinical Practice Guideline: Treating Tobacco Use and Dependence: 2008 Update. US Department of Health and Human Services. Public Health Service. May 2008. Available at: http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pdf
  • Smoking cessation presentation dr. tsui - abbotsford, june 6, 2012

    1. 1. Conflict Disclosure Info • Speaker: Winston Tsui • “Understanding Smoking Cessation Treatment Options and Their Accessibility To Your Patients”. • Financial Disclosure: • Speaking engagements/honorarium: Pfizer, Servier, Bayer, Boeringher
    2. 2. Disclosure • I have full editorial control over the content of this presentation and wish to advise and that it may contain content that that is not consistent with the approved Canadian Product Monographs.
    3. 3. Objectives • Review the latest clinical literature in smoking cessation and establish the burden of smoking and its diseases as a serious health matter • Understand tobacco dependence mechanisms and recognize the fundamental problem of smoking as an addiction • Outline and apply the most current and effective non-pharmacological and pharmacological treatment strategies in a systematic approach in terms of screening, diagnosis, intervention and follow-up of patients who smoke • Create an awareness and recognize smoking as a major modifiable risk factor in the reduction of chronic diseases while addressing challenging questions surrounding safety of smoking cessation therapies
    4. 4. Burden of Disease
    5. 5. Tobacco use is the leading preventable cause of death in the world. World Health Organization: The World Health Report 2003 Courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    6. 6. Tobacco will kill Over 175 million People Worldwide Between 2005 and 2030 http://www.cancer.org/downloads/AA/TobaccoAtlas3/TA3_Chapt_10.pdf Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    7. 7. Tobacco-Related Deaths are Increasing1,2 Deaths Attributable to Tobacco Tobacco may kill one billion people in the 21st century, unless young people avoid taking up smoking and current users quit.2 Deaths (in Millions) 1 1 1 The 1950 death rate in developing countries was negligible. ckay J, Eriksen M. The Tobacco Atlas, 2002. ckay J, Eriksen M. The Tobacco Atlas, 2006.
    8. 8. Smoking Prevalence in Canada: 17% ~ 5 Million Smokers Newfoundland & Labrador 20% B.C. 15% Alberta 18% Manitoba 18% Saskatchewan 22% Ontario 16% Québec 20% New Brunswick 21% Health Canada. Canadian Tobacco Use Monitoring Survey – Ages 25+ from Annual 2009. http://www.hc-sc.gc.ca/hl-vs/tobac-tabac/research-recherche/stat/ctums-esutc_2007-eng.php PEI 18% Nova Scotia 19%
    9. 9. The Impact of Smoking on Canadians Almost 5 Million Canadians Smoke1 ♦ Smoking is the #1 preventable cause of death in Canada.2 – 22% of all deaths in Canada are attributable to smoking 2 – More than 45,000 Canadians die due to smoking each year2† lculation based on data from the year 1998. Health Canada. Canadian Tobacco Use Monitoring Survey 2005, Summary of Annual Results. Makomaski Illing EM, Kaiserman, Can J Public Health 2004;95:38-44.
    10. 10. Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    11. 11. Smoking Saturates Nicotinic Receptors MRI: Magnetic resonance image kBq/mL 9 0 0.0 Cigarette 0.1 Cigarette Brody AL. Arch Gen Psychiatry 2006;63:907-915. 0.3 Cigarette 1.0 Cigarette 3.0 Cigarette Nondisplaceable
    12. 12. What’s in a Cigarette? ♦ Tobacco smoke: ≥ 4000 chemicals1, ≥ 50 carcinogenic2 Chemicals in Tobacco Smoke1 Also Found In… Acetone Butane Arsenic Cadmium Carbon monoxide Toluene Paint stripper Lighter fluid Ant poison Car batteries Car exhaust fumes Industrial solvent ♦ Nicotine is responsible for the addiction, but other chemicals are also involved.2 ♦ Smoking cigarettes with lower tar and nicotine provides no health benefit.2 1. World Health Organization. Tobacco: deadly in any form or disguise, 2006. 2. Health Canada. What’s in Cigarette smoke?, August 2005.
    13. 13. Why Quit? Potential Lifetime Health Benefits of Quitting Smoking1-2 Cardiovascular heart disease (CHD) risk is similar to never smokers Lung cancer risk is 30-50% that of continuing smokers Stroke risk returns to the level of people who have never smoked at 5-15 years post-cessation 1. CDC. Surgeon General Report 2004: American Cancer Society. Guide to Quitting Smoking. 2. US Department of Health & Human Services. The Health Benefits of Smoking Cessation: A Report of the Surgeon General. 1990. 15 years 10 years 5 years 1 year 3 months Cessation CHD: excess risk is reduced by 50% among ex-smokers Lung function may start to improve with decreased cough, sinus congestion, fatigue, and shortness of breath
    14. 14. Tobacco Dependence Mechanisms
    15. 15. Mechanism of Action of Nicotine in the Central Nervous System ♦ Nicotine binds β2 β2 preferentially to nicotinic α4 β2 α4 acetylcholine (nACh) receptors in the central nervous system; the primary is the α4β2 nACh receptor in the Ventral α4β2 Tegmental Area (VTA) Nicotinic Receptor ♦ After nicotine binds to the α4β2 nACh receptor in the VTA, it results in a release of dopamine in the Nucleus Accumbens (nAcc), which is believed to be linked to reward Foulds J. Int J Clin Pract 2006;60:571-576.
    16. 16. FOREBRAIN Dopamine BRAIN STEM α4ß2 receptors Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    17. 17. “Smokers smoke to maintain relative constancy of nicotine, dopamine and other neurotransmitter levels.” Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    18. 18. The Cycle of Nicotine Addiction ♦ Nicotine binding causes an increase in dopamine release 1 ♦ Dopamine gives feelings of pleasure and Nicotine calmness 2 ♦ The dopamine decrease between cigarettes leads to withdrawal symptoms of irritability and stress 3,4 ♦ A smoker craves nicotine to release more dopamine to restore pleasure and calmness 2,3 1. 2. 3. 4. Foulds J. Int J Clin Pract 2006;60:571-576. Fagerstrom K. Drugs 2002;62(Suppl2):1-9. Jarvis MJ. BMJ 2004; 328:277-279. Rigotti NA. N Engl J Med 2002;346:506-512. Dopamine
    19. 19. Quitting Smoking: May be a Protracted Journey ♦ The majority of smokers are motivated to quit 1 ♦ Most try to quit without pharmacological assistance 2 ♦ 87% of current smokers have tried to quit smoking at least once before 3 ♦ 19% of smokers report craving is the most common reason why quitting smoking is considered difficult 4 ♦ Relapse is common 5 ♦ Many smokers make multiple attempts to quit 1. 2. 3. 4. 5. ♦ Only ~ 5% succeed without assistance Hughes JR. CA Cancer J Clin 2000;50:143-151. Anthenelli RM. Clin Neurosci Res 2005;5:175-183. Pfizer Canada Inc., Data on file. 2006. O'Donnell DE et al.Can Respir J 2004;11(SupplB):3B-59B. Fiore MC et al.JAMA 2002;288:1768-1771.
    20. 20. Tobacco Dependence and Environmental Reinforcement ♦ Pharmacologic effects – Nicotine as an addictive drug ♦ Non-pharmacologic effects – Environmental/social stimuli associated with smoking play a role in reinforcing nicotine dependence Caggiula AR et al.Psychol Behav 2002;77:683–687.
    21. 21. Withdrawal Syndrome: a Combination of Physical and Psychological Conditions, Making Smoking Hard to Treat1,2 Withdrawal Syndrome Irritability, frustration, or anger Anxiety Restlessness or impatience Insomnia/sleep disturbance Increased appetite or weight gain Dysphoric or depressed mood Difficulty concentrating 1. Diagnostic and Statistical Manual of Mental Disorders, IV-TR. Washington, DC: APA; 2006. 2. West RW et al. Fast Facts: Smoking Cessation. 1st ed. Oxford, United Kingdom. Health Press Limited, 2004.
    22. 22. Withdrawal Symptoms from Stopping Smoking Incidence Increased appetite 70% Restlessness 60% Depression 60% Irritability/aggression 50% Craving for nicotine 70% Poor concentration 60% Sleep disturbance 25% Lightheadedness 10% 0 1 2 3 4 5 Duration (weeks) Jarvis MJ. BMJ 2004;328:277-279. 6 7 8 9 10 or more
    23. 23. Select Withdrawal Symptoms Over Time Placebo Impatience 1.5 Nicotine Gum Irritability/Anger 1.5 1.0 0.5 de s u d A nae M t j er oc Sl a w r dhi W a t 1.0 0.5 0.0 0.0 1 2 3 4 5 6 7 8 1 9 10 Postcessation Weeks 3 4 5 6 7 8 9 10 Postcessation Weeks Anxiety/Tension Excessive Hunger 1.5 1.5 1.0 1.0 0.5 de s u d A nae M t j r oc Sl a w r dhi W a t 2 0.5 0.0 0.0 1 2 3 4 5 6 7 8 Postcessation Weeks 9 10 1 2 3 4 5 6 7 8 9 10 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.
    24. 24. Probability of Dependence After Trying a Substance at Least Once Tobacco Heroin Cocaine Alcohol Stimulants Anxiolytics Cannabis Analgesics Inhalants 32% 23% 17% 15% 11% 9% 9% 8% 4% Stahl’s Essential Psychopharmacology, 3 rd ed. 2008 Courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    25. 25. Pharmacological Smoking Cessation Treatment Approaches
    26. 26. Pharmacotherapy for Tobacco Dependence 1-4 3 First-Line Therapies: ♦ Nicotine replacement therapy (NRT) – Long-acting -- Patch – Short-acting -- Gum, Inhaler, Lozenges ♦ Bupropion SR ♦ Varenicline 1. 2. 3. 4. O'Donnell DE et al.Can Respir J 2004;11(SupplB):3B-59B. Foulds J. Int J Clin Pract 2006;60:571-576. Challenge Quit to win. Pharmacological Aids. February 20, 2007. CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    27. 27. Effectiveness and abstinence rates for various medications and medication combinations compared to placebo at 6-months postquit (n = 83 studies)a Medication Placebo # of Estimated odds Estimated arms ratio (95% C.I.) abstinence rate 80 1.0 Monotherapies 13.8 (95% C.I.) Varenicline (2 mg/day) 5 3.1 (2.5–3.8) 33.2 (28.9–37.8) Nicotine Nasal Spray 4 2.3 (1.7–3.0) 26.7 (21.5–32.7) High-Dose Nicotine Patch ( > 25 mg) (Included 4 2.3 (1.7–3.0) 26.5 (21.3–32.5) both standard or long-term duration) Long-Term Nicotine Gum (> 14 weeks) 6 2.2 (1.5–3.2) 26.1 (19.7–33.6) Varenicline (1 mg/day) 3 2.1 (1.5–3.0) 25.4 (19.6–32.2) Nicotine Inhaler 6 2.1 (1.5–2.9) 24.8 (19.1–31.6) Clonidine 3 2.1 (1.2–3.7) 25.0 (15.7–37.3) Bupropion SR 26 2.0 (1.8–2.2) 24.2 (22.2–26.4) Nicotine Patch (6–14 weeks) 32 1.9 (1.7–2.2) 23.4 (21.3–25.8) Long-Term Nicotine Patch (> 14 weeks) 10 1.9 (1.7–2.3) 23.7 (21.0–26.6) Nortriptyline 5 1.8 (1.3–2.6) 22.5 (16.8–29.4) Nicotine Gum (6–14 weeks) 15 1.5 (1.2–1.7) 19.0 (16.5–21.9) Go to www.surgeongeneral.gov/tobacco/gdlnrefs.htm for the articles used in this meta-analysis Fiore MC et al. US Department of Health and Human Services. Public Health Service. May 2008. a
    28. 28. Effectiveness of smoking cessation interventions Comparison # studies # participants Pooled Odds Ratio (95% CI) Non-pharmacological intervention Self-help1 vs. no intervention 11 >13,000 1.24 (1.07-1.45) Individual counseling2 vs. minimal behaviour intervention 21 >7,000 1.56 (1.32-1.84) Physician advice3 vs. no advice 17 >13,000 1.74 (1.48-2.05) Group counseling4 vs. no intervention 7 815 2.17 (1.37-3.45) Pharmacological intervention NRTs5,6 vs. control 39,503 1.77 (1.66-1.88) Bupropion SR7 vs. placebo 1. 2. 3. 4. 5. 6. 7. 103 19 >4,000 2.06 (1.77-2.40) Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(3):CD001118. Lancaster T. Stead LF. Cochrane Database Syst Rev 2005;(2):CD001292. Lancaster T, Stead LF. Cochrane Database Syst Rev 2004;(4):CD000165. Stead LF, Lancaster T. Cochrane Database Syst Rev 2005;(4):CD001007. Silagy C et al. Cochrane Database Syst Rev 2004;(3):CD000146. Stead L, Lancaster T. Int J Epidemiol 2005;34:1001–1003. Hughes JR et al. Cochrane Database Syst Rev 2004;(4):CD000031.
    29. 29. Nicotine Replacement Therapy (NRT) ♦ NRT has been shown to be safe and effective in helping people stop using cigarettes 1 ♦ Delivers nicotine that binds to the nAChR receptors 1 ♦ NRTs does not deliver nicotine to the circulation as rapidly as smoking; is delivered via the venous system 2 1. American Heart Association website. 2. Sweeney CT et al.CNS Drugs 2001;15:453-467.
    30. 30. 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) 18 16 Plasma Nicotine Concentration (μg/L) Transdermal patch 14 12 10 8 6 4 2 0 0 Sweeney CT et al. CNS Drugs 2001;15:453-467. 10 20 30 40 50 60 70 80 90 100 110 120 Time post-administration (minutes)
    31. 31. Efficacy of Nicotine Replacement Therapy (NRT) Trials (n) Participants (n) Pooled RR (95% CI) Gum 53 19,090 1.43 (1.33–1.53) Patch 41 18,237 1.66 (1.53–1.81) Nasal spray 4 887 2.02 (1.49–3.73) Inhaler 4 976 1.90 (1.36–2.67) Tablets/lozenges 6 3109 2.00 (1.63–2.45) Patch and inhaler 1 245 1.07 (0.57–1.99) Choice of NRT product 2 496 2.26 (1.26–4.05) 110 43,040 1.58 (1.50–1.66) Comparison Any NRT vs. control Stead L et al. Cochrane Database Syst Rev. 2008; Jan 23(1):CD000146.
    32. 32. 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 dopamine 2,3 – Non-competitive inhibition of α3β2 and α4β2 nicotine receptors4,5 Zyban® is a registered trademark of the GlaxoSmithKline Group of Companies and is used by Biovail under license. 1. Product Monograph. 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. Pr
    33. 33. Comparison of Nicotine Replacement Therapy (NRT) and Bupropion SR Therapy for Quitting Smoking1 ♦ Only cessation study comparing NRT and antidepressant therapy 2 Placebo (n=160) Buproprion SR (n=244) Nicotine Patch (n=244) Bupropion SR + Patch (n=245) * * *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.
    34. 34. Bupropion SR for Tobacco Dependence Trials (n) Participants (n) Pooled OR† (95% CI) Bupropion SR alone vs. Placebo 19 6443 2.06 (1.77–2.40) Bupropion SR plus nicotine patch vs. placebo 2 728 1.60 (1.09–2.34) All bupropion SR vs. placebo 21 7171 1.99 (1.73–2.30) Comparison OR= odds ratio 1. Hughes J, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2004;(4):CD000031. 2. Hughes JR, Stead LF, Lancaster T. Nortriptyline for smoking cessation: a review. Nicotine Tob Res 2005;7:491–499. † 17
    35. 35. Varenicline: An α4β2 Nicotinic Acetylcholine Receptor Partial Agonist and Antagonist ♦ ACTIVITY 1: Partial agonist – Varenicline binds to the receptor, partially stimulating dopamine release ♦ ACTIVITY 2: Antagonist – Because varenicline is bound to the receptor, it prevents the binding of nicotine Activation of the central nervous mesolimbic dopamine system is believed to be the neuronal mechanism underlying reinforcement and reward experienced upon smoking CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    36. 36. Varenicline Comparative Studies Design1,2 Treatment phase Non-treatment phase Varenicline 1 mg BID† Bupropion 150 mg BID† Placebo Screening visit Baseline randomization Week 12 Treatment Period Week 52 Non-pharmacological Follow-up B L W 1 W 2 W 3 W 4 W 5 W 6 W 7 W 8 W 9 W 10 W 11 W 12 W 13 W W 16 20 W 24 W 28 W 32 W W 36 40 W 44 W 48 W 52 C C C C C C C C C C C C C C T C T T C C T C Randomization Target quit date Titrated during Week 1. L = Baseline; W = Week; C = Clinic visit; T = Telephone contact 1. Gonzales D et al.JAMA 2006;296:47-55. 2. Jorenby DE et al.JAMA 2006;296:56-63. T T Two identically designed Phase 3 efficacy trials Varenicline 1.0 mg BID vs placebo or Bupropion SR150 mg BID 12 weeks of active treatment followed by 40 weeks of non-pharmacologic follow-up
    37. 37. Varenicline Comparative Studies Primary/Secondary End Points ♦ Primary End Point1-3 – 4-Week Continuous Quit Rate (CQR), defined as the proportion of individuals who maintained complete abstinence from cigarette smoking and other nicotine use during the last 4 weeks (weeks 9 through 12) of the treatment period – Abstinence was defined as self-report of no smoking (not even a puff of a cigarette) and confirmed by exhaled CO measurements ≤10 ppm ♦ Key Secondary End Point1-3 – Continuous Abstinence (CA) rate from weeks 9 through 52 – Smoking Abstinence Point Prevalence verified by carbon monoxide level at 7 days 1. Gonzales D et al.JAMA 2006;296:47-55. 2. Jorenby DE et al.JAMA 2006;296:56-63. 3. CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    38. 38. Varenicline Comparative Studies 4-Week Continuous Quit Rates Weeks 9–121,2 50 45 40 35 30 25 20 15 10 5 0 44.0% † Study 2/Jorenby et al.2 †p<0.001 vs. bupro. and placebo ‡p<0.001 vs. placebo 29.5% ‡ 17.7% Varenicline 1 mg BID n=352 Bupropion SR 150 mg BID n=329 Placebo n=344 Odds ratio varenicline vs. placebo: 3.85; p<0.001 varenicline vs. bupropion SR: 1.93; p<0.001 1. Gonzales D et al.JAMA 2006;296:47-55. 2. Jorenby DE et al.JAMA 2006;296:56-63. Continuous quit rate Week 9-12 (%) Continuous quit rate Week 9-12 (%) Study 1/Gonzales et al.1 50 45 40 43.9% 35 † 30 25 20 15 10 5 0 Varenicline 1 mg BID n=344 †p<0.001 vs. bupro. and placebo §p=0.001 vs. placebo 29.8% § 17.6% Bupropion SR 150 mg BID n=342 Placebo n=341 Odds ratio varenicline vs. placebo: 3.85; p<0.001 varenicline vs. bupropion SR: 1.90; p<0.001
    39. 39. Varenicline Comparative Studies Continuous Abstinence (CA) Rates Weeks 9–521,2 Study 1/Gonzales et al.1 Study 2/Jorenby et al.2 20 25 21.9% †‡ 15 † p=0.057 vs. bupropion SR ‡ p<0.001 vs. placebo §p<0.001 vs. Placebo 16.1% § 10 8.4% 5 0 Varenicline 1 mg BID n=352 Bupropion SR 150 mg BID n=329 Placebo n=344 Odds ratio varenicline vs. placebo: 3.09; p<0.001 varenicline vs. bupropion SR: 1.46; p=0.057 1. Gonzales D et al.JAMA 2006;296:47-55. 2. Jorenby DE et al.JAMA 2006;296:56-63. Continuous abstinence rate Week 9-52 (%) Continuous abstinence rate Week 9-52 (%) 25 23.0% 20 ¶ †† 15 ¶p=0.004 vs. bupropion SR †† p<0.001 vs. placebo ‡‡p<0.08 vs. Placebo 14.6% ‡‡ 10 10.3% 5 0 Varenicline 1 mg BID n=344 Bupropion SR 150 mg BID n=342 Placebo n=341 Odds ratio varenicline vs. placebo: 2.66; p<0.001 varenicline vs. bupropion SR: 1.77; p=0.004
    40. 40. Varenicline Maintenance of Abstinence (Extended Therapy) Study Design Non-treatment Double-blind phase follow-up phase Open-label phase Varenicline 1 mg BID Varenicline 1 mg BID (titrated) Placebo Baseline Week 12 Week 24 Double-blind treatment Open-label treatment B L C W 1 C W 2 C W 3 C W 4 C W 5 C W 6 C W 7 C W 8 C Target quit date L = Baseline; W = Week; C = Clinic visit; T = Telephone contact Tonstad S et al.JAMA2006;296:64-71. W 10 C W 12 C W 13 C W 14 C W 16 C Randomization W 20 C W 24 C Week 52 Non-pharmacologic follow-up (Double-blind) W 25 C W 26 T W 28 C W 32 T W 36 C W 40 T W 44 C W 48 T W 50 C Study goal: To investigate the benefit of an additional 12-week dosing for subjects who achieved abstinence during the last 7 days of open-label varenicline treatment (Week 12)
    41. 41. Varenicline Maintenance of Abstinence Study Primary/Secondary End Points ♦ Primary End Point1,2 – Carbon monoxide (CO)-confirmed continuous abstinence (CA)† rate from Week 13 through 24 (double-blind treatment phase) ♦ Key Secondary End Point1,2 – CA rate from Week 13 through 52 ♦ Other Measure1 – 7-day point-prevalence of abstinence, during open-label phase and from week 12 to week 52 The proportion of individuals who maintained complete abstinence for this specified time period. Determined on a weekly basis, abstinence was defined as self-report of no smoking (not even a puff of a cigarette) and confirmed by exhaled CO measurements ≤10 ppm. † 1.Tonstad S et al.JAMA 2006;296:64-71. 2.CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    42. 42. Maintenance of Abstinence (Extended Therapy) in Quitters that had Previously Received 12 Weeks of Varenicline Therapy 1210 subjects who quit after 12 weeks of varenicline treatment were then randomized to an additional 12 weeks. p<0.001 vs. placebo † OR: varenicline vs. placebo 2.48, p<0.001 In the subsequent 28-week nontreatment follow-up of those who participated in the double-blind phase of the study, the continuous abstinence rate for weeks 13 through 52 was 43.6% in the CHAMPIX-CHAMPIX group vs. 36.9% in the CHAMPIX-placebo group (p=0.02) Tonstad S et al. JAMA 2006;296:64-71
    43. 43. Varenicline Maintenance of Abstinence Study: Adverse Events Most Frequent AEs (Open-label Varenicline) Open label Varenicline n % Newly emerging – Double blind Varenicline Placebo n % n % Nausea Mild Moderate Severe 645 452 162 31 33.5 70.1 25.1 4.8 7 5 2 0 1.2 4 4 0 0 0.7 Insomnia 377 19.6 16 2.7 17 2.8 Headache 304 15.8 17 2.8 12 2.0 Abnormal dreams 276 14.3 6 1.0 0 0.0 Tonstad S et al. JAMA 2006;296:64-71.
    44. 44. Comparison of Pharmacological Interventions for Smoking Cessation Comparison # studies # participants Pooled OddsRatio (95% CI) Pharmacological interventions NRTs vs. control 103 39,503 1.77 (1.66-1.88) Bupropion SR vs. placebo 19 >4,000 2.06 (1.77-2.40) CHAMPIX vs. placebo 4 2,023 3.22 (2.43-4.27) CHAMPIX vs. bupropion SR 3 1,622 1.66 (1.28-2.16) CHAMPIX vs. NRT (all controls) Indirect comparison Not Applicable 1.73 (1.22-2.45) For NRT and bupropion SR data: Cochrane Database Syst Rev 2004, 2005; Stead L, Lancaster T. Int J Epidemiol 2005;34:1001-1003. For CHAMPIX pooled data: Cochrane Database Syst Rev 2007; Wu P et al.BMC Public Health 2006,6:300.
    45. 45. Long-Term Safety Study Conclusions ♦ Varenicline at a dose of 1 mg bid, can safely be taken for periods up to one year ♦ AEs affecting tolerability were mostly related to gastrointestinal symptoms or sleep disturbances ♦ Nausea was the most common AE, but was rarely rated as severe and infrequently resulted in discontinuation of study medication ♦ Sleep disturbances, in the form of insomnia or abnormal dreams, also rarely resulted in discontinuation of study medication 1. Tonstad S. Expert Rev Neurotherapeutics 2007;7:121-127. 2. Williams KE et al. Curr Med Res Opin 2007;23:793-801.
    46. 46. Varenicline Summary ♦ An innovative smoking cessation therapy believed to have simultaneous partial agonist and antagonist activities at the α4β2 nACh receptor1 – Clinical significance is not fully confirmed1 ♦ Demonstrated significantly superior continuous quit rates for weeks 9 through 12 vs. bupropion SR (Zyban®) and placebo in 2 pivotal head-to-head clinical trials:2,3 – ~4X greater odds of quitting smoking with varenicline (CHAMPIX) vs. placebo (odds ratio=3.85, p<0.001; odds ratio=3.85, p<0.001)2,3 – ~2X greater odds of quitting smoking with varenicline (CHAMPIX) vs. bupropion SR (odds ratio=1.93, p<0.001; odds ratio=1.90, p<0.001)2,3 ♦ Established safety and tolerability profile in approximately 2,300 treated smokers1 Pr Zyban® is a registered trademark of the GlaxoSmithKline Group of Companies and is used by Biovail under license. 1.CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007. 2.Gonzales D et al.JAMA 2006;296:47-55. 3.Jorenby DE et al.JAMA 2006;296:56-63.
    47. 47. CHAMPIX (Varenicline) Indication and Dosing Information ♦ Indicated for smoking cessation treatment in adults in conjunction with smoking cessation counselling ♦ Treatment period is 12 weeks ♦ An additional course of 12 weeks of treatment may be considered for patients who have successfully quit at the end of 12 weeks ♦ Varenicline is supplied for oral administration in 2 strengths: 0.5 mg and 1.0 mg ♦ After the first week of titration, there are two dosing options: the dose can remain at 0.5 mg twice a day or go up to 1.0 mg twice a day. Days 1 – 3: 0.5 mg once daily Days 4 – 7: 0.5 mg twice daily Day 8 – End of treatment: 0.5 mg twice daily OR 1 mg twice daily CHAMPIX Product Monograph, Pfizer Canada Inc., May 2010
    48. 48. Varenicline Safety Information ♦ Established safety and tolerability profile assessed in approximately 2,300 subjects ♦ In general, onset of adverse events occurred in the first few weeks of therapy and severity was generally mild to moderate ♦ The most commonly observed adverse events associated with varenicline (>5% and twice the rate seen in placebo-treated patients) were nausea, abnormal dreams, constipation, flatulence, and vomiting Adverse event Varenicline 0.5 mg BID n=129 Nausea Abnormal dreams Constipation Flatulence Vomiting Varenicline 1.0 mg BID n=821 16% 9% 5% 9% 1% Placebo n=805 30% 13% 8% 6% 5% 10% 5% 3% 3% 2% ♦ Discontinuation rate due to nausea was only 2.7% (vs. 0.6% for placebo) CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007.
    49. 49. CHAMPIX (Varenicline) Key Points to Keep in Mind: ♦ Identify patients who are motivated to quit smoking, since motivated quitters are more likely to succeed1,2 ♦ Prescribe a 12-week course of CHAMPIX treatment2 ♦ Have patients set a target quit date 1-2 weeks into treatment 2-4 – The pivotal studies utilized a day 8 quit date3,4 ♦ Reassess patients after 12 weeks – For those who were successful, an additional course of 12 weeks may be considered to help them stay quit2 1.West R. BMJ 2004;328:338-339. 2.CHAMPIX Product Monograph, Pfizer Canada Inc., January 2007. 3.Gonzales D et al.JAMA 2006;296:47-55. 4.Jorenby DE et al.JAMA 2006;296:56-63.
    50. 50. Cost of Champix ♦ Starter pack (week 1 & 2): $42 ♦ Continuation: $47 ♦ One month: $94 ♦ Cigarettes (1 ppd) for 1 month: $261 - $287
    51. 51. Cardiovascular Concerns ♦ In 2011, the FDA issued an advisory that varenicline may increase the risk of adverse cardiovascular events in patients with known CVD. ♦ Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Rigotti NA et al. Circulation. 2010;121(2):221. ♦ Varenicline vs placebo: nonfatal myocardial infarction (2 vs 0.9 %), need for coronary revascularization (2.3 vs 0.9%), and a new PAD (1.4 vs 0.9%), not statistically significant ♦ Overall and patients treated with varenicline had a lower rate of cardiovascular mortality (0.6 versus 1.4%) also not statistically significant. ♦ This same trial showed that varenicline is effective for smoking cessation in patients with CVD. ♦ The FDA suggested that the known benefits of varenicline be weighed against potential harms in patients with CVD.
    52. 52. Cardiovascular Concerns ♦ Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. Singh S et al. CMAJ. 2011;183(12):1359. ♦ meta-analysis of 14 randomized placebo-controlled trials of Varenicline evaluated 8216 smokers with no or stable CVD ♦ Treatment with varenicline resulted in an increased risk of a composite measure of adverse cardiovascular events including myocardial ischemia, arrhythmia, heart failure, sudden death, or cardiovascular-related death (1.06 versus 0.82 percent, OR 1.72, 95% CI 1.09-2.71). ♦ Although the absolute increase in events of 0.24%.
    53. 53. Cardiovascular Concern ♦ Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis ♦ BMJ 2012; 344 doi: 10.1136/bmj.e2856 (Published 4 May 2012) BMJ 2012;344:e2856 ♦ 22 trials, 2 with active CVD, 11 with Hx CVD ♦ 0.63% vs. 0.47%
    54. 54. ♦ Over the long term, even in a higher risk population of patients with stable CVD, the benefits of smoking cessation likely outweigh potential short-term harms of varenicline. ♦ However, this increase in risk may be important in choosing between medical therapies for smoking cessation in patients at increased risk of cardiovascular events.
    55. 55. People who quit smoking after a heart attack or cardiac surgery reduce their risk of death by 36% Cochrane Database of Systematic Reviews 2003;4:CD003041 Slide courtesy of Andrew Pipe, CM, MD, LLD(Hon), DSc(Hon)
    56. 56. Model of Deaths Prevented or Postponed Through Risk-Factor Reduction Coronary Heart Disease Deaths in England Unal B et al.BMJ 2005;331:614.
    57. 57. Neuropsychiatric effects ♦ In 2008 FDA from post marketing reports suggested patients should be monitored for neuropsychiatric symptoms including changes in behavior, hostility, agitation, depressed mood, suicidal ideation, and suicide attempts. ♦ Vareniciline was responsible for 90 percent of 13,243 reported cases of suicidal/self-injurious behavior or depression, followed by buproprion (7 percent), and nicotine replacement (3 percent) ♦ Retrospective data collection that could be affected by over-reporting of adverse events due to extensive media coverage of varenicline.
    58. 58. Neuropyschiatric Affects ♦ In contrast, a pooled analysis of 10 randomized placebo-controlled trials in 5096 smokers found no association between varenicline and incidence of psychiatric disorders or psychiatric adverse events ♦ Smokers themselves have an increased risk of suicidal behavior, and similar neuropsychiatric symptoms, also occur with nicotine withdrawal. ♦ Benefits of stopping smoking outweigh the uncertain but potential risk of using varenicline in most patients. ♦ Need to take a careful psychiatric history prior to prescribing the drug, avoiding it in smokers with a history of suicidal ideation or a current unstable psychiatric status.
    59. 59. BC Smoking Cessation Program Effective September 30th, 2011, Pharmacare launched the B.C. government’s Smoking Cessation Program which is intended to help eligible B.C residents stop smoking or stop using other tobacco products by assisting them with the cost of smoking cessation aids. ♦ The program offers coverage for two treatment options: 1. 2. prescription smoking cessation drugs or non-prescription nicotine replacement therapy (NRT) products.
    60. 60. Patient eligibility criteria ♦ To be eligible for nicotine replacement therapy program, patients must have valid, active Medical Services Plan (MSP) coverage ♦ To be eligible for PharmaCare coverage of prescription smoking cessation drugs, patients must be registered for Fair PharmaCare or covered by one of the following PharmaCare plans: – Permanent Residents of Licensed Residential Care Facilities (Plan B) – Recipients of B.C. Income Assistance plan (Plan C) – No-Charge Psychiatric Medication plan (Plan G) Source: BC Smoking Cessation Program-Information for Prescribers. Retrieved Oct 21, 2011 from http://www.heath.gov.bc.ca/pharmacare/stop-smoking/mid-intro.html
    61. 61. Coverage Details ♦ Each calendar year, eligible B.C. residents may receive one or the other of the following: – Coverage for ONE of the designated prescription smoking cessation drugs for a single continuous course of treatment lasting up to 12 consecutive weeks (84 consecutive days). The actual coverage patients receive depends on the rules of their PharmaCare plan*. OR – 100% coverage for ONE of the designated nicotine replacement therapy products for a single continuous course of treatment lasting up to 12 consecutive weeks (84 consecutive days). Source: BC Smoking Cessation Program-Information for Prescribers. Retrieved Oct 21, 2011 from http://www.heath.gov.bc.ca/pharmacare/stop-smoking/mid-intro.html
    62. 62. Coverage details continued.. Handling requests for prescription drugs – key points ♦ You do NOT need to obtain Special Authority for an initial 12-week course of treatment with bupropion (Zyban®) and varenicline (Champix®). ♦ Patients do NOT need to register for coverage through HealthLink BC for the prescription drugs. Handling requests for NRTs – key points ♦ Patients DO have to register for the smoking cessation program by phoning HealthLink BC at 8-1-1 before they can obtain their NRT products. ♦ You do NOT need to write a prescription for either Habitrol® NRT patches or Thrive™ NRT gum. Patients can have these over-the-counter products fully covered under the B.C. Smoking Cessation program without a prescription. Source: BC Smoking Cessation Program-Information for Prescribers. Retrieved Oct 21, 2011 from http://www.heath.gov.bc.ca/pharmacare/stop-smoking/mid-intro.html
    63. 63. For More Information… ♦ Visit the Ministry of health website at www.health.gov.ca/pharmacare/stopsmoking/ for more information about the BC Smoking Cessation Program
    64. 64. Non-Pharmacological Smoking Cessation Treatment Approaches
    65. 65. A Comprehensive Approach to Smoking Cessation ♦ Nicotine addiction has two main components: – the pharmacological action of nicotine – behavioural factors 1-3 ♦ Current pharmacotherapies approximately double the odds of quitting 4,5 ♦ Advice and support increase the chances of success 4,5 1. 2. 3. 4. 5. Jarvis MJ. BMJ 2004;328:277-279. Coleman T. BMJ 2004;328:397-399. Rigotti NA. N Engl J Med 2002;346:506-512. Hughes JR. CA Cancer J Clin 2000;50:143-151. O'Donnell DE et al.Can Respir J 2004;11(SupplB):3B-59B. Most effective methods of smoking cessation combine pharmacotherapy with advice and support 2,4
    66. 66. Why May Some Smokers Need More Help to Quit ? ♦ Higher level of dependence 1 – Cigarettes per day – Time to first cigarette upon waking ♦ Living with a current smoker 1 ♦ Fewer educational qualifications 2 ♦ Lower socioeconomic class 2 ♦ Co-morbid psychiatric disorders 3 1. Hyland A et al.Nicotine Tob Res 2004;6(Suppl3):S363-S369. 2. Chandola T et al.Addiction 2004;99:770-777. 3. Kalman D et al.Am J Addict 2005;14:106–123.
    67. 67. Non-pharmacologic Approaches Advice and Support 1-3 ♦ All smokers should be: – Advised to quit – Offered assistance ♦ Non-pharmacologic approaches can be helpful – Strategic, tactical advice – ‘medicine management’ – Social support as part of treatment – Securing social support outside of treatment 1. Pisinger C et al.Prev Med 2005;40:278-284. 2. Fiore MC et al.Clinical Practice Guideline: Treating Tobacco Use and Dependence. US Department of Health and Human Services. Public Health Service; June 2000. 3. National Institute for Health and Clinical Excellence. Brief interventions and referral for smoking cessation in primary care.
    68. 68. Office-based Strategies for Helping Patients Quit Smoking ♦ A systematic approach to identifying smokers1 ♦ Sharing responsibility within a practice setting 2 – Ask – office staff can identify smoking status – Advise, Assist – physician’s core tasks – Assist and Arrange – office staff “Make the most efficient use of time and resources” 1. Prochazka AV. Chest 2000;117(Suppl1):169S–175S. 2. Swartz SH, Hays JT. Med Clin North Am 2004;88:1623–1641.
    69. 69. Brief Tobacco Intervention Using the 5 A’s ♦ Identify and document tobacco use ASK ♦ In a clear, strong, personalized manner, urge smoker to quit ADVISE ♦ Is the smoker ready to make a quit attempt? ASSESS ♦ Use counselling and pharmacotherapy to help him/her quit ASSIST ♦ Schedule follow-up contact ARRANGE – Preferably within 1 week after the quit date MC et al. Effective tobacco dependence treatment. JAMA 2002;288:1768-1771
    70. 70. Baseline assessment of the smoking status: The Fagerström Test for Nicotine Dependence 1,2 Questions Answers 1. How soon after you wake up do you smoke your first cigarette? Points After 60 minutes 0 31-60 minutes 1 6-30 minutes 2 Within 5 minutes 3 Yes 1 No 0 The 1st in the morning 1 All others 0 10 or less 0 11-20 1 21-30 2 31 or more 3 5. Do you smoke more frequently during the first hours after awakening than during the rest of the day? Yes 1 No 0 6. Do you smoke even if you are so ill that you are in bed most of the day? Yes 1 No 0 2. Do you find it difficult to refrain from smoking in places where it is forbidden? 3. Which cigarette would you hate most to give up? 4. How many cigarettes per day do you smoke? Dependence scores 0-2 Very low 3-4 Low 5 Medium 6-7 High 1. Heatherton TF et al.Br J Addict 1991;86:1119-27. 2. Heart and Stroke Foundation. The Fagerström Test for Nicotine Dependence. 8-10 Very high
    71. 71. 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) MC et al. US Department of Health and Human Services. Public Health Service. June 2000.
    72. 72. The “5As”: Assist in Quit Attempt ♦ For the patient willing to make a quit attempt, use counselling and pharmacotherapy – Provide practical counselling (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 e MC et al. US Department of Health and Human Services. Public Health Service. June 2000.
    73. 73. 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 MC et al. US Department of Health and Human Services. Public Health Service. June 2000.
    74. 74. Smoking Cessation Effectiveness Increases with Treatment Intensity Meta-analysis (2000): Effectiveness of and estimated abstinence rates for various intensity levels of session length (n = 43 studies)a Level of Contact No Contact Number of Arms Estimated Odds Ratio (95% CI) 1.0 30 Estimated Abstinence Rate† (95% CI) 10.9 Minimal Counseling (less than 3 minutes) 19 1.3 (1.01 – 1.6) 13.4 (10.9 – 16.1) Low Intensity Counseling (3 to 10 minutes) 16 1.6 (1.2 – 2.0) 16.0 (12.8 – 19.2) Higher Intensity Counseling (more than 10 minutes) 55 2.3 (2.0 – 2.7) 22.1 (19.4 – 24.7) The abstinence rate is defined as the proportion of participants who reported no smoking. Fiore MC et al. US Department of Health and Human Services. Public Health Service. May 2008. † a Go to www.surgeongeneral.gov/tobacco/gdlnrefs.htm for the articles used in this meta-analysis

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