Smoking Cessation

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Smoking Cessation Addictive Behaviour

• Andy McEwen, PhD
• UCL and Cancer Research UK
• Smoking cessation update meeting
• Dundee, 25th October 2007

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Conflict of interest statement

• I undertake consultancy for, and receive
  hospitality and travel funds from, companies
  developing and manufacturing medications to aid
  smoking cessation
• I am lead author of a book for stop smoking
  advisors (Manual for Smoking Cessation) and for
  clients (The Stop Smoking Handbook)
• I am on a patent for a novel nicotine inhalation
  device

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Outline

• Addictive behaviour (tobacco dependence)
• Varenicline (Champix) update
• Q A
• With thanks to Robert West, Alex Bobak Gay
  Sutherland

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Addiction and dependence (1)

• Dependence is not really about thisHumans as
  rational decision makers
• Smoking is an adult pursuit and should remain a
  matter for informed and adult choice
• (Tobacco Manufacturers Association UK, Smoking
  and children, 1997)

• The drinker

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Addiction and dependence (2)

• But has elements of thisHumans as emotional
  decision makers
• Our decisions are influenced by our needs and
  emotions.
• Self-labels and perceptions are important sources
  of motivation.

Smoke-scream
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Addiction and dependence (3)

• And thisHumans as animals
• Operant conditioning
• Habits result from experience of reward and
  punishment
• Classical conditioning
• Stimuli take on motivational value by being
  associated with other stimuli
• Drive theory
• Behaviours derive from biological imperatives

www.michaelmain.com/addict.jpg
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Addiction and dependence (4)

• Not much of thisPsychoanalysis
• Our experiences and behaviour stem from
  interactions and imbalances between different
  parts of our psyche
• But some of thisPersonality traits
• We vary in propensity to impulsiveness, anxiety
  etc.
• And thisSocial experience
• Our experiences and behaviours derive from the
  way we construct our world

www.fantavier.net
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Addiction and dependence (5)
Addictions are activities that are given an
unhealthy priority because of a disordered
motivational system
Dependence refers to the nature of that disorder.
It varies from individual to individual and
behaviour to behaviour
The key concept is motivational balance
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Addiction and dependence (6)

• Key elements of PRIME theory
• The structure of the motivational system is
  comprised of five levels (PRIME)
• The focus on the moment
• How dispositions change and the unstable mind
• The importance of identity and its role in
  self-control

www.primetheory.com
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Addiction and dependence (7)
The human motivational system
Plans (intentions)
Evaluations (beliefs)
External environment (stimuli, information)
Internal environment (percepts, drives,
emotional states, arousal, ideas, frame of mind)
Motives (wants etc.)
Internal stimulation
Impulses (urges etc.)
Responses
External stimulation
Flow of influence through the system
www.primetheory.com
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Addiction and dependence (8)
Example Inhibition of smoking
Not smoking
Inhibition
Cues/triggers
Desire not to smoke
Need not to smoke
Anticipated praise
Anticipated disgust, guilt or shame Fears about
health
Anticipated self-respect
Positive evaluations of not smoking
Reminders
Non-smoker identity
Beliefs about benefits of not smoking
Plan not to smoke
Nicotine dependence also involves impairment of
impulse control mechanisms undermining response
inhibition
www.primetheory.com
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Addiction and dependence (9)
The importance of the moment
Evaluations, wants, emotional states, impulses
and plans are only present when triggered and
have no influence when not present

• Everything we think, feel or do is a reaction to
  what happens
• We only think about things when we are prompted
  to do so
• The way that we think or feel about things
  depends to some degree on the current
  circumstances
• Not thinking about things is an important method
  of reducing dissonance

www.primetheory.com
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Addiction and dependence (10)
How dispositions change
Environmental forces
Critical periods points where the chreods fork
Waddingtons epigenetic landscape
Deep chreods small forces will not lead to
escape the system will settle back once they are
removed but if the system is on a cusp a small
force will tip it into a new path
www.primetheory.com
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Addiction and dependence (11)

• And the unstable mind
• The fly-by-wire brain the brain has evolved to
  be inherently unstable
• this makes it highly adaptable and creative
• but it needs constant balancing input to keep it
  from veering off in unwanted directions
• This is similar to modern fighter aircraft whose
  airframes are designed to be unstable and require
  constant input from computers to keep them on
  course

www.primetheory.com
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Addiction and dependence (12)
Balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Major event
Balancing inputs
Lack of balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Balancing inputs
Trigger stimulus
www.primetheory.com
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Addiction and dependence (13)
Identity

• Identity is a very important source of motives
  it is the foundation of personal norms that shape
  and set boundaries on our behaviour

Self-control

• Self-control is a cornerstone of behaviour
  change. The moment-to-moment wants and needs
  arising from that must be strong enough to
  overcome impulses, wants and needs coming from
  other sources
• The exercise of self-control is effortful it
  requires and uses up mental resources

www.primetheory.com
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Addiction and dependence (14)
Conclusion

• Addiction is a disorder of motivation
• Elements Plans, Evaluations, Motives, Impulses
  Responses
• Influenced by the internal external environment
• The moment is important
• The 3 Ts

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Varenicline (Champix) update (1)

• Brain Reward Pathway(Mesolimbic Dopamine System)
• Within seconds of inhaling, nicotine activates
  a4ß2 nicotinic receptors located in the Brain
  Reward Pathway
• This leads to an immediate and large dopamine
  release in the nucleus accumbens

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NucleusAccumbens(NAcc)
NIC
VentralTegmentalArea(VTA)
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Varenicline (Champix) update (3)

• Regular smoking results in neuro-adaptation in
  response to the nicotine

leading to a 300 increase in density of
nicotinic receptors
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Varenicline (Champix) update (4)
Foulds (2006) Int. J Clin. Prac
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Varenicline (Champix) update (5)

• Partial agonist, specifically designed to bind
  with high affinity selectivity to the a4ß2
  receptor
• So it mimics nicotine and stimulates moderate
  dopamine release reducing the severity of
  craving and withdrawal symptoms
• But also partially blocks the receptors so
  nicotine from cigs. can not stimulate the receptor

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Varenicline (Champix) update (6)
Varenicline - partial nicotine agonist
Part blocking Reduces the pleasurable effects of
smoking and potentially the risk of full relapse
after a temporary lapse1-4

• Part Stimulating
• Relieves craving and withdrawal symptoms1-3

1. Coe JW. J Med Chem 2005 483474-3477. 2.
Gonzales D et al. JAMA 2006 29647-55. 3.
Jorenby DE et al. JAMA 2006 29656-63. 4.
Foulds J. Int J Clin Pract 2006 60571-576.
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Varenicline (Champix) update (7)
Clinical studies

• Two Identical Comparator Studies
• Varenicline vs. bupropion vs placebo
• Extended Therapy Study
• Effect of 12 vs 24 wks of varenicline vs.
  placebo
• Long-Term Safety Study
• Varenicline vs. placebo for 1 yr

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Varenicline (Champix) update (8)

• Smokers in the comparator studies
• 1/3 given Champix, 1/3 given Zyban 1/3 given
  Placebo (double-blind)
• Drug taken for 12 weeks with f-up to 1 year
• Plus 10 mins weekly behavioural support for 12
  weeks educational booklet
• Smoking 21 cigs/day
• Been smoking for 25 years
• 85 had made previous quit attempts

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Varenicline (Champix) update (9)
12 week quit rates Primary endpoint (9-12
continuous abstinence) Pooled Analysis,
comparator studies 1 2 (n2,045)
n692
n669
n684
varenicline vs. bupropion OR 1.87 (95 CI 1.40,
2.34), plt0.0001 varenicline vs. placebo OR
3.69 (95 CI 2.88, 4.72), plt0.0001
1. Gonzales DH et al. Presented at 12th SRNT,
15-18th Feb, 2006, Orlando, Florida. Abstract
PA9-2.
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Recruitment to Abstinence
Varenicline (Champix) update (10)
Some evidence that in first 4 weeks, smokers on
Champix are being recruited into abstinence
(ie. had smoked after the Quit Date but became
abstinent later)
Gonzaleset al. JAMA. 200629647-55.
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Varenicline (Champix) update (11)
Varenicline 24 wks Varenicline 12 wks
P0.02 OR 1.34
70.5
43.6
of Patients
49.6
36.9
Week
Tonstad S, et al. JAMA. 200629664-71.
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Varenicline (Champix) update (12)

• Withdrawal Symptoms
• Compared to placebo, Champix significantly
  reduced
• Depressed mood
• Irritability, frustration or anger
• Anxiety
• Difficulty concentrating

Gonazales D et al. JAMA 200629647-55 Jorenby
DE et al. JAMA 200629656-63.
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Varenicline (Champix) update (13)

• Effects on smoking of Varenicline
• Compared to placebo, smoking while taking Champix
  reduced
• Reward Satisfaction
• Enjoyment of respiratory tract sensation

Gonazales D et al. JAMA 200629647-55 Jorenby
DE et al. JAMA 200629656-63.
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Varenicline (Champix) update (14)

• Why wasnt Champix compared with NRT?
• In US where trials conducted, Zyban was the
  market leader main medication not NRT
• Zyban is slightly more effective than NRT
• NICE will have seen these results and taken them
  into account in their guidance
• A multi-centre NRT comparison study has now been
  completed but not yet published

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Varenicline (Champix) update (15)
Adverse events on varenicline compared with
placebo
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Varenicline (Champix) update (16)
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Varenicline (Champix) update (17)

• What about nausea?
• Warn before prescribing
• Usually self limiting
• Take with food or water
• Adjust dose
• Can use anti-emetics prochlorperazine (Stemetil)

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Varenicline (Champix) update (19)

• Pharmacological Properties
• Steady-state reached within 4 days
• Elimination half-life of 24 hours
• No significant hepatic effects
• No clinically meaningful drug interactions

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Varenicline (Champix) update (20)
Quit date

• Clients who cannot tolerate adverse effects may
  have the dose lowered to 0.5mg bd
• Clients should stop smoking in their second week
  of treatment with varenicline

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Varenicline (Champix) update (21)

• Who Can Use It?
• Contraindicated
• Hypersensitivity to Varenicline
• Not Recommended
• Pregnancy
• Under 18 yrs
• End stage renal disease

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Varenicline (Champix) update (22)

• Cautions for Use
• Severe renal disease as primarily excreted via
  kidneys (reduce to 1mg daily)
• Epilepsy (not tested)
• Psychiatric illness (not tested)
• Quitting smoking may exacerbate underlying
  condition
• Breast feeding
• Do not combine with NRT or Zyban

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Varenicline (Champix) update (23)
LifeRewards Behavioural Support Programme (Free
of Charge)
LifeREWARDS Programme Virtual coach providing
11 advice and helpful tips 24/7 Specifically
designed to complement treatment with
varenicline Use batch code on pack to access
web-site
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Varenicline (Champix) update (24)
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Varenicline (Champix) update (25)

• varenicline was superior to NRT and bupropion
  in achieving continuous abstinence
• Varenicline is recommended, within its licensed
  indications
• .should normally be provided in conjunction
  with counselling and support
• .but if such support is refused, or not
  available, this should not preclude treatment
  with varenicline

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Varenicline (Champix) update (26)
NHS STOP SMOKING SERVICES Service and Monitoring
Guidance October 2007/08

• Services should be tailored to include the
  provision of NICE recommended smoking cessation
  medicines varenicline (Champix), bupropion
  (Zyban) and NRT.
• Smoking cessation medicines should be made as
  widely and readily available as possible.

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Varenicline (Champix) update (27)
Statistics on NHS Stop Smoking Services in
England, April 2007 to June 2007 (Q1 Quarterly
Report)

• Champix was the most successful smoking
  cessation aid in helping people quit
• Of those who used Champix 67 successfully quit,
  compared with 55 who received bupropion only,
  and 50 who received NRT

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Smoking Cessation Service Research Network
(SCSRN)www.scsrn.org
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