Treating Tobacco Use Disorder - BC Society of Respiratory Therapists

Treating Tobacco Use
Disorder
Dr Milan Khara MBChB CCFP ABAM
Medical Lead
VGH Smoking Cessation Clinic
Clinical Assistant Professor
Faculty of Medicine, UBC
milan.khara@vch.ca

Disclosure
I have received unrestricted research funding/grants,
speaker’s honoraria, consultation fees or product from
the following in the previous 12 months:
Health Canada
Interior Health Authority
Provincial Health Services Authority
Northern Health Authority
Pfizer
Johnson and Johnson
Janssen
Ottawa Heart Institute
TEACH (Centre for Addiction and Mental Health)
Government of Nunavat
Smoking Prevalence in Canada: 17%
4.9 Million Smokers
Newfoundland
& Labrador
19%
B.C.
14%
Alberta
18%
Manitoba
19%
Saskatchewan
19%
Health Canada. Canadian Tobacco Use Monitoring Survey 2011,
Summary of Annual Results.
Ontario
16%
Québec
20%
PEI
19%
Nova Scotia
18%
New
Brunswick
19%
What's New in Tobacco Control?

Plain Packaging
Prevalence of Smoking: Psychiatric
and Substance Use Disorders
From Kalman, Morissette and George (2005), Am. J. Addict., 14: 106-123
Disease Burden
 The leading preventable cause of death in
Canada
 37,000 smoking attributable deaths per year
 1 in 2 smokers die prematurely from a
smoking related illness
 44% of tobacco consumption by the mentally
ill
Doll R, Peto R. et al. Mortality in relation to smoking: 50 years' observations on male
British doctors. BMJ. 2004
Lasser K, Boyd JW, Woolhandler S et al. (2000), Smoking and mental illness. A
population-based prevalence study. JAMA
Canadian Cancer Society/National Cancer Institute of Canada. (2005). Canadian
Cancer Statistics 2005.
Smoking Is a Known Cause
of Multiple Diseases
Cardiovascular
• Ischemic heart disease
(#2 preventable
cause of death)
• Stroke/vascular dementia
• Peripheral vascular disease
• Abdominal aortic aneurism
Cancer
• Lung (#1 preventable
cause of death)
• Oral cavity/pharynx
• Laryngeal
• Esophageal
• Stomach
• Kidney
• Bladder
• Cervical
Respiratory
• COPD (#3 preventable
cause of death)
• Community-acquired
pneumonia
• Poor asthma control
Active smoking and
second-hand smoke
Reproductive
Second-hand smoke
Other
• Increased risk of:
• Lung cancer
• Heart disease
• Worsen lung disease
•
• In infants/children:
• Middle-ear infections
• Worsens asthma
• Linked to SIDS
•
Adverse surgical outcomes/
wound healing
• Reduced bone density
• Hip fractures
• Cataract
• Peptic ulcer disease
• Exacerbation of diabetes
Increased risk of MS in genetically
susceptible individuals
• Erectile dysfunction
• Reduced fertility
• Pregnancy
complications
• Low birth weight
• SIDS (infants)
• Strabismus
(eye disorder in infants)
COPD = chronic obstructive pulmonary disease; SIDS = sudden infant death syndrome; MS = multiple sclerosis
7
Fagerström K. Drugs. 2002; 62(Suppl 2):1-9; Leung GM et al. Arch Pediatr Adolesc Med 2004; 158(7):687-93; Mackay J, Eriksen M. The Tobacco Atlas. Second Ed. Atlanta, GA: American Cancer Society; 2006; Simon KC et al. Neurology 2010;
74(17):1365-71; Teo KK et al. Lancet 2006; 368(9536):647-58; Torp-Pedersen T et al. Am J Epidemiol 2010; 171(8):868-75; US Department of Health and Human Services. News Release, June 27, 2006. Available at:
http://archive.hhs.gov/news/press/2006pres/20060627.html. Accessed: July 29, 2010; Weitzman M et al. Circulation 2005; 112(6):862-9.
7
Treating tobacco is a gold standard
treatment
Intervention
Outcome
NNT
Statins
Prevent 1 death over 5 years
107
Aspirin
Prevent 1 MI over 5 years
118
Antihypertensive therapy
Prevent 1 stroke, MI, death over 1 year 700
Cervical cancer screening
Prevent 1 death over 10 years
1140
MD 5 min advice to stop smoking
Prevent 1 premature death
80
+ cessation medication
Prevent 1 premature death
38-56
+ behavioral support
Prevent 1 premature death
16-40
Anthorison, 2006, Ann Intern Med; McQuay & Moore, 2006, Bandolier; Gates 2001, Am Fam Phys; Cochrane Reviews by Stead, Bergeson, et al., 2008; Stead, Perera, et al. 2012; Stead &
Lancaster, 2012; Cahill et al., 2010; and USPSTF, 2009
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
 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.
Mechanism of Action of Nicotine in
the Central Nervous System

b2 b2
a4 b2 a4

Nicotine binds
preferentially to nicotinic
acetylcholine (nACh)
receptors in the central
nervous system; the
primary is the α4β2 nACh
receptor in the Ventral
Tegmental Area (VTA)
After nicotine binds to the
a4b2 α4β2 nACh receptor in the
NicotinicVTA, it results in a release
Receptorof dopamine in the
Nucleus Accumbens
(nAcc), which is believed
to be linked to reward
Foulds J. Int J Clin Pract 2006;60:571-576.
NRT vs. Smoking
US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update
10 Key Recommendations
1. Recognize tobacco dependence as a chronic disease
– Repeated intervention and multiple quit attempts may be
necessary
2. Document smoking status and willingness to quit on a
regular basis
3. Support every patient identified as willing to quit with
counselling and medications
– Tobacco dependence treatments work across a broad
range of populations
4. Understand that even brief tobacco dependence treatment
can be effective
5. Use individual, group, and telephone counselling
– More intense treatment increases effectiveness
– Practical tips on how to quit and providing social support as part
of treatment improves success rates
US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update
10 Key Recommendations (Continued)
6. Prescribe recommended cessation medications.
7. Combine counselling and effective medications, because this
results in higher quit rates than either alone.
8. Encourage the use of telephone quit lines, which are readily
accessible and effective.
9. Use “motivational interviewing” techniques to offer support for
those identified as not willing to quit.
10. For policymakers and medical insurers, understand that
tobacco dependence treatment is highly cost effective and
patients should be reimbursed for these treatments
Fiore MC, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline.
US Department of Health and Human Services. Public Health Service; May 2008. Available at:
www.surgeongeneral.gov/tobacco/default.htm.
Cochrane Systematic Reviews:
Non-Pharmacological Treatment for Smoking Cessation
Trials
(n)
Participants
(n)
Pooled OR†
(95% CI)
 Physician advice1
Brief vs. no advice (usual care)
Intensive vs. minimal advice
17
15
>13,000
>9,000
1.66 (1.42–1.94)
1.37 (1.20–1.56)
 Individual counseling2
vs. minimal behavior intervention
17
>6,000
1.56 (1.32–1.84)
 Group counseling3
vs. self-help
vs. no intervention
16
7
>4,000
815
2.04 (1.60–2.60)
2.17 (1.37–3.45)
 Proactive Telephone counseling4
vs. less intensive interventions
13
>16,000
1.41 (1.27–1.57)
 Self-help5
vs. no intervention
11
>13,000
1.24 (1.07–1.45)
Comparison
†OR=
odds ratio. Abstinence assessed at least 6-months following intervention.
1. Stead LF, Bergson G, Lancaster T. Cochrane Database of Syst Rev 2008;(2): CD000165. 2. Lancaster T, Stead LF. Cochrane Database Syst Rev
2005;(2):CD001292. 3. Stead LF, Lancaster T. Cochrane Database Syst Rev 2005;(4): CD001007. 4. Stead LF et al. Cochrane Database Syst Rev
2005;(4):CD002850. 5. Lancaster T, Stead LF. Cochrane Database Syst Rev 2005;(3):CD001118.
A Brief Smoking Cessation
Intervention
ASK:
ADVISE:
ASSESS:
ASSIST:
about tobacco use
every tobacco user to quit
assess readiness to quit
self-help material
pharmacotherapy
counselling/quit lines
ARRANGE: follow up or referral
Fiore MC et al. Treating Tobacco Use and Dependence: 2008
Update. Clinical Practice Guideline.U.S. Department of Health and
Human Services. Public Health Service. May 2008
Principles of Motivational Interviewing
 Express Empathy
 Develop Discrepancy
 Roll with Resistance
 Support Self Efficacy
Miller and Rollnick (1991)
US PHS Guideline – Treating Tobacco Use and Dependence: 2008 Update
First-line Pharmacotherapies for
Tobacco Dependence1
 Nicotine replacement therapy (NRT)
– Patch
– Gum
– Inhaler
– Nasal spray (Not available in Canada)
– Lozenges
 Antidepressant
– Bupropion SR
 Nicotinic acetylcholine receptor partial agonist
– Varenicline
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.
US PHS Guideline – Treating Tobacco Use and Dependence:
2008 Update Meta-analysis of First-line Smoking Cessation Pharmacotherapies1

Effectiveness and abstinence rates for various medications compared with
placebo 6 months after quitting
Est. Odds Ratio
(95% CI)
Est. Abstinence Rate
(95% CI)
1.0
13.8
Varenicline (2 mg/day)
3.1 (2.5–3.8)
33.2 (28.9–37.8)
Nicotine Nasal Spray
2.3 (1.7–3.0)
26.7 (21.5–32.7)
High-Dose Nicotine Patch (>25 mg)
2.3 (1.7–3.0)
26.5 (21.3–32.5)
Long-term Nicotine Gum (>14 weeks)
2.2 (1.5–3.2)
26.1 (19.7–33.6)
Varenicline (1 mg/day)
2.1 (1.5–3.0)
25.4 (19.6–32.2)
Nicotine Inhaler
2.1 (1.5–2.9)
24.8 (19.1–31.6)
Bupropion SR
2.0 (1.8–2.2)
24.2 (22.2–26.4)
Nicotine Patch (6–14 weeks)
1.9 (1.7–2.2)
23.4 (21.3–25.8)
Long-term Nicotine Patch (>14 weeks)
1.9 (1.7–2.3)
23.7 (21.0–26.6)
Nicotine Gum (6–14 weeks)
1.5 (1.2–1.7)
19.0 (16.5–21.9)
Medication
Placebo
Fiore MC, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline.US Department of Health and Human Services. Public Health Service; May 2008. Available at:
www.surgeongeneral.gov/tobacco/default.htm
Nicotine Replacement Therapy

Provides the body with sufficient nicotine to
help minimize w/d symptoms and cravings




Safe in CVS populations (Hubbard 2005)
Most effective when combined with “therapy”
Role in forced or temporary abstinence
“Off-label” use….
Nicotine replacement therapy for smoking cessation. LF Stead et al Cochrane Database of
Systematic Reviews 2008
Nicotine Patch
 24 hour continuous dose of nicotine
 21, 14 and 7mg patches (applied every 24 h)




Smoking 20+ cigarettes= 21mg patch to start
Smoking 10-20 cigarettes= 14mg patch to start
Smoking < 10 cigarettes= 7mg patch to start
“Off-label” dosing….
 Potential side effects:
Sleep disturbance or nightmares
Skin irritation
Nicotine Gum

Provides body with nicotine over
20-30 mins



Responds to the immediate urge to smoke
Oral Gratification
Potential Side Effects
– Upset stomach, hiccups
• Chewing too fast, review proper use of gum
Bupropion SR: MOA and Efficacy
Primary MOA: Blocks reuptake of dopamine1,2
Secondary MOA: Non-competitive inhibition of
nicotine receptors3,4


Originally designed to treat depression
Shown to double ones chances of quitting
compared to placebo
•
“Bupropion increases smoking abstinence rates
in smokers with schizophrenia, without
jeopardising their mental state" (Cochrane 2009)
1. Henningfield JE et al. CA Cancer J Clin 2005;55:281–299. 2. Foulds J et al. Expert Opin Emerg Drugs 2004;9:39–53.
3. Slemmer JE et al. J Pharmacol Exp Ther 2000;295:321–327. 4. Roddy E. Br Med J 2004;328:509–511.
21
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.
Cardiovascular and Neuropsychiatric
Risks of Varenicline


Retrospective study, UK GP database

Followed for 6 months for incident CVS and
neuropsychiatric events

“Varenicline NOT associated with an increased risk of
documented CVS events, depression or self harm when
compared with NRT…..
164,766 patients received: NRT, Buproprion or
Varenicline (registered for >12 months)
Kotz, Daniel et al. Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study. The Lancet Respiratory Medicine Sept. 2015
Varenicline and Schizophrenia (Williams
et al 2012)





12 week RCT, placebo controlled (2:1), 127 smokers

Suicidal ideation rates 6% v 7%

DSM IV schizophrenia/schizoaffective disorder
7 day point prevalence (CO confirmed)
Cessation rates: 12wk 19% v 4.7%, 24wk 11.9% v 2.3%
No significant changes in symptoms (including
mood/anxiety)
Conclusion: Varenicline was well tolerated, with no evidence of
exacerbation of symptoms, and was associated with significantly higher
smoking cessation rates versus placebo at 12 weeks. Our findings suggest
varenicline is a suitable smoking cessation therapy for patients with
schizophrenia or schizoaffective disorder
Williams J. et al, J Clin Psychiatry. 2012 Jul;73(7):1035
Varenicline and Depression: Anthanelli et
al 2013


Confirmed CAR 9-12: 35.9% v 15.6% (OR 3.35)
Confirmed CAR 9-24: 25.0% v 12.3% (OR 2.53)
 No difference in scores on psychiatric rating scales
 No difference in reported neuropsychiatric AE’s

“Varenicline may be a suitable smoking cessation
treatment for smokers with stable or past major
depression”
Anthanelli R et al September 2013 Annals of Internal Medicine
Varenicline Maintenance In
Schizophrenia and BPD: Evins at al 2014


247 smokers: 12 weeks open-label Varenicline


At week 52, abstinence rates were 60% v 19% (OR 4.6)

“no significant effect on psychiatric symptoms ratings or
adverse events”
87 abstinent smokers randomized to placebo or
Varenicline through to week 52
“….maintenance varenicline improved abstinence rates
after 1 year of treatment’
Maintenance Treatment With Varenicline for Smoking Cessation in Patients With Schizophrenia and Bipolar Disorder
Evins A. et al JAMA Jan 2014
Electronic Nicotine Delivery Systems
(ENDS)
Electronic Nicotine Delivery Systems
(ENDS)

“The USPSTF concludes that the current evidence is
insufficient to recommend ENDS for tobacco cessation in
adults… recommends that clinicians direct patients who
smoke tobacco to other cessation interventions with
established effectiveness and safety”
 “estimates show e-cigarettes are 95% less harmful than
normal cigarettes, and when supported by a smoking
cessation service, help most smokers to quit tobacco
altogether.”
Siu, AL, . Behavioral and Pharmacotherapy Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015
McNeil A et al. E-cigarettes: an evidence update. Public Health England. August 2015
.
Electronic Nicotine Delivery Systems
(ENDS)

E-cigarettes…
– Are not currently marketed as cessation products at all
– Are not regulated or approved for sale in Canada
– Have not been fully evaluated for their efficacy as smoking
cessation therapies
– Have not been fully evaluated for their safety
• Formaldehyde-releasing molecules can be formed2
1. Sweanor D. Disease Interrupted: Tobacco Reduction and Cessation. Els et al. (Ed.); 2014;
2. Jensen RP, et al. N Engl J Med 2015;372:392-4;
Potential Effects of Smoking Marijuana

Severe pain or severe arthritis are the most commonly
cited reasons for medicinal cannabis use
– “Medical marijuana” has never been recommended by any
rheumatology group worldwide for rheumatic conditions

Smoking of cannabis is not medically recommended due
to the dangers of polycyclic aromatic hydrocarbons, tar,
and carbon monoxide
– Plasma concentrations of THC achieved by smoking are
extremely variable
Fitzcharles MA, et al. Arthritis Care Res 2014;66:797-801.
Most Harmful
least
regulated
Some Harm, some
regulation
Different Nicotine
“delivery systems”
Least Harmful, most
regulated
32
BC Smoking Cessation Program
 BC Smoking Cessation Program since Sept 2011
 155,000 people served ($27 million)
 12 weeks per year of NRT (patch or gum) OR
Varenicline /Zyban

Consider SA for extension/change
VGH Smoking Cessation Clinic
milan.khara@vch.ca
VGH Smoking Cessation Clinic
Smoking & Suicide Risk
P<.001
5
Relative riska
4.3
4
3
2.5
2
1
1.4
1.0
0
Never smokers
Ex-smokers
1-14 (n=1333)
15 (n=2241)
Cigarettes/day: current smokers
aAdjusted
for time period, age, alcohol, and marital status
Miller et al (2000) Am J Public Health 90(5): 768-773
Changes in mental health after smoking
cessation: systematic review

Investigate change in mental health after cessation v
continuing to smoke

Studies that assessed mental health before and after
cessation

“Smoking cessation is associated with REDUCED
depression, anxiety and stress…IMPROVED positive
mood and quality of life...effect equal for those with
psychiatric disorders as without…”
Taylor, Gemma et al. Change in mental health after smoking cessation: systematic review and meta-analysis BMJ 2014; 348 :g1151
Smoking Cessation and CYP 1A2

“polyaromatic hydrocarbons” induce CYP 1A2

Effects many medications eg Clozapine, Olanzapine,
Quetiapine

Monitor dosing up to 4 weeks post cessation/reduction
 “Caffeinism”