Download quitting smoking - International Quitline Institute

Nancy Rigotti, MD
Treatment Review:
Overview of the Evidence Base
for Tobacco Dependence Treatment
10/09/2011
OVERVIEW

Why is tobacco treatment necessary for global
tobacco control?

Why do smokers keep smoking?

What smoking cessation treatments are effective?

Behavioral

Pharmacological

Role of health care providers
WHY TREATMENT MATTERS

Tobacco use is the #1 preventable cause of death

Stopping tobacco use reduces health risks

Tobacco prevention works slowly
CESSATON vs. PREVENTION
WHY TREATMENT MATTERS

Tobacco use is the #1 preventable cause of death

Stopping tobacco use reduces health risks

Tobacco prevention works slowly

Tobacco use is an addictive disorder

Tobacco treatment aids tobacco control policies
overall (and vice versa)
MPOWER Report
World Health Organization – 2008
 M onitor tobacco use and tobacco control policy
 P rotect people from tobacco smoke
 O ffer help to quit tobacco use
 W arn about the dangers of tobacco
 E nforce bans on tobacco advertising, promotion
 R aise taxes on tobacco
OVERVIEW

Why is tobacco treatment necessary for global
tobacco control?

Why do smokers keep smoking?

What smoking cessation treatments are effective?

Behavioral

Pharmacological

Role of health care providers
WHY DO SMOKERS KEEP SMOKING?
 Pharmacologic nicotine dependence
DOPAMINE
WHY DO SMOKERS KEEP SMOKING?
 Pharmacologic nicotine dependence
→ Craving (nicotine “hunger”)
→ Nicotine withdrawal symptoms







Irritability, anger, impatience
Restlessness
Difficulty concentrating
Insomnia
Anxiety
Depressed mood
Increased appetite
WHY DO SMOKERS KEEP SMOKING?
 Pharmacologic nicotine dependence
 Psychological factors
•
•
Cues (meals, alcohol, other smokers)
Coping with stress, emotions (anger)
WHY DO SMOKERS KEEP SMOKING?
 Pharmacologic nicotine dependence
 Psychological factors
 Psychiatric co-morbidity
•
•
•
Depression
Schizophrenia
Substance abuse
THE CHALLENGE FOR TREATMENT

We have effective treatments, but…

We need better treatments

We need to deliver the treatments we have
to more of the smokers who need them
OVERVIEW

Why is tobacco treatment necessary for global
tobacco control?

Why do smokers keep smoking?

What smoking cessation treatments are effective?

Behavioral

Pharmacological

Role of health care providers
LIMITATION OF OUR EVIDENCE

The evidence about treatment comes mostly
from studies done in high-income countries

Few trials have been done in middle- or lowincome countries


Less awareness of health risks
Fewer have tried to quit and failed

Biology is relatively constant

Cultural context varies by country
SMOKING CESSATION METHODS
2008 US Public Health Service Guidelines
 Effective treatments

Counseling

Pharmacotherapy

Combination - better than either one alone
 More is better but brief intervention works
 Treating tobacco is highly cost-effective
COUNSELING – Content
 Smokers who want to quit
 Cognitive-behavioral counseling
 Social support
 Encourage medication use and adherence
 Smokers who are unwilling to quit
 Motivational interviewing

Effective in meta-analysis, quit rates low
COUNSELING – Method of Delivery
 In-person * - one-on-one or group
 By telephone * - proactive quitlines
 Self-help materials – little efficacy

Newer technologies

Web- based – evidence is growing but not definitive

Text-messaging – 1 randomized trial (Lancet 2011)

Social media – little evidence
* Endorsed as effective by 2008 USPHS Guideline Update
TELEPHONE QUITLINES
 Definition
Proactive multi-session counseling by phone
 Advantages
Convenience
Privacy
 Effective
(pooled OR 1.4, 95% CI 1.3-1.6)*
 Quitlines can also provide medication
Facilitate access to medications
Strategy for promoting calls to a quitline
*Stead LF et al. Tobacco Control 2007;16(suppl 1):i3
PHARMACOTHERAPY
1st Line - 2008 US Public Health Service Guidelines
 Nicotine replacement





OR
Skin patch
Gum
Oral inhaler
1.9
Nasal spray
Lozenge
2.3
 Bupropion SR (Zyban,Wellbutrin SR)
 Varenicline (Chantix/Champix)
1.5
2.1
2.0
2.0
3.1
PLASMA NICOTINE LEVELS
Plasma nicotine level (ng/mL)
Cigarettes vs. Nicotine Replacement Products
18
16
14
Cigarette (1-2 mg)
12
Nasal spray (1 mg)
10
8
Gum (4 mg)
6
4
Patch (21 mg)
2
0
0
10 20 30 40 50 60 70 80 90 100 110 120
Time post administration (min)
NICOTINE REPLACEMENT
Long-acting, slow onset → skin patch



Constant nicotine level to avoid withdrawal
Simplest to use, best compliance
User has no control of dose
Short-acting
Intermediate onset → oral (gum, lozenge, inhaler)
More rapid onset → nasal (spray)



User controls dose
Nicotine blood levels fluctuate more
Requires more training to use properly
New Ways to Use
NICOTINE REPLACEMENT
(Supported by evidence and USPHS*)
 * Combine short- and long-acting forms
“Patch plus” regimen
 * Extend treatment to prevent relapse

Start NRT 2 weeks before quit date

Reduce to quit strategy
BUPROPION SR
(Zyban, Wellbutrin SR)

Doubles cessation rate independent of its
antidepressant effect
 Quit rates higher if add counseling
 Reduces post-cessation weight gain
 Reduces seizure threshold (risk: 1/1000)
NH
VARENICLINE
N
N
 Binds selectively to the α4β2 nicotinic receptor,
which mediates nicotine dependence
 Dual mechanism of action
 Partial agonist
Stimulates receptor to treat craving, withdrawal
 Antagonist
Prevents nicotine from binding to the receptor →
Blocks reward, reinforcement of smoking
Varenicline efficacy across studies
Continuous Abstinence Rates (Weeks 9–52)
Continuous Abstinence (%)
25
20
OR: 3.14
(95% CI: 1.93 – 5.11)
p < 0.0001
OR 4.04
(95% CI, 2.13, 7.67)
p < 0.001
OR 2.86
(95% CI,1.72, 4.11)
p < 0.001
22.4
Varenicline
Placebo
19.2
18.6
15
9.3
10
7.2
5.6
5
0
n = 355
n = 359
Stable CVD 1
1 Rigotti
et al, Circulation 2010;
2 Tashkin
n = 248
n = 251
COPD 2
n = 344
n = 341
Healthy smokers 3
D et al. Chest 2010. 3 Gonzales et al., JAMA 2006; Jorenby et al., JAMA 2006.
FDA Public Health Advisory
July 2009


“Chantix (varenicline) or Zyban (bupropion) has been
associated with reports of changes in behavior such as
hostility, agitation, depressed mood, and suicidal thoughts
or actions.”
“FDA is requiring the manufacturers of both products to
add a new Boxed Warning:
People who are taking Chantix or Zyban and experience any
serious and unusual changes in mood or behavior or who feel
like hurting themselves or someone else should stop taking the
medicine and call their healthcare professional right away.
Friends or family members …”
VARENICLINE SAFETY
The dilemma

Smokers have an increased risk of suicide.

Stopping smoking produces nicotine withdrawal
symptoms (depressed mood, anxiety, and irritability)

When these symptoms occur in a smoker who is
stopping smoking on varenicline, did the drug or did
quitting smoking cause the symptom?

Case reports cannot answer this question.

Clinical trials of varenicline detected no excess of
depression or suicidal thoughts, but these studies did
not include patients with mental illness.
VARENICLINE SAFETY
Cohort study (Gunnell et al, BMJ 2009)

UK General Practice Research Database
 Population based data: 3.6 million patients in 500 practices
 Data from electronic medical records

Patients starting smoking medication (9/06 – 5/08)
 NRT (n=63,265)
 Bupropion (n=6422)
 Varenicline (n=10,973)

Outcome: rates of suicide, suicide attempt, suicidal
thoughts, and new antidepressant therapy

Results: No evidence of increased risk of suicidal
outcomes for varenicline vs NRT, bupropion vs NRT
VARENICLINE SAFETY
My Bottom Line

Varenicline may increase risk of psychiatric symptoms in
some patients. The potential risk is not yet well defined.

Prescribing varenicline, like prescribing any drug, requires
balancing risks and benefits.
- Varenicline is one of the most effective drugs available
to treat tobacco dependence
- Continuing to smoke is clearly hazardous
 In most cases, the benefits of varenicline
outweigh the risks
Which drug is most effective?
Meta-analysis for 2008 USPHS Guideline
Drug
Nicotine patch
Other nicotine products or
bupropion
Varenicline
Estimated OR (95% CI)
1.0 (reference)
Not significantly different from
nicotine patch
1.6 (1.3-2.0)
Combinations
Long-term patch +
gum or nasal spray
Patch + bupropion SR
1.9 (1.3-2.7)
1.3 (1.0-1.8)
Varenicline vs bupropion vs placebo
CO-Confirmed 4-Wk Continuous Quit Rates - Wks 9–12
100
Response Rate (%)
60
40
OR=3.91*
OR=3.85*
(95% CI 2.74, 5.59)
(95% CI 2.69, 5.50)
OR=1.96*
OR=1.89*
(95% CI 1.42, 2.72)
(95% CI 1.37, 2.61)
44.4
44.0
30.0
29.5
20
17.7
0
N=349
N=329
17.7
N=343
N=344
Study I
Varenicline
*p<0.0001
N=340
Study II
Zyban
Placebo
Jorenby et al, Gonzales et al, JAMA, July 5, 2006
N=340
VARENICLINE vs. NICOTINE PATCH
Open label randomized controlled trial
(5 countries, n= 746)
Varenicline
NRT
60
50
56
40
43
30
20
26
20
10
0
Weeks 9-12
Weeks 9-52
End of treatment
Continuous abstinence
OR 1.70 (1.26-2.28)
OR 1.40 (0.99-1.99)
Aubin HJ. Thorax 2008
2 head-to-head randomized trials
Piper, Arch Gen Psychiat 2009; Smith, Arch Int Med 2010
 Tested 5 drug treatments (vs placebo)


Monotherapy: Patch, lozenge, bupropion
Combos: Patch + lozenge, bupropion + lozenge
 Tested drugs in 2 settings


Clinical trial (on-site counseling)
Primary care clinics (using state quitline)
 Results



Each drug was better than placebo
Combinations > monotherapy
No 1 combination was better than the other in
both trials
CYTISINE
(Tabex)
 Used for many years in Eastern Europe, Russia
 Pharmacology is similar to varenicline
 Binds selectively to the α4β2 nicotinic receptor
 Cheaper than varenicline ($6 in Russia, $15 in Poland)*
 Missing data: Is it effective (and safe)?
 New large placebo controlled trial *
 740 adult smokers in Poland
 25 days of treatment (6 pills/day → 2 pills/day)
 Validated abstinence at 1 yr : 8.4% vs 2.4% (p<.001)
 7-day abstinence at 1 yr:
13.2% vs 7.3% (p<.01)
* West et al, NEJM 2011;365:1193
PHYSICIAN INTERVENTION
 Routine advice to quit is effective
 Odds of quitting by 66% (vs no advice) *
 Brief counseling is more effective
 Odds of quitting by 37% (vs brief advice) *
 Brief intervention by other clinicians is
effective
* Cochrane reviews
5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
 ASK
all patients about smoking
 ADVISE
all smokers to quit
 ASSESS
smoker’s readiness to quit
 ASSIST
smokers to quit
 ARRANGE
follow-up care
5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
 ASK
 ADVISE
 ASSESS
 ASSIST
 ARRANGE
Core physician role
5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
 ASK
Done by office staff (‘vital sign’)
 ADVISE
Core physician role
 ASSESS
 ASSIST
 ARRANGE
5A BRIEF COUNSELING MODEL
2000 U.S. Public Health Service Guidelines
 ASK
Done by office staff
 ADVISE
Core physician role
 ASSESS
 ASSIST
 ARRANGE
Connect to office or community
supports (clinics, quit lines,…)
TOBACCO USE
BY HEALTH PROFESSIONALS
 A problem in many countries
 Health professionals act as role models
 Clinicians who smoke are less likely to counsel
patients who smoke
 Treatment strategies must include cessation
programs for health care professionals and
students
SMOKING CESSATION METHODS
2008 US Public Health Service Guidelines
 Effective treatments

Counseling

Pharmacotherapy

Combination - better than either one alone
 More is better but brief intervention works
 Treating tobacco is highly cost-effective
FCTC Article 14 - Implementation
World Health Organization
Countries should offer 3 types of treatment
 Advice to quit in primary health care
 Telephone quit lines – free and accessible
 Pharmacotherapies – low-cost and accessible
Thank You