nancy rigotti, md
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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 - PowerPoint PPT PresentationTRANSCRIPT
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
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 ReportWorld 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?
Irritability, anger, impatience Restlessness Difficulty concentrating Insomnia Anxiety Depressed mood Increased appetite
Pharmacologic nicotine dependence → Craving (nicotine “hunger”)
→ Nicotine withdrawal symptoms
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 low-income countries
Less awareness of health risks Fewer have tried to quit and failed
Biology is relatively constant
Cultural context varies by country
SMOKING CESSATION METHODS2008 US Public Health Service Guidelines
Effective treatments
More is better but brief intervention works
Treating tobacco is highly cost-effective
Counseling
Pharmacotherapy
Combination - better than either one alone
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
AdvantagesConveniencePrivacy
Effective (pooled OR 1.4, 95% CI 1.3-1.6)*
Quitlines can also provide medicationFacilitate access to medicationsStrategy for promoting calls to a
quitline
*Stead LF et al. Tobacco Control 2007;16(suppl 1):i3
PHARMACOTHERAPY1st Line - 2008 US Public Health Service Guidelines
Nicotine replacement OR Skin patch 1.9
Gum 1.5
Oral inhaler 2.1
Nasal spray 2.3
Lozenge 2.0
Bupropion SR (Zyban,Wellbutrin SR) 2.0
Varenicline (Chantix/Champix) 3.1
0
2
4
6
8
10
12
14
16
18
0 10 20 30 40 50 60 70 80 90 100 110 120
Time post administration (min)
Pla
sma
nico
tine
leve
l (ng
/mL)
Cigarette (1-2 mg)
Nasal spray (1 mg)
Gum (4 mg)
Patch (21 mg)
PLASMA NICOTINE LEVELSCigarettes vs. Nicotine Replacement Products
NICOTINE REPLACEMENT
Long-acting, slow onset → skin patch
Short-acting Intermediate onset → oral (gum, lozenge, inhaler)
More rapid onset → nasal (spray)
Constant nicotine level to avoid withdrawal Simplest to use, best compliance User has no control of dose
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
Reduces post-cessation weight gain
Quit rates higher if add counseling
Reduces seizure threshold (risk: 1/1000)
VARENICLINE
Binds selectively to the α4β2 nicotinic receptor, which mediates nicotine dependence
Dual mechanism of action
Partial agonist Stimulates receptor to treat craving, withdrawal
AntagonistPrevents nicotine from binding to the receptor →Blocks reward, reinforcement of smoking
NH
N
N
OR 2.86(95% CI,1.72, 4.11)
p < 0.001
25
20
15
10
0
Con
tinuo
us A
bstin
ence
(%
)
n = 355 n = 359
19.2
7.2
OR: 3.14(95% CI: 1.93 – 5.11)
p < 0.0001
18.6
5.6
OR 4.04(95% CI, 2.13, 7.67)
p < 0.00122.4
9.3
Stable CVD 1
n = 344 n = 341
Healthy smokers 3
n = 248 n = 251
COPD 2
Varenicline
Placebo
5
Varenicline efficacy across studiesContinuous Abstinence Rates (Weeks 9–52)
1 Rigotti et al, Circulation 2010; 2 Tashkin D et al. Chest 2010. 3 Gonzales et al., JAMA 2006; Jorenby et al., JAMA 2006.
FDA Public Health AdvisoryJuly 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 SAFETYThe 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 SAFETYCohort 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 SAFETYMy 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?Which drug is most effective?Meta-analysis for 2008 USPHS GuidelineMeta-analysis for 2008 USPHS Guideline
DrugDrug Estimated OR Estimated OR (95% CI)(95% CI)
Nicotine patchNicotine patch 1.0 (reference)1.0 (reference)Other nicotine products or Other nicotine products or bupropionbupropion
Not significantly different from Not significantly different from nicotine patchnicotine patch
VareniclineVarenicline 1.6 (1.3-2.0)1.6 (1.3-2.0)
CombinationsCombinations
Long-term patch + Long-term patch +
gum or nasal spraygum or nasal spray1.9 (1.3-2.7)1.9 (1.3-2.7)
Patch + bupropionPatch + bupropion SRSR 1.3 (1.0-1.8)1.3 (1.0-1.8)
Varenicline vs bupropion vs placeboCO-Confirmed 4-Wk Continuous Quit Rates - Wks 9–12
OR=3.91OR=3.91**
(95% CI 2.74, 5.59)
OR=1.96OR=1.96**
(95% CI 1.42, 2.72)
OR=3.85OR=3.85**
(95% CI 2.69, 5.50)
OR=1.89OR=1.89**
(95% CI 1.37, 2.61)
100
44.4 44.0
30.029.5
17.717.7
0
20
40
60
Study I Study II
Res
po
nse
Rat
e (%
)
Varenicline Zyban Placebo
N=349 N=329 N=344 N=343 N=340 N=340
*p<0.0001 Jorenby et al, Gonzales et al, JAMA, July 5, 2006
VARENICLINE vs. NICOTINE PATCHOpen label randomized controlled trial
(5 countries, n= 746)
0
10
20
30
40
50
60
Weeks 9-12 Weeks 9-52
Varenicline NRT
Aubin HJ. Thorax 2008
End of treatmentOR 1.70 (1.26-2.28)
Continuous abstinenceOR 1.40 (0.99-1.99)
2620
56
43
2 head-to-head randomized trialsPiper, 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 MODEL2000 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 MODEL2000 U.S. Public Health Service Guidelines
ASK
ADVISE Core physician role
ASSESS
ASSIST
ARRANGE
5A BRIEF COUNSELING MODEL2000 U.S. Public Health Service Guidelines
ASK Done by office staff (‘vital sign’)
ADVISE Core physician role
ASSESS
ASSIST
ARRANGE
5A BRIEF COUNSELING MODEL2000 U.S. Public Health Service Guidelines
ASK Done by office staff
ADVISE Core physician role
ASSESS
ASSIST Connect to office or
community
ARRANGE supports (clinics, quit lines,
…)
TOBACCO USE TOBACCO USE BY HEALTH PROFESSIONALSBY HEALTH PROFESSIONALS
A problem in many countriesA problem in many countries
Health professionals act as role modelsHealth professionals act as role models
Clinicians who smoke are less likely to counsel Clinicians who smoke are less likely to counsel patients who smokepatients who smoke
Treatment strategies must include cessation Treatment strategies must include cessation programs for health care professionals and programs for health care professionals and studentsstudents
SMOKING CESSATION METHODS2008 US Public Health Service Guidelines
Effective treatments
More is better but brief intervention works
Treating tobacco is highly cost-effective
Counseling
Pharmacotherapy
Combination - better than either one alone
FCTC Article 14 - ImplementationWorld 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