Treatment of Tobacco Dependence in 2012 J. Taylor Hays, MD Professor of Medicine

Treatment of Tobacco
Dependence in 2012
J. Taylor Hays, MD
Professor of Medicine
Associate Director
Nicotine Dependence Center
Mayo Clinic
Rochester, MN
Disclosures
•
•
Relevant Financial Relationship(s)
– Grant/Research Support – Pfizer
– Grant/Research Support- Nabi Biopharmaceuticals
Off Label Usage
– Nicotine replacement therapy; Manufacturer - various
Learning Objectives
Participants will be able to:
• Choose appropriate pharmacotherapy for a smoker motivated to quit
• Identify the optimal length of pharmacological treatment for smokers
• Describe brief behavioral treatment for tobacco dependence
2
17.3%
Behavioral Risk Factor Surveillance System
Centers for Disease Control and Prevention
3
Case #1
• 55 yo man with CAD; asymptomatic after
successful stent placement 6 months ago
• Smokes 25+ cigarettes per day and smokes his
first one within 5 minutes of waking
• He quit smoking for 2 weeks by trying a 14 mg
nicotine patch after his stent, but “was a bear to
live with” until he relapsed
• He is here for a follow-up with you, and when
asked tells you he is willing to try quitting again
4
Case # 1
Which of the following recommendations will result in the
best tobacco abstinence outcome 6 months from now?
1.
2.
3.
4.
5.
Nicotine patch 21 mg per day for 8 weeks
Nicotine gum 2 mg as needed for 12 weeks
Nicotine lozenge 4 mg as needed for 4 weeks
Nicotine patch 21 mg per day plus nicotine
lozenge 2 mg as needed for 12 weeks
Bupropion SR 150 mg twice daily for 7 weeks
5
Case # 1
Which of the following recommendations will result in the
best tobacco abstinence outcome 6 months from now?
1.
2.
3.
4.
5.
Nicotine patch 21 mg per day for 8 weeks
Nicotine gum 2 mg as needed for 12 weeks
Nicotine lozenge 4 mg as needed for 4 weeks
Nicotine patch 21 mg per day plus nicotine
lozenge 2 mg as needed for 12 weeks
Bupropion SR 150 mg twice daily for 7 weeks
6
USPHS Guideline
• Identify every tobacco user
• Provide advice to quit and practical
counseling no matter how brief
(behavioral therapy)
• Motivate health behavior change (MI)
• Combine brief behavioral treatment with
effective pharmacotherapy for everyone
making a quit attempt
– Exceptions include contraindications and special
populations where evidence is poor
7
USPHS Clinical Practice Guideline- 2008
The 5 A’s
•
•
•
•
•
ASK about tobacco use
ADVISE to stop
ASSESS willingness to make an attempt
ASSIST in the stop attempt
ARRANGE for a follow-up visit
•
•
•
•
•
S- Smoking status
M- Motivational message
A- and
R- Refer for
T- Treatment
8
www.ahrq.gov
Effect of Contact Intensity
Cessation by intensity of person-to-person contact
Contact*
None
Minimal
Brief
Counseling
O.R.
1.0
1.3
1.6
2.3
Cessation%
10.9
13.4
16.0
22.1
*minimal<3mins; brief >3 to <10mins; counseling > 10mins.
Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008
Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and
Human Services. Public Health Service. May 2008.
9
Motivational Interviewing
• Method of enhancing motivation for health
behavior change
• Brief intervention for patients not ready to
make a quit attempt
• Spirit of MI:
–
–
–
–
Express empathy
Develop discrepancy
Roll with resistance
Support self-efficacy
10
Motivational Interviewing
It’s a dance…
…not a wrestling match!
Baron von Raschke
11
Effectiveness and Abstinence Rates for Medications Compared
With Placebo or Standard-Dose Nicotine Patch at 6-Months
Medication
Arms
Estimated abstinence
rate (95% CI)
Estimated OR vs
Placebo (95% CI)
Estimated OR vs
Nicotine patch*
(95% CI)
Monotherapies
Varenicline (2 mg/d)
5
33.2 (28.9-37.8)
3.1 (2.5-3.8)
1.6 (1.3-2.0)
Nicotine nasal spray
4
26.7 (21.5-32.7)
2.3 (1.7-3.0)
1.2 (0.9-1.6)
High-dose nicotine patch (>25 mg) (includes
both standard or long-term duration)
4
26.5 (21.3-32.5)
2.3 (1.7-3.0)
1.2 (0.9-1.6)
Long-term nicotine gum (>14 weeks)
6
26.1 (19.7-33.6)
2.2 (1.5-3.2)
1.2 (0.8-1.7)
Varenicline (1 mg/d)
3
25.4 (19.6-32.2)
2.1 (1.5-3.0)
1.1 (0.8-1.6)
Nicotine inhaler
6
24.8 (19.1-31.6)
2.1 (1.5-2.9)
1.1 (0.8-1.5)
Bupropion SR
26
24.2 (22.2-26.4)
2.0 (1.8-2.2)
1.0 (0.9-1.2)
Nicotine patch (6-14 weeks)
32
23.4 (21.3-25.8)
1.9 (1.7-2.2)
1.0
Long-term nicotine patch (>14 weeks)
10
23.7 (21.0-26.6)
1.9 (1.7-2.3)
1.0 (0.9-1.2)
Nortriptyline
5
22.5 (16.8-29.4)
1.8 (1.3-2.6)
0.9 (0.6-1.4)
Nicotine gum (6-14 weeks)
15
19.0 (16.5-21.9)
1.5 (1.2-1.7)
0.8 (0.6-1.0)
*Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Clinical
Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services. Public Health
Service. May 2008.
12
Effectiveness and Abstinence Rates for Medication Combinations
Compared With Placebo or Standard-Dose Nicotine Patch at 6-Months
Medication
Arms
Estimated abstinence
rate (95% CI)
Estimated OR vs
Placebo (95% CI)
Estimated OR vs
Nicotine patch* (95%
CI)
Combination Therapies
Patch (long-term; >14 weeks) + ad lib NRT
(gum or spray)
3
36.5 (28.6-45.3)
3.6 (2.5-5.2)
1.9 (1.3-2.7)
Patch + bupropion SR
3
28.9 (23.5-35.1)
2.5 (1.9-3.4)
1.3 (1.0-1.8)
Patch + nortriptyline
2
27.3 (17.2-40.4)
2.3 (1.3-4.2)
0.9 (0.6-1.4)
Patch + inhaler
2
25.8 (17.4-36.5)
2.2 (1.3-3.6)
1.1 (0.7-1.9)
*Fiore MC, Jaén CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008
Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and
Human Services. Public Health Service. May 2008.
13
Combination Pharmacotherapy
• Sustained release NRT (patch) +
Immediate release NRT
– Provides steady nicotine level
– Allows patient to respond to urges
• Medications with different targets
– NRT + Bupropion SR
– Varenicline + Bupropion SR?
• Monotherapy with immediate release
NRT should be used rarely
14
COMBINATION THERAPY
•RCT of 1504 smokers in a
research clinic
•Received 1 of 6 treatments
for 8 weeks
•6 brief counseling sessions
•7-day point prevalence
abstinence at 8 wks and 6
months
Piper M, et al. Arch Gen Psychiat
2009;66:1253-62.
15
COMBINATION THERAPY
•RCT of 1346 smokers recruited from 12 primary
care clinics in Wisconsin
•Received 1 of 5 active treatments for 8 weeks
•Referred for counseling via telephone “quitline”
•7-day point prevalence at 8 wks and 6 months
Smith SS, et al. Arch Intern Med 2009;169:2148-55
16
TRIPLE COMBINATION THERAPY
Steinberg MB, et al. Annals Intern Med 2009; 150:447-454.
•RCT of 127 smokers with known
CVD, COPD, cancer, diabetes
•Compared triple combination
(nicotine patch + bupropion + nicotine
inhaler) to patch alone
•Triple therapy mean treatment
duration 89 days
•Patch alone mean treatment duration
35 days
•At 6 months 7 day point prevalence
abstinence:
•Triple therapy 35%
•Patch 19%
•(OR 2.57, 95% CI 1.05 to 6.32,
p-value 0.04)
17
USPHS Clinical Practice Guideline- 2008
Long-term Medication Use
• Smokers who report persistent withdrawal symptoms.
• Smokers who have had relapse after stopping
medication.
• Smokers at higher risk for relapse
– More dependent (>20 CPD; smokes w/in 30 minutes of waking)
– Other smokers in household
– Psychiatric comorbidity (includes substance abuse hx)
• Smokers who desire long-term therapy.
• Use does not present a known health risk.
18
How Long to Treat with NRT?
• Most patients want to stop NRT too soon
• We cannot predict who will have better
outcomes with longer treatment
• Nicotine patch therapy for 6 months outperforms
a standard 8 week treatment course
• Cost per additional quitter was $2482 (95% CI,
$1519 to $6781)
19
Adherence to NRT Treatment
Balmford J, et al. Nicotine & Tobacco Research 2011;13:94-102
•Only 28.6% of NRT users completed the recommended 8 weeks of
treatment
•Most quit prematurely because they believed the medication was not
working, had unwanted side effects or believed that they no longer
needed treatment.
20
Nicotine patch 8 vs 24 weeks: RCT of 568 smokers
Schnoll R A et al. Ann Intern Med 2010;152:144-151
©2010 by American College of Physicians
21
Bupropion SR Prolonged Treatment
Hays JT, et al. Annals Intern Med 2001;135:423-433.
90
80
70
60
%
50
Abstinent 40
30
20
10
0
PBO
BUP-SR
12
wks
24
wks
52
wks
N= 461 smokers
Abstinent after 8 weeks of open label bupropion SR treatment
Randomized to placebo or bupropion for additional 44 weeks (total 52 weeks of treatment)
Bupropion compared with placebo at 12, 24 and 52 weeks p-value < 0.05
22
Varenicline Maintenance of Abstinence
Study
Response Rate (%)
100
Wks 13–24
OR=2.47
80
60
Wks 13–52
p<0.0001
70.6
70.6
OR= 1.35
p=0.0126
49.8
40
44.0
37.1
20
0
N=602
Varenicline
N=604
Placebo
N=602
Varenicline
N=604
Placebo
Tonstad et al. JAMA 2006;296:64-71
23
Higher Dose Nicotine Patch
• There is a dose-response effect
• Long-term abstinence improved;
RR of 1.15 (95% CI: 1.01 to 1.30)*
• Treatment-related AE’s are
uncommon
• Withdrawal symptoms less with
higher dose NRT
*Cochrane Database of Systematic Reviews 2008
24
Nicotine Patch Dose
Based on Cotinine and CPD
Cotinine
<200 ng/ml
Cigs per day
< 15
Patch dose
14-21 mg/d
200-300 ng/ml
16-40
21-35 mg/d
>300 ng/ml
> 40
35-42+ mg/d
25
Patch Dosing Schedule
• Use initial dose for 4-6 weeks
• Taper 7-14mg steps every 2-6
wks
• Length of therapy varies based
on patient response
• Withdrawal symptoms while
tapering are mild to nonexistent
• Advise using overnight
26
Take Home #1
• Brief behavioral treatment is effective for treating
tobacco dependence
• Pharmacotherapy is effective for treating tobacco
dependence (NRT, bupropion, varenicline)
• Behavioral treatment and pharmacotherapy together are
best
• Combination pharmacotherapy results in superior
abstinence compared with single agent therapy for many
smokers
• Use combinations in smokers who have tried and
relapsed with monotherapy AND in smokers with
important comorbidity
27
Take Home #2
• Use pharmacotherapy for at least 12 weeks in
everyone
• Consider higher doses of NRT for heavier
smokers
• Treat those at risk for relapse for 6+ months
– persistent strong urges to smoke
– higher dependence
– comorbid medical/psychiatric illness
– past substance abuse
– unable to quit on target date
28