Pharmacotherapy for Youth Smoking Cessation

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Pharmacotherapy for Youth Smoking Cessation

• The 2009 Virginia Forum
• on Youth Tobacco Use
• April 14, 2009

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Goals of the Presentation

• What do we know about the effects of
  pharmacotherapy on adolescent smoking?
• quitting
• smoking rate, craving, withdrawal
• safety
• adherence
• What do we need to know more about?

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Context

• PHS Clinical Guidelines
• Insufficient evidence
• 7 studies over last 13 years
• Adult Quitting Benchmarks
• Pharmacotherapy ? 2x to 3x quit rates
• Adolescent Quitting Benchmarks
• Sussman review (2002) psychosocial txs
• Experimental tx quit rate 12
• Control tx quit rate 7

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Monitoring the Future 2008National Smoking
Prevalence
N15,100
N14,000
N15,700
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Published Pharmacotherapy Trials for Adolescent
Smoking Cessation

• Nicotine patch
• Smith et al. (1996) open label
• Hurt et al. (2000) open label
• Hanson et al. (2003) randomized
• Nicotine patch and gum
• Moolchan et al. (2005) randomized
• Bupropion (i.e., Wellbutrin, Zyban)
• Upadhyaya et al. (2004) open label
• Muramoto et al. (2008) randomized
• Bupropion plus nicotine patch
• Killen et al. (2004) randomized

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Nicotine Patch Therapy Non-randomized Open-label
Trials
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Study 1 Smith et al. (1996)Nicotine Patch
Open-Label Trial

• TREATMENT
• 8 weeks
• 22 mg/day (6 wk)
• 11 mg/day (2 wk)
• Plus
• weekly individual behavioral counseling group
  support (8 wk)

• SAMPLE
• 22 daily smokers
• 68 females
• Ages 13 to 17
• 20 cpd

Smith TA, House RF, Croghan IT, Gauvin TR,
Colligan RC, Offord KP, Gomez-Dahl LC, Hurt RD.
Nicotine patch therapy in adolescent smokers.
Pediatrics. 199698(4)659-667
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Study 1 Smith et al. (1996)
Verified Abstinence (CO lt 8 ppm)
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Study 2 Hurt et al. (2000)Nicotine Patch
Open-Label Trial

• SAMPLE
• 101 daily smokers
• 41 females
• Ages 13 to 17
• 10 cpd (M20)

• TREATMENT
• 6 weeks
• 15 mg/16 hour
• Plus
• 10-15 min. counseling at pts request

Hurt RD, Croghan GA, Beede SD, Wolter TD, Croghan
IT, Patten CA. Nicotine patch therapy in 101
adolescent smokers. Arch Pediatr Adolesc Med.
2000154(1)31-37.
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Study 2 Hurt et al. (2000)
Verified Abstinence (CO lt 8 ppm)
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Nicotine Replacement Therapy Randomized Trials
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Study 1 Hanson et al. (2003)Nicotine Patch vs.
Placebo

• TREATMENT
• 10 weeks
• 14-21 mg/day (6 wk)
• 7-14 mg/day (4 wk)
• Tapered dose, dep on cpd
• vs. Placebo
• Plus
• 10-15 min counseling weekly
• Contingency management
• for COs lt 8 ppm

• SAMPLE
• 100 daily smokers
• 57 females
• Ages 13 to 19
• 10 cpd

Hanson K, Allen S, Jensen S, Hatsukami D.
Treatment of adolescent smokers with the nicotine
patch. Nicotine Tob Res. 20035(4)515-526.
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Study 1 Hanson et al. (2003)
ns
26 contacted Data NR
20 contacted Data NR
Verified Abstinence (CO lt 5 ppm)
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Study 2 Moolchan et al. (2005)Patch vs. Gum vs.
Placebo

• SAMPLE
• 120 daily smokers
• 70 females
• Ages 13 to 17
• 10 cpd
• 5 FTND
• 75 had 1 psych dx

• TREATMENT
• 12 weeks
• vs. Placebo Patch Gum
• Plus
• Group CBT weekly

Nicotine Patch 21 mg/day
Nicotine Gum 24 cpd 2 mg/day lt24 cpd 4
mg/day
Moolchan ET, Robinson ML, Ernst M, Cadet JL,
Pickworth WB, Heishman SJ, Schroeder JR. Safety
and efficacy of the nicotine patch and gum for
the treatment of adolescent tobacco addiction.
Pediatrics. 2005 115(4)e407-e414.
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Study 2 Moolchan et al. (2005)
Patch gt Placebo (p.058)
Verified Abstinence (CO lt 6 ppm)
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Most Common Side EffectsThree NRT Trials (Smith,
Hurt, Hanson)
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Side Effects NRT vs. Placebo
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Summary of NRT Trials

• NRT safe and well-tolerated
• Two Open Label Trials
• Very low quit rates ( 5)
• Two randomized trials
• 1 High end-of-tx quit rates
• No effect of nicotine patch
• 2 High end-of-tx quit rate in patch group
• Patch gt placebo
• Abstinence maintained thru 6M
• No effect of nicotine gum

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Bupropion Open Label trial
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Upadhyaya et al. (2004)Bupropion Open Label Trial

• SAMPLE
• 16 daily smokers
• 11 with ADHD dx
• 37.5 females
• Ages 12 to 19 (M18)
• 5 cpd (M20)

• TREATMENT
• 6 weeks
• 300 mg
• (2 150 mg pills/day)
• Plus
• 2 30-min counseling sessions
• Weekly outpatient visits

Upadhyaya HP, Brady KT, Wang W. Bupropion SR in
adolescents with comorbid ADHD and nicotine
dependence A pilot study. J Am Acad Child
Adolesc Psychiatry. 200443(2)199-205.
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Upadhyaya et al. (2004)
6 wk
4 wk
Abstinence via self-report
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Bupropion Randomized Trial
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Muramoto et al. (2007)Bupropion (150 mg, 300 mg)
vs. Placebo

• SAMPLE
• 312 daily smokers
• 46 females
• Ages 14 to 17
• 6 cpd
• CO 10 ppm
• 2 prior quit attempts
• No current psych dxs

• TREATMENT
• 6 weeks
• vs. Placebo
• Plus
• Brief counseling

Bupropion SR 150 mg/day
Bupropion SR 300 mg/day
Muramoto ML, Leischow SJ, Sherrill D, Matthews E,
Strayer LJ. A randomized, double-blind,
placebo-controlled trial of two doses of
sustained release bupropion for adolescent
smoking cessation. Arch Pediatr Adolesc Med. 2007.
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Muramoto et al. (2007)
Bup 300 gt Plac (p.03)
p.049 overall
Verified Abstinence (CO lt 10 ppm or cotinine lt
50 mg/L)
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Side Effects BupropionMuramoto study



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Bupropion Nicotine Patch Randomized Trial
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Killen et al. (2004)Bupropion Patch vs.
Placebo Patch

• SAMPLE
• 211 daily smokers
• 31 females
• Ages 15 to 18
• 10 cpd
• 1 prior quit attempts
• 10 on SDI dependence
• Current MDD excluded

• TREATMENT
• 10 weeks
• Plus
• Nicotine Patch
• dose dep. on cpd
• Weekly group skills training

Bupropion SR 150 mg/day
Placebo
Killen JD, Robinson TN, Ammerman S, Hayward C,
Rogers J, Stone C, Samuels D, Levin SK, Green S,
Schatzberg AF. Randomized clinical trial of the
efficacy of bupropion combined with nicotine
patch in the treatment of adolescent smokers. J
Consult Clin Psychol. 200472729-735.
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Killen et al. (2004)
ns
ns
Verified Abstinence (CO lt 9 ppm or cotinine lt 20
mg/L)
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Summary of Bupropion Trials

• Bup safe and generally well-tolerated
• One Open Label Trial
• High end-of-tx quit rate with 300 mg
• Low completion rate
• Two Randomized Trials
• 1 Modest end-of-tx quit rate
• 300 mg gt placebo
• 300 mg quit rate maintained at 6M
• No effect of 150 mg
• 2 High end-of-tx quit rates
• No effect of 150 mg

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NRT BupropionOther Effects
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Summary

• Insufficient evidence
• NRT
• Nicotine patch gt placebo
• quit rate, craving, and WD sxs
• No effect of gum
• But compliance with gum was poor
• BUP
• 300 mg gt placebo
• Short-term quit rate
• No effect of 150 mg
• But med compliance predicted quitting

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What do we need to know more about?
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What Explains Poorer Outcomes in Adolescents?

• Shorter intervention periods
• Lower dose received
• Low completion rates
• Low adherence rates
• Interventions to boost adherence?
• Tests of mechanisms (lab and clinical trials)
• Does med reduce wd/craving?
• Does decreased wd/craving reduce relapse?
• Other pharmacotherapies
• Other psychosocial tx combinations