Wausau May

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Transcript Wausau May

Varenicline: A Tale of
Three Molecules
Douglas E. Jorenby, Ph.D.
Associate Professor of Medicine
Univ. of WI School of Medicine and Public Health
The Center for Tobacco Research and Intervention
The University of Wisconsin School of Medicine and Public Health
Disclosures
Research support from NIDA
(P50DA019706-09) , Pfizer,
Nabi Biopharmaceuticals
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Tobacco results in a true drug
dependence
• Tobacco dependence exhibits classic
characteristics of drug dependence
• Nicotine:
– Is Psychoactive
– Produces Tolerance
– Causes physical dependence
characterized by withdrawal
symptoms upon cessation
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Is It All About Withdrawal?
• Kenford et al. (2002) analysis of
505 smokers from three nicotine
patch studies:
“Indeed, it appears that the extent
that withdrawal symptomatology
predicts relapse is largely due to
the ability of withdrawal measures
to tap affect…”
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Stewart, de Wit & Eikelboom. Psych Review, 1984.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
This is your brain on dopamine
Tapper et al. Science, 2004.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Varenicline
• Small, water soluble molecule
• 92% excreted unchanged in
urine
• 24 hr. half-life
• No competition for P450
pathway
Obach et al. Drug Metab Dispos., 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Comparative Evidence Base
• Bupropion SR 2 RCTs with
1,508 participants
• Varenicline 5 RCTs with 5,265
participants
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Dose Level & Titration
• Placebo-controlled, doubleblind RCT
• N=647
• 0.5 mg BID vs. 1.0 mg BID
• Titrated vs. Non-titrated
• Weekly individual counseling
Oncken et al. Arch Intern Med, 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Point Prevalence Outcome
Oncken et al. Arch Intern Med, 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Oncken et al. Arch Intern Med, 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Comparative Efficacy
• Placebo-controlled, doubleblind RCT
• N=1027 (+1025)
• 1.0 mg BID vs. 150 mg BID
bupropion SR
• Weekly individual counseling
Jorenby et al., JAMA. 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Point Prevalence Outcome
Jorenby et al., JAMA. 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Modified Cigarette Evaluation
Questionnaire Subscales
Varenicline
p-value vs.
Placebo
Smoking Satisfaction
<.001
Psychological Reward
<.001
Respiratory Tract Sensations
.01
Craving Reduction
.04
Aversion
n.s.
Bupropion SR
Smoking Satisfaction
Psychological Reward
<.001
<.001
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Extended Treatment
• Open-label treatment for 12
weeks
• Then randomized, double-blind
assignment to 12 additional
weeks of varenicline or placebo
• N=1210
• Weekly individual counseling
Tonstad et al. JAMA, 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Point Prevalence Outcome
Tonstad et al. JAMA, 2006.
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health
Looking to the future
• Withdrawal relief may be just a
first step
• More than one way to alter
rewarding properties of smoking?
• Extending both treatment and the
population?
• Matching treatments to patients
The Center for Tobacco Research and Intervention
University of Wisconsin School of Medicine and Public Health