Upload
renee-wood
View
14
Download
0
Tags:
Embed Size (px)
DESCRIPTION
New Pharmacotherapies for Assisting Smokers in Their Cessation Efforts- Update. Frank Vocci, Ph.D. Director, DPMCDA June 7, 2006. Rimonabant. CB1 inverse agonist/ antagonist Stratus-US Study ( unpublished) Quit rates in the 20 mg group were double that of placebo - PowerPoint PPT Presentation
Citation preview
New Pharmacotherapies for Assisting Smokers in Their Cessation Efforts-
Update
Frank Vocci, Ph.D.Director, DPMCDA
June 7, 2006
Rimonabant
• CB1 inverse agonist/ antagonist• Stratus-US Study ( unpublished)• Quit rates in the 20 mg group were
double that of placebo• Weight gain in the 20 mg group was 0.4
kg for 12 weeks versus 3.6 kg for placebo
• FDA sent Sanofi a “non-approvable” letter… contents unknown
Rimonabant
• May be sought after by smokers who want to quit but don’t want to gain weight
• Could be tested with other therapies, especially NRT for additive effects
• Has other metabolic effects which can independently reduce cardiovascular disease risk
Nicotine Vaccine
• Being produced by three companies
• Potential indications:– Aid to cessation– Prevention of relapse– And prevention of smoking
Nicotine Vaccine
Nicotine Vaccine
Nicotine Vaccine Blocks Nicotine Self-
Administration
NicVAX
Hedonic Value and the Possible Role of a Vaccine
Nicotine Vaccine Update
• Nabi trial will be complete in September 2007
And now for the question: Can Someone Smoke Enough to Overcome the Vaccine
Titer ?
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003.
AgeAge
Age at tobacco, at alcohol and at cannabis dependence, as per DSM IV
0.00.0
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
1.21.2
1.41.4
1.61.6
1.81.8
55 1010 1515 2020 2525 3030 3535 4040 4545 5050 5555 65656060
% in
eac
h a
ge
gro
up
to
dev
elo
p
% in
eac
h a
ge
gro
up
to
dev
elo
p
firs
t-ti
me
dep
end
ence
firs
t-ti
me
dep
end
ence
THCTHCALCOHOLALCOHOL
TOBACCOTOBACCO
Addiction Is a Developmental Disease starts in adolescence and childhood
Addiction Is a Developmental Disease starts in adolescence and childhood
7575
Source: Adriana, W. et al., J of Neurosci, 23(11), pp. 4712-4716, June 1, 2003.Source: Adriana, W. et al., J of Neurosci, 23(11), pp. 4712-4716, June 1, 2003.
During A Between Session Progressive Ratio Schedule for
Nicotine Self Administration
During A Between Session Progressive Ratio Schedule for
Nicotine Self Administration
Animals Pre-Exposed to Nicotine During Peri- and Post-Adolescence Differed
Animals Pre-Exposed to Nicotine During Peri- and Post-Adolescence Differed
For Transcript Levels of DifferentSubunits of the nAChRs in
the Ventral Midbrain
For Transcript Levels of DifferentSubunits of the nAChRs in
the Ventral Midbrain
When reading emotion, teens (left) rely more on the amygdala, while adults (right) rely more on the frontal cortex.
Deborah Yurgelon-Todd, 2000
Emotions
Using Brain Imaging TechnologyUsing Brain Imaging Technology
• fMRI used to determine Coke vs. Pepsi preference • fMRI used to determine Coke vs. Pepsi preference
…to better communicate with adolescents…to better communicate with adolescents
McClure et al., 2004McClure et al., 2004
Branding Bias & Neural Activation
Using Brain Imaging TechnologyUsing Brain Imaging Technology
• fMRI used to determine preference for Super Bowl commercials
• fMRI used to determine preference for Super Bowl commercials
…to better communicate with adolescents…to better communicate with adolescents
Iacoboni et al., 2006
Iacoboni et al., 2006
NFL Disney AdNFL Disney Ad
FedEx Caveman AdFedEx Caveman Ad
Super Bowl Ad- Activity in R IFG- Empathy
Brain Activation and Acceptance or Rejection of
an Offer
Immediate versus Delayed Reward Systems- Sanfey et
al 2006
Summary
• Brain imaging can detect whether an intended effect is being produced
• The effect may contradict what the individual actually verbalizes… people thought the FedEx ad was funny but the brain image showed a fear response
• Multiple systems (Immediate reward, empathy, delayed reward, memory/bias, negative emotions) are involved in producing a response and emotional versus cognitive conflict resolution may ensue
• Brain imaging could be used to determine whether an ad intended to increase consumer demand hit the mark or had the opposite effect
• It may provide a more accurate, scientifically based assessment of consumer choice and decision-making
Varenicline• Partial agonist at the 4ß2 nicotine
receptor• Partial agonists have some effects like
nicotine but can also act like antagonists
• A dual mechanism of action is proposed:– Partial nicotine-like effects– Nicotine blockade from cigarette smoking
Varenicline
Varenicline Phase II Trials- Tonstad study
Drug 12 WeekQuit Rate %
52 WeekQuit Rate %
placebo 18 10
Bupropion 30 16
Varenicline 44 22
New Therapies
• Offer new prospects for smokers looking for an assist to quit smoking
• Each may have distinct advantages• The vaccine may be useful for relapse
prevention• Other medications are also being
developed