Post on 03-Jan-2016
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Smoking Cessation:Smoking Cessation:What works and why… What works and why…
A Medical ModelA Medical Model
Stephen I RennardUniversity of Nebraska
Florianopolis, BrazilOctober 2009
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EFFECT OF PRICE ON TEEN SMOKING IN CANADA
EFFECT OF PRICE ON TEEN SMOKING IN CANADA
Sweanor et al. Non-smoker's Rights Assn. 1993Sweanor et al. Non-smoker's Rights Assn. 1993
9595909085858080757500
100100
200200
300300
1010
2020
3030
4040
Calendar YearCalendar Year
Price (Canada $)Price (Canada $) % smokers (15-19)% smokers (15-19)
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Student Smoking Behavior in the Student Smoking Behavior in the United States (1991-2004)United States (1991-2004)
Johnston et al. U. Michigan www.monitoringthefuture.org
Students ever using cigarettes (%)Students ever using cigarettes (%)
2020
3030
4040
5050
6060
7070
19901990 19951995 20002000 20052005
YearYear
12th Grade12th Grade
10th Grade10th Grade
8th Grade8th Grade
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NICOTINE WITHDRAWAL SYMPTOMSNICOTINE WITHDRAWAL SYMPTOMS
• Craving to smokeCraving to smoke• IrritabilityIrritability• Awakening from sleepAwakening from sleep• BradycardiaBradycardia• AnxietyAnxiety• Impaired concentrationImpaired concentration• Inpaired reaction timeInpaired reaction time
• RestlessnessRestlessness• DrowsinessDrowsiness• ImpotenceImpotence• ConfusionConfusion• HungerHunger• Weight gainWeight gain• DepressionDepression
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Nicotine
Increased ReceptorsIncreased Occupancy
Withdrawal
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Cues
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Cues
Conditioned Response
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Nicotine
Cues
Conditioned Response
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Nicotine
Increased ReceptorsIncreased Occupancy
Withdrawal
Cues
Conditioned Response
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Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning
Nicotine
Increased ReceptorsIncreased Occupancy
Withdrawal
Cues
Conditioned Response
Persistent Smoking
Nicotine Levels in a SmokerNicotine Levels in a Smoker
High
Withdrawal
Time
Nic
oti
ne
Le
vel
15
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Nicotine formulations: Efficacy
Placebo
Odds Ratio
Patch0
1
2
3
4
Gum Inhaler NasalSpray
Lozenge(2mg)
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat2.chapter.28163f
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Nicotine Levels in a SmokerNicotine Levels in a Smoker
High
Withdrawal
Time
Nic
oti
ne
Le
vel
Dose, exposureDose, exposure
Eff
ect
Eff
ect
0%0%
100%100%Maximum effectMaximum effect
50%50%
Rationale – Partial AgonistRationale – Partial Agonist
Full agonistFull agonist
Craving; Craving; Withdrawal Withdrawal reliefrelief
Blocks Blocks rewardreward
Partial agonistPartial agonist
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Effect of Varenicline on Craving and Effect of Varenicline on Craving and RewardReward
Gonzales et al. JAMA 296: 47, 2006
ScoreScore
SatisfactionSatisfaction RewardReward EnjoymentEnjoyment CravingCraving11
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33
44VareniclineVarenicline
BupropionBupropion
PlaceboPlacebo
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Studies I & II: CO-Confirmed 4-Wk Studies I & II: CO-Confirmed 4-Wk Continuous Quit Rates Wks 9–12Continuous 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 Bupropion Placebo
N=349 N=329 N=344 N=343 N=340 N=340
OR = odds ratio
*p<0.0001
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Varenicline WarningVarenicline Warning• Psychiatric symptomsPsychiatric symptoms
• AgitationAgitation
• Depressed moodDepressed mood
• Suicidal ideationSuicidal ideation
• Suicidal behaviorSuicidal behavior
• Warning: Warning: patients should be monitored and they and their families and patients should be monitored and they and their families and caregivers should be alerted to monitor for these symptomscaregivers should be alerted to monitor for these symptoms
• Advise patients and caregivers that the patient should stop taking CHANTIX and Advise patients and caregivers that the patient should stop taking CHANTIX and contact a health care provider immediately if agitation, depressed mood, or contact a health care provider immediately if agitation, depressed mood, or changes in behavior that are not typical for the patient are observed, or if the changes in behavior that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior (May, 2008)patient develops suicidal ideation or suicidal behavior (May, 2008)
• July 1: July 1: FDA has required the manufacturers of the smoking cessation aid varenicline (Chantix)…to add new Boxed Warnings and develop patient Medication Guides highlighting the risk of serious neuropsychiatric symptoms in patients using these products.
Nicotine Levels in a SmokerNicotine Levels in a Smoker
High
Withdrawal
Time
Nic
oti
ne
Le
vel
Carrier ProteinCarrier Protein
LinkerLinkerDrugDrug
IMMUNOGENIMMUNOGEN
++
BloodBlood BrainBrain
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Antibody Concentration Over Time Antibody Concentration Over Time Schedule 1 & Schedule 2Schedule 1 & Schedule 2
TQ
D
TQ
D
Schedule 1
Schedule 2
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52
Study Week
GMC Ab (µg/ml)
200 µg/Schedule 1
400 µg/Schedule 1
200 µg/Schedule 2
400 µg/Schedule 2
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12-Month12-MonthAbstinenceAbstinence
NicVAX NicVAX
High Antibody*High Antibody*
16%16%(n=10/61)(n=10/61)
p=0.03p=0.03NicVAX NicVAX
Low AntibodyLow Antibody
8%8%(n=11/140)(n=11/140)
p=0.49p=0.49
Placebo Placebo 6%6%(n=6/100)(n=6/100)
Continuous Abstinence at 12 Months by Continuous Abstinence at 12 Months by Anti-Nicotine Antibody LevelsAnti-Nicotine Antibody Levels
*Top 30% by AUC per protocol
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BUPROPRION AND SMOKING CESSATIONBUPROPRION AND SMOKING CESSATION
• Smokers• >18 years old• >15 cigarettes/day• Motivated to quit• Medically stable
• Four treatment groups• Placebo • Bupropion (150 mg bid)• Transdermal nicotine
(Habitrol) • Bupropion + TNS
• 2 week baseline7 week treatment2 week taper
• Smokers• >18 years old• >15 cigarettes/day• Motivated to quit• Medically stable
• Four treatment groups• Placebo • Bupropion (150 mg bid)• Transdermal nicotine
(Habitrol) • Bupropion + TNS
• 2 week baseline7 week treatment2 week taper Placebo TNS Bup Bup +TNSPlacebo TNS Bup Bup +TNS
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1010
2020
3030
4040
5050
6060
TreatmentTreatment
% abstinent% abstinent
Bupropion
• Seizures
• Neuropsychiatric symptoms
• Insomnia
• Allergic reactions
• July 1, 2009: FDA has required the manufacturers of the smoking cessation aid…bupropion (Zyban and generics) to add new Boxed Warnings and develop patient Medication Guides highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide.
Anti-depressants Evaluated for Anti-depressants Evaluated for Smoking CessationSmoking Cessation
• TricyclicsTricyclics– DoxepinDoxepin– ImipramineImipramine– NortriptylineNortriptyline
• MAO inhibitorsMAO inhibitors– MoclobemideMoclobemide– (*Selegiline)(*Selegiline)
Hughes, Stead and Lancaster Cochrane Database Syst Rev 2005
•SSRIsSSRIs–FluoxetineFluoxetine–ParoxetineParoxetine–SertralineSertraline
•AtypicalAtypical–BupropionBupropion–TryptophanTryptophan–VenlafaxineVenlafaxine
Effect of Selective Serotonin Reuptake Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) for Smoking CessationInhibitors (SSRIs) for Smoking Cessation
.1 .2 .5 1 2 5 10
Fluoxetine NiauraSpring
Fluoxetine Blondal
Paroxetine Killen
Paroxetine Killen
Sertraline Covey
Total
Favors TreatmentFavors Control
Hughes, Stead and Lancaster Cochrane Database Syst Rev 2005
Novel Treatments Novel Treatments for Smoking Cessationfor Smoking Cessation
Off label useOff label use– NortriptylineNortriptyline– ClonidineClonidine
New treatmentsNew treatments– BromocriptineBromocriptine– ReboxetineReboxetine– SelegelineSelegeline– TopiramateTopiramate– NaltrexoneNaltrexone– EVT302EVT302– DianiclineDianicline– GabapentinGabapentin– GW468816GW468816– MemantineMemantine
–SibutramineSibutramine–NalmefeneNalmefene–EszopicloneEszopiclone–MecamylamineMecamylamine–PhospholipidPhospholipid–RimonabantRimonabant–SurinabantSurinabant–TaranabantTaranabant–Lis-dexamphetamineLis-dexamphetamine–GuanfacineGuanfacine
–VaccineVaccine