1 smoking cessation: what works and why… a medical model stephen i rennard university of nebraska...

Post on 03-Jan-2016

219 Views

Category:

Documents

0 Downloads

Preview:

Click to see full reader

TRANSCRIPT

1

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

2

3

4

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)

5

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

6

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

7

Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning

Nicotine

Increased ReceptorsIncreased Occupancy

Withdrawal

8

Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning

Cues

9

Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning

Cues

Conditioned Response

10

Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning

Nicotine

Cues

Conditioned Response

11

Nicotine: Addiction and Nicotine: Addiction and ConditioningConditioning

Nicotine

Increased ReceptorsIncreased Occupancy

Withdrawal

Cues

Conditioned Response

12

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

16

17

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

18

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

21

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

22

33

44VareniclineVarenicline

BupropionBupropion

PlaceboPlacebo

22

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

23

24

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

28

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

29

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

30

31

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

00

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

top related