Tobacco Dependence and Its Treatment

Taru Hannele Kinnunen, PhDHarvard Medical School

Harvard School Dental Medicine

Department of Oral Health Policy and Epidemiology

Harvard Medical School Alumni Day PlenaryJune 2006

Tobacco Use and Oral Cavity

TOBACCO USE

Pre-cancerous Lesions

Oral Cancers

•Gingivitis•Periodontitis•Acute Ulcero-Necrotic Gingivitis

•Teeth colorations•Halitosis•Sense of taste/smell•Chronic Sinusitis

Consequences in implantology

Consequences in wound healing

Tobacco Dependence –a Chronic Syndrome

ICD-10: 17 Mental and behavioral disorders due to use of tobacco17.1 Harmful use 17.2 Dependence syndrome 17.3 Withdrawal state

DSM-IV-TR: Nicotine Use Disorder305.1 Nicotine Dependence 292.0 Nicotine Withdrawal

Dental codeD1320 Tobacco counseling for the control

and provision of oral disease

Smoking in Perspective• Kills more than 430,000 Americans each year

• 25% of adult Americans smoke

• 3,000 children and adolescents become regular tobacco users every day

• Causes cancer, heart disease, stroke, pulmonary disease, and adverse pregnancy outcomes

• Adds $50 billion in direct health costs each year

• One-third of all tobacco users in U.S. will die prematurely

Health Consequences of Smoking Cessation

• Smoking is number 1 preventable cause of death

• Treating tobacco dependence– cost-effective– significant measure in primary and secondary

prevention• Smoking cessation results in many positive

health consequences– most immediately and substantially coronary

heart disease and other cardiovascular diseases (CVD)(USDHH. Women and smoking: A report of the Surgeon General 2001.), (Benowitz 2003, Kinnunen Mustonen 2004)

Treatment after CHD: Reduction of the Mortality Risk

39%

29%

23%

23%

15%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45%

Smoking Cessation

Statins

Beta-blockers

ACE-Inhibitors

Aspirin

JAMA, 2003

BMJ, 2000

BMJ, 1999

Lancet, 2000

BMJ, 2002

Difficulty in Quitting

• 70% of tobacco users would like to quit

• Less than 10% succeed in a given year

• Long term or permanent abstinence may be achieved after several attempts.

• Only 5-10% tobacco users are not nicotine dependent

Nicotine Dependence

Copyright © 2002, TK. All rights reserved.

• Physiological dependence neurobiology:

neuromodulation and neuroadaptation

genetics

positive and negative reinforcment

withdrawal

• Conditioning/Learning highly conditioned behavior

20 cigarettes x 10 puffs= 200 repetitions

slips, relapse

• Sensory aspect of smoking

Clinical Guidelines for TX

Intensity: Dose-response

Type: Individual/Group

Content• Problem solving/Skills

training

• Intra-treatment social support

• Extra-treatment social support

First-line therapies:

• NRT (gum, patch, lozenge, inhlaler, spray)

• BupropionSR*(Zyban, Wellbutrin)

Second-line therapies:

• nortriptyline• clonidine

Combination therapies• NRT+NRT• Bupropion SR + NRT

New Therapies• Varenicline (Chantix)

CounselingBehavioral Tx

Pharmacological Tx

1-year Abstinence in Studies with NRT and Behavioral Counseling

0

20

40

60

80

100

% A

bst

inen

t

1-week 16-weeks 1-year

Ex_NicGum CG_NicGum NicGum0

10

20

30

40

50

60

70

80

90

100

1-week 16-week 1-year

NicGum

1992-1995

1999-2002

(Garvey & Kinnunen, NIDA)

(Kinnunen, NIDA)

From Tobacco Plant to Cigarettes

Nicotine Dependenceself-administrationwithdrawal symptoms

Acute Exposure of Nicotine

• Tobacco smoke contains concentrated amounts of nicotine•Fast delivery to brain•Stimulation and release of Ach• Modulation of other neurotransmitters

•Neuromodulation

nicotine receptornAChR

nicotine molecules from

tobacco smokeAcetylcholine

ACh

Synapse

AcetylcholineACh

nAChR

Nicotine

Synapse

Cholinergic neuron

Dopaminergic neuron

Most Effects are Mediated by Nicotinic Receptors

(nAChRs)

Subtype α4β2

17 subtypes (α4β2, α7)

Minutes

Incre

ase i

n n

ico

tin

e c

on

cen

trati

on

( n

g/m

l )

Cigarette

Gum 4mg

Gum/ Lozenge 2mg

Inhaler

Nasal sprayPatch

5 10 15 20 25 30

0

2

4

6

8

10

12

14

Plasma Nicotine Concentrations for Smoking and NRT

Source: Balfour DJ & Fagerström KO. Pharmacol Ther 1996 72:51-81.

Individualizing Treatment Double Blind Placebo Controlled Study

Individualized Treatment

50%

Nicotine

Replacement

21 mg

Nicotine

Patch

42 mg

Nicotine

Patch

100%

Nicotine

ReplacementPlacebo

Patch

Garvey & Kinnunen

2001-2005 NIDA

Does 100% replacement of nicotine using nicotine patches lead higher abstinence rates?

Potential Factors ImpactingCotinine Levels Obtained from

Nicotine Patches• Patch Dose

• Baseline Cotinine Level

• Level of Dependence on Nicotine

• Pack years (packs/day x no. of years smoked)

• Cigarettes per day smoked

• Age

• Sex

• Race

• Body Mass Index

• Clearance (Baseline cot./cigs per day)

• Type of cigarette (Menthol/ NonMenthol)

0 25 50 75 100 125 150 175 200 225 250 275 300 325 350 375

Days Post - Cessat ion

0

10

20

30

40

50

60

70

80

90

100

Pe

rce

nt

Ab

stin

en

tAbstinence Patterns by Treatment Group

100%

50%

0 mg

21 mg

42 mg

p = .05

Garvey et al., 2006

Improving Treatment

• Adjuncts to behavioral and pharmacological treatments may be one solution

• Tailoring treatments to specific population– > WOMEN– Women more fearful of gaining weight– Women report more often negative affectivity

and stress after quitting– Depression and smoking cessation have a

strong association and depression is more common among women

Aerobic Exercise and NRT for Female Smokers - Study

DA12503-01_04 Kinnunen (1999-2003)

•sedentary smokers•ages 18-55•no cardiac Hx•over 5 cigarettes/day

Equal Contact Group (n=56)Wellness Counseling (2 x week)3 wks prequit 16 wks postquitNicotine gumBrief Counseling

Experimental Group (n=92)Aerobic Exercise (2-3 x week)3 wks prequit 16 wks postquitNicotine gumBrief Counseling

Standard Care Control Group (n= 34)_Nicotine gumBrief Counseling

1-Year Smoking AbstinenceCumulative Proportion Surviving (Kaplan-Meier)

Exercise and NRT Study

0 50 100 150 200 250 300 350 400 450

Time

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ula

tive P

roportio

n S

urv

ivin

g

Standard care

Exercise

Wellness

Exercise and Wellness groups were

significantly different (p<.05) from

the Standard Care group

Kinnunen et al, 2005, Noc Tobacco Res

Conclusions• Exercise promoted smoking cessation beyond

standard care• Exercise had favorable impact on mood • Poor adherence to exercise regimen among

those who had:

Higher nicotine dependence

Higher body mass index

Higher depression level

Higher stress level

Lower education

Korhonen, Kinnunen et al., 2005, Tob Induced Dis

Increasing Adherence to TX• Optimizing settings

(home vs. facility)

• Reducing barriers

• Increasing adherence with counseling

• Continuing NRT

• Mapping out CVD risk profile better and assessing harm reduction

NIDA –DA12503

Future Directions

• Expanding and enhancing behavioral treatments

– (Front-loaded counseling Garvey & Kinnunen, NIDA)

• Discovering new and new combinations of pharmacotherapy

• Immunotherapy – Nicotine vaccine

• Harm reduction

Nicotine Vaccine

• Nicotine vaccine is designed to elicit the production of nicotine antibodies.

If someone smokes after being immunized, the antibodies bind with nicotine molecules in the bloodstream and prevent them from entering the brain where nicotine receptors are located.

Previous research has shown that, since antibody levels rise slowly, smokers lose the nicotine reward gradually, avoiding withdrawal symptoms.

"Quitting smoking is easy.

I've done it a thousand times.“- Mark Twain