Jill Williams, MD

UMDNJ-Robert Wood Johnson Medical School
Alcohol Medical Scholars Program

Revised March 26, 2007

 

Assessment and Pharmacological Treatment of Tobacco Dependence

< Slide 1>

 

I. Introduction

            A. Tobacco use is common and has many devastating effects < Slide 2>

1.  ~70 million cigarette smokers in US

2.  Number one preventable cause of morbidity/ mortality in US

3. > 500,000 premature deaths/year from tobacco[1]

4. 50,000 deaths (in nonsmokers) from environmental tobacco smoke[2]

5. Tobacco and nicotine differ - Tobacco is the harmful part of smoking, not nicotine.  It’s the smoke that kills

                                   

            B. Many smokers want to quit and treatments improve outcomes < Slide 2>

            1. 41% of smokers try to quit each year

2.  Assessment guides treatment

3.  Brief advice from a physician increases quitting

4.  Treatments double success rates

                       

            C. This lecture will cover  < Slide 3>

1.      Epidemiology and consequences

2.      Nicotine pharmacology

3.      Assessment

4.      Pharmacological treatments

 

           

II. Epidemiology and consequences of tobacco use < Slide 4>

A. Epidemiology

                        1. >1 billion tobacco users worldwide

                                    a. ↑ in developing regions (China, India, Africa, S. America)

                                    b. Stable or ↓ in developed nations

2. ~23% of US population smokes cigarettes < Slide 5>

            a.  3% of physicians[3]

            b. 70% with mental illness or SUD [4],[5]

            c. Smoking prevalence ↓ 1960s, but stable~ last 15 years

                        3. Tobacco forms

a. Cigarettes > 95% of all tobacco use

                                    b. Cigar smoking

                                                1). Non-daily use patterns

2). ~5% prevalence; increased > 50 percent since 1990s

3). ↑ in youth, women, minority groups

                                    c. Chewing tobacco

                                                1). Loose leaf or snuff

2) 3.5% prevalence (Men use 7x > women) [6]

                        4.  Prevalence ↑ in lower SES

5. Males > females[7]; women ↑since 1950s (lung cancer deaths > breast cancer deaths since 1987) [8]   < Slide 6>

6.  Recent ↑ in youth smoking (“Pediatric epidemic”)  < Slide 7>

a.   Initiation during grades 6-9 (ages 11-15).

b.      90% of all smokers start before age 18

c.       If begin < 16, 1.6x be dependent [9]

d.      5 million US smokers aged 12-17 years

                       

B. Morbidity and mortality < Slide 8>

1. Half of smokers die from a tobacco-caused disease (~ 1 in 5 US deaths)

2. Cancer

a. ~90% of lung cancers from smoking[10]

1). #1 cause of cancer deaths in US

2). 15% 5-year survival rate

b. Other types   < Slide 9>

{SOURCE: 2004 Surgeon General Report on the Health Consequences of Smoking}

1). Oral cancers (lip, tongue, mouth, and larynx)

2). Esophagus, cervix, bladder, pancreas, and kidney

3. Causes ~100% COPD

4.      2x ↑ death from stroke/ coronary heart disease

 

C. Other consequences

1. Costs > $100 billion annually

a. $50 billion in medical costs

b. $50 billion lost productivity

                        2.  Primary cause of fatal house fires

 

III. Assessment and treatment

A. Components of tobacco smoke < Slide 10>

            1. Smoke > than 4000 chemicals

                        a. Carbon monoxide

b. Other toxins

1). Hydrogen cyanide

2). Formaldehyde

3). Ammonia

2. Smoke > 60 carcinogens (benzene, cadmium, nitrosamines, polycyclic aromatic hydrocarbons (PAH))

3. Environmental Tobacco Smoke (ETS) < Slide 11>

a. Smoke from cigarettes of others

b. Class1A carcinogen, same class as asbestos

            c. 50,000 additional deaths/ year in non-smokers (3000 lung cancer)

4.      Nicotine pharmacology depends on delivery route < Slide 13>

a.        Short half-life (2 hours)

b.      Best absorption when smoked[11]

            1). Cigarettes (smoking) “perfect” drug delivery device

            2)  Reaches brain in 10 sec[12]

            3). Most reinforcing form

            c. Binds to nicotinic cholinergic receptors

            d. Arterial levels 6-10x higher than venous

            e.  Metabolized to cotinine in liver

5. Nicotine researched for possible therapeutic effect < Slide 15>

            a. Ulcerative colitis[13]

            b. Alzheimer's disease

            c.  Parkinson's disease

            d. Tourette's syndrome[14]

            e. Attention deficit disorder[15]

            f.  Schizophrenia[16]

6. Nicotine safety < Slide 16>

            a.  Not a carcinogen

            b.  Not a risk factor for cardiovascular events, even in people with         cardiovascular disease [17], [18], [19]

            c. Risk-benefit ratio supports of using nicotine products over using         tobacco[20]

            d. Smokers misinformed re: safety/efficacy of nicotine[21]

                                                           

B. Assessment guides treatment

1. DSM IV criteria [22] < Slide 18>

            a.  Nicotine dependence

1). DSM not list abuse: Clinically significant psychosocial problems rare

                        2). ≥ 90% smokers meet dependence criteria[23]

                        3). 3 or more of 7 DSM dependence criteria

a). Persistent desire or unsuccessful efforts to cut down or control use

b) Activities given up or reduced

c). Use despite a physical or psychological problem

d). Tolerance

e). Withdrawal

b.  Nicotine withdrawal < Slide 19>

                        1) Symptoms

                                                      a). Dysphoric or depressed mood

b). Insomnia

c). Irritability, frustration or anger

d). Anxiety

e). Difficulty concentrating

f). Restlessness

g). Decreased heart rate

h). Increased appetite or weight gain

                        2). Duration

a). Most severe 1-3 days after quitting

b). Can last 4 weeks

2. Heaviness of smoking index = measure dependence severity [24]  < Slide 20>

a.  Number of cigarettes per day (cpd) smoked

                        b.  Time to first cigarette (TTFC)

                                    1). Smokers awaken in nicotine withdrawal

2). Smoking ≤ 30 minutes of awakening = moderate dependence

3). Smoking ≤ 5 minutes of awakening = severe dependence

 

C. Motivation to quit < Slide 21>

1. 70% of smokers want to quit

2. Few quit successfully without treatment

a. 33% of self-quitters remain abstinent for 2 days

b. < 5% successful

 

D. Provider’s role in treatment < Slide 22>

{SOURCE: PHS Guidelines, Treating Tobacco Use and Dependence: Clinical Practice Guidelines,              US Dept Health and Human services}

1.      Use 5As for primary care settings (ask, advise, assess, assist, and arrange)

                        a.  Ask—identify all tobacco users at every visit

                        b. Advise—urge users to quit

                        c. Assess—determine willingness to quit

                        d. Assist—aid in quitting

                        e. Arrange—follow-up

2.      Brief physician advice quitting [25]

3.      More physician counseling is better

a. 10% quit rates with < 3 minutes

b. 20% quit rates >10 minutes

 

E. Treatments ↑ long-term abstinence

1.      Tobacco dependence = chronic condition

            a. < 25% quit successfully on their first attempt

            b.  Usually 8 quit attempts before successful[26]

2. Pharmacotherapy a first line treatment [27]

            a. Doubles success

b. Recommended for all who try to quit, unless contraindications

                        c. Works even without psychosocial treatments [28]

d. Best outcomes: meds +  psychosocial[29]

 

IV. Rationale for pharmacotherapy [30] < Slide 24>

            A.  ↓ or eliminate withdrawal

            B.  ↓ reinforcement by nicotine [31],[32]

            C.  ↓ weight gain when quitting

            D.  Unlearn smoking behaviors

            E.  Manage negative mood

F. Cost-effective [33],[34]

1. Treatment cost  per smoker $165 17

2. More cost-effective than mammography, anti-HTN drugs

                       

V. First-line/ FDA approved pharmacological treatments          

            A.  Poor absorption from nicotine replacement medication (NRT)[35],[36]  < Slide 26>

                        1.  Nicotine absorption is pH dependent

                        2.  Lower dose delivered

                        3.  Less reinforcing than smoking [37]

                        4.  Poorly absorbed orally

                        5.  Poor compliance and under dosing  common [38]

6.  Relative contraindications to NRT 11 < Slide 27>

a. Few unable to take nicotine

b. With caution in selected populations

1). Recent MI

2). Uses < 10 cigarettes per day

3). Pregnant/breastfeeding

4). Adolescents (Not FDA approved)

7.       Side effects NRT

a. Usually mild

b. Local irritant at site of use

c. Systemic side effects less common

1).Dizziness

2). Nausea

3). Headache

8. Start NRT on the quit date (QD)

 

B.  Nicotine patch[39]      < Slide 28>

1.      Slow onset of action

a.       30 min to onset

b.      6 h to peak

2.      Continuous delivery

a.       24 or 16 hour dosing

b.      Night wearing relieves morning craving but disturbs sleep

c.       Given with gradual taper

3.      Passive dosing

a.       Easy to use

b.      Best compliance44

c.       No response to acute craving

4.      Side effects

a.       Skin

1). Itching, tingling at patch site

2). True rash rare

b.      Sleep disturbance, abnormal dreaming

5.      Availability and cost

a.       OTC

b.      $50 for 2 week supply

 

C.     Nicotine gum < Slide 29>

1.      Buccal absorption

a.   20-30  min onset of action

b.  Reduced with acidic beverages (soda, coffee)

c.   Bite and park method improves absorption and reduces side effects

2.      Side effects

a.       Mild- peppery taste

b.      Throat irritation

c.       Dyspepsia

d.      Jaw soreness

3.      Dosing

a.       1 piece an hour

b.      ↑ for cravings (up to 24 pieces/ day)

c.       6 weeks than taper

d.      Longer more helpful

e.       Dose: 2mg < 25 cpd; 4 mg> 25 cpd

4.      Limitations

a.       TMJ

b.      Dental problems, edentulous

5.      Availability and cost

a.       OTC

b.      $50 for 2 week supply

c.       Generics available ($25-$35)

 

D.     Nicotine lozenge  < Slide 30>

1.      Buccal absorption (similar to gum, more discreet)

a.       Reduced with acidic beverages

b.      Dissolve; don’t chew (15 min)

2.      Side effects

a.       Mild

b.      Throat irritation

3.      Dosing

a.       1 piece an hour, for cravings

b.      Max 20 per day

c.       6 weeks than taper

d.      Dose based on TTFC instead of number of cpd

e.       Dose: 2mg  if > 30 mins TTFC ; 4 mg< 30 mins TTFC [40]

4.      Availability and cost

a.       OTC

b.      $80 for 2 week supply

c.       No generics

5.      Limitations: none

 

E.      Nicotine inhaler  < Slide 31>

1.      Buccal absorption

a.       Oral puffer; inhaler misnomer

b.      Reduced with acidic beverages

c.       Hand to mouth activity helpful for some

2.      Side effects

a.       Mild

b.      Throat irritation

c.       Cough

3.      Dosing

a.       6-16 cartridges per day

b.      Puff for 20 min

4.      Limitations - frequent and continuous puffing  (80 puffs =1 cigarette)

5.      Availability and cost

               a.   Prescription

b.   Packaged #42 or #168 cartridges (approx $1/cartridge)

                        c.   Not covered by all insurance

 

F.      Nicotine nasal spray  < Slide 32>

1.      Rapid delivery though nasal mucosa

a.       Onset  in  minutes[41]

b.      Modest peak in 10 minutes

2.      Side effects[42]

a.       Moderate- can lead to discontinuation

b.      Sneezing

c.       Runny nose, watery eyes

d.      Burning in nasal mucosa

e.       Risk for bronchospasm (h/o asthma)

f.        Tachyphylaxis- remit with continued use

3.      Dosing

a.       One spray each nostril = 1 dose (2 sprays)

b.      Minimum  8 doses/day

c.       1-2 doses/ hr

d.      40 doses/ day max

4.      Limitations

a.       Side effects

b.      High early discontinuation

c.       Dependence in 30% + using >6 months [43], [44]

5.      Availability and cost

a.   Prescription

b.   Packaged as 4 -10mL bottles

c.   Cost: $5/day; $45/ bottle

d.   Not covered by all insurance

 

G.     Bupropion < Slide 33>

1.      Pharmacology

a.       Zyban SR= Wellbutrin SR

b.      Accidental discovery as smoking aid

c.       Activating, non-sedating antidepressant

d.      Effects on DA and NE

e.       Effects as nicotinic receptor antagonist [45],[46]

2.      Side effects

a.       Mild to moderate

b.      Headache

c.       Anxiety, agitation

d.      Dry mouth

e.       Insomnia

3.      Dosing

a.       150 mg x 3-7 days, then ↑ up to 300mg daily

b.      Start 2 weeks before quit date

c.       7-12 weeks maintenance up to 6 months

d.      300 mg dose associated with least weight gain (1-2 lbs at 6 mos) [47]

4.      Limitations/ contraindications

a.       Seizure

b.      Eating disorder

c.       Current use of Wellbutrin or MAO inhibitors

5.      Availability and cost

a.       Prescription

b.      Reimbursable as Wellbutrin, often not as Zyban

c.       Cost $3 per day

 

H.     Efficacy < Slide 34>

1.      Nicotine replacement

                                                                               a.      Doubles the likelihood of success in stopping smoking as compared with placebo or no NRT 23

                                                                              b.      Meta-analysis of 110 randomized trials, 35,000 patients.  Odds ratio of 6 months abstinence compared to placebo 25

1). Overall 1.74

      2). Gum 1.66

      3). Patch 1.74

4). Inhaler 2.08

5). Nasal spray 2.27

6). Lozenge 2.08

                                                                               c.      Success rates 25-30% at 12 weeks

                                                                              d.      No differences in outcomes in a randomized trial of 4 types of NRT (gum= patch= nasal spray= inhaler) [48]

2.      Bupropion 

                                                                               a.      Efficacy comparable to NRT [49] or ? slightly higher [50]

                                                                              b.      Efficacy independent of antidepressant properties [51],[52]

3.      Patient preference, cost, tolerability

4.      Combination therapy may improve outcomes

                                                                               a.      Nicotine combinations

1).  Sustained plus immediate acting for craving relief[53]

2).  Improves abstinence outcomes [54]

3). Greater withdrawal relief [55]

                                                                              b.      Nicotine plus bupropion

   1). No medication interactions/ precautions

2). Commonly given clinically

3). Efficacy unknown, not well studied

 

I.        Varenicline < Slide 35>

1.      Partial nicotine agonist [56]

                                                                               a.       Eliminate reward from smoking

                                                                              b.       Prevent withdrawal symptoms

                                                                               c.       Not addicting

                           2. 1mg BID dose superior to placebo or bupropion in 12 week trials[57],[58]

                           3.  Additional 12 weeks prevented relapse in continuation study[59]

                           4.  Most common side effects

                                       a.   Nausea

                                       b.   Headache

                                       c.   Insomnia

                                       d.   Abnormal dreams

 

VI. Conclusions < Slide 36>

1.  All practitioners should treat tobacco

2.  Pharmacotherapy doubles the success rates in making a quit attempt and should be used in all smokers trying to quit

            3.  Six FDA approved treatments are effective and well tolerated


 



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