Effective Treatments for Tobacco Dependence

Abigail Halperin MD, MPH Director, University of Washington Tobacco Studies Program

Ken Wassum Associate Director of Clinical Development and Support

Quit for Life Program, Alere Wellbeing

April 2012

Effective Treatments for Tobacco Dependence: Overview

n  Why does treatment matter?

n  Why do smokers keep smoking?

n  What smoking cessation treatments are effective?

n  Behavioral

n  Pharmacological

n  Role of health care providers

WHY TREATMENT MATTERS n  Tobacco use is the #1 preventable cause of death n  Stopping tobacco use reduces health risks n  Tobacco prevention works slowly n  Tobacco use is an addictive disorder n  Tobacco treatment synergizes with tobacco control

policies

WHY DO SMOKERS KEEP SMOKING?

Individual Perspective Tobacco Addiction Triangle

Epidemiologic Model of Tobacco

Addiction and Its Control

AGENT

OF ADDICTION & DISEASE

VECTOR HOST

Tobacco Products

Tobacco Industry Tobacco User

Orleans & Slade, 1993; Giovino 2002

Population Perspective

WHY DO SMOKERS KEEP SMOKING?

n  Pharmacologic nicotine dependence

DOPAMINE

Saturation of nicotinic receptors with smoking in smokers vs. non-smokers (Brody et al., Arch Gen Psych 2006)

WHY DO SMOKERS KEEP SMOKING?

l  Irritability, anger, impatience l  Restlessness l  Difficulty concentrating l  Insomnia l  Anxiety l  Depressed mood l  Increased appetite

n  Pharmacologic nicotine dependence → Craving (nicotine “hunger”)

→ Nicotine withdrawal symptoms

WHY DO SMOKERS KEEP SMOKING?

n  Pharmacologic nicotine dependence

■  Psychological factors

•  Cues (meals, alcohol, other smokers)

•  Coping with stress, emotions (anger) •  Depression, other substance use

WHY DO SMOKERS KEEP SMOKING?

n  Pharmacologic nicotine dependence

■  Psychological factors

■  Behavioral habits

•  Hand to mouth action •  Oral stimulation/satisfaction

•  Daily routines/rituals

THE CHALLENGE FOR TREATMENT

n  We have effective treatments, but we still need better ones, AND

n  We need to deliver the treatments we have to more of the smokers who need them •  70% of smokers want to quit; 50% try

•  Only 5% succeed unassisted vs. 25-30% with help •  Only 25% use any form of help

•  HCPs poorly trained to treat tobacco

•  Health care systems do not prioritize tobacco tx

SMOKING CESSATION METHODS 2008 US Public Health Service Guidelines

■  Effective treatments

■  More is better, but even brief intervention works ■  Treating tobacco is highly cost-effective ■  Pharmacotherapy reduces withdrawal while smoker learns to live without cigarettes

l  Counseling

l  Pharmacotherapy

l  Combination - better than either one alone

COUNSELING – Content

■  Smokers who want to quit ■  Cognitive-behavioral counseling ■  Practical skills—Quit plan (STAR) ■  Social support (intra-tx and extra-tx) ■  Encourage medication use and adherence

■  Smokers who are not ready to quit ■  Motivational interviewing ■  Teachable moments

COUNSELING – Method of Delivery

■  In-person * - one-on-one or group

■  By telephone * - proactive quitlines

■  Self-help materials – little efficacy

■  Newer technologies ■  Web-based – evidence is growing but not definitive

■  Text-messaging – one randomized trial (Lancet 2011)

■  Social media – little evidence

* Endorsed as effective by 2008 USPHS Guideline Update

TELEPHONE QUITLINES

n  Definition

Proactive multi-session counseling by phone

n  Advantages Convenience Privacy

n  Effective (pooled OR 1.4, 95% CI 1.3-1.6)*

n  Quitlines can also provide medication Facilitate access to free or low-cost medications Strategy for promoting calls to a quitline

*Stead LF et al. Tobacco Control 2007;16(suppl 1):i3

PHARMACOTHERAPY 1st Line - 2008 US Public Health Service Guidelines

n  Nicotine replacement OR

l  Skin patch 1.9

l  Gum 1.5

l  Oral inhaler 2.1 l  Nasal spray 2.3

l  Lozenge 2.0

n  Bupropion SR (Zyban,Wellbutrin SR) 2.0

n  Varenicline (Chantix/Champix) 3.1

0

24

68

1012

1416

18

0 10 20 30 40 50 60 70 80 90 100 110 120

Time post administration (min)

Pla

sma

nico

tine

leve

l (ng

/mL)

Cigarette (1-2 mg)

Nasal spray (1 mg)

Gum (4 mg)

Patch (21 mg)

PLASMA NICOTINE LEVELS

Cigarettes vs. Nicotine Replacement Products

NICOTINE REPLACEMENT

Long-acting, slow onset → skin patch

Short-acting Intermediate onset → oral (gum, lozenge, inhaler)

More rapid onset → nasal (spray)

l  Constant nicotine level to avoid withdrawal l  Simplest to use, best compliance l  User has no control of dose

l  User controls dose, can titrate to need l  Nicotine blood levels fluctuate more l  Requires more training to use properly

New Ways to Use

NICOTINE REPLACEMENT (Supported by evidence and USPHS*)

n  * Combine short- and long-acting forms “Patch plus” regimen

n  * Extend treatment to prevent relapse

n  Start NRT 2 weeks before quit date

n  Reduce to quit strategy

BUPROPION SR (Zyban, Wellbutrin SR)

§  Doubles cessation rate; mechanism independent of its antidepressant effect

§  Reduces post-cessation weight gain

§  Quit rates higher if add counseling

§  Reduces seizure threshold (risk: 1/1000)

VARENICLINE

§  Binds selectively to the α4β2 nicotinic receptor, which mediates nicotine dependence

§  Dual mechanism of action §  Partial agonist

Stimulates receptor to treat craving, withdrawal

§  Antagonist Prevents nicotine from binding to the receptor → Blocks reward; reduces reinforcement of smoking

NH

NN

VARENICLINE SAFETY The Dilemma

n  Smokers have an increased risk of suicide.

n  Stopping smoking produces nicotine withdrawal symptoms (depressed mood, anxiety, and irritability)

n  When these symptoms occur in a smoker who is stopping smoking on varenicline, is it the drug or quitting smoking that causes the symptom?

n  Case reports cannot answer this question.

n  Clinical trials of varenicline detected no excess of depression or suicidal thoughts, but these studies did not include patients with mental illness.

FDA Public Health Advisory July 2009

n  “Chantix (varenicline) and Zyban (bupropion) have been associated with reports of changes in behavior such as hostility, agitation, depressed mood, and suicidal thoughts or actions.”

n  “FDA is requiring the manufacturers of both products to add a new Boxed Warning:

People who are taking Chantix or Zyban and experience any serious and unusual changes in mood or behavior or who feel like hurting themselves or someone else should stop taking the medicine and call their healthcare professional right away. Friends or family members …”

VARENICLINE SAFETY Cohort study (Gunnell et al, BMJ 2009)

n  UK General Practice Research Database n  Population based data: 3.6 million patients in 500 practices n  Data from electronic medical records

n  Sample: Patients starting medication (9/06 – 5/08) n  NRT (n=63,265) n  Bupropion (n=6422) n  Varenicline (n=10,973)

n  Outcome: Rates of suicide, suicide attempt, suicidal thoughts, and new antidepressant therapy

n  Results: No evidence of increased risk of suicidal outcomes for varenicline vs NRT, bupropion vs NRT

VARENICLINE SAFETY The Bottom Line

n  Varenicline may increase risk of psychiatric symptoms in some patients. The potential risk is not yet well defined.

n  Prescribing varenicline, like prescribing any drug, requires balancing risks and benefits. - Varenicline is one of the most effective drugs available to treat tobacco dependence - Continuing to smoke is clearly hazardous

n  In most cases, the benefits of varenicline outweigh the risks

Which drug is most effective? Meta-analysis for 2008 USPHS Guideline

Drug Estimated OR (95% CI)

Nicotine patch 1.0 (reference) Other nicotine products or bupropion

Not significantly different from nicotine patch

Varenicline 1.6 (1.3-2.0)

Combinations Long-term patch + gum or nasal spray

1.9 (1.3-2.7)

Patch + bupropion SR 1.3 (1.0-1.8)

Two head-to-head randomized trials Piper, Arch Gen Psychiat 2009; Smith, Arch Int Med 2010

n  Tested five drug treatments (vs placebo) l  Monotherapy: Patch, lozenge, bupropion l  Combos: Patch + lozenge, bupropion + lozenge

n  Tested drugs in two settings l  Clinical trial (on-site counseling) l  Primary care clinics (using state quitline)

n  Results l  Each drug was better than placebo l  Combinations were better than monotherapy l  No combination was better than the other

PHYSICIAN INTERVENTION

n  Routine advice to quit is effective á Odds of quitting by 66% (vs. no advice) *

n  Brief counseling is more effective á Odds of quitting by 37% (vs. advice) *

n  Brief intervention by other clinicians are also effective (slightly less than by MD)

* Cochrane reviews

5As BRIEF COUNSELING MODEL 2000 U.S. Public Health Service Guidelines

l  ASK all patients about smoking l  ADVISE all smokers to quit l  ASSESS smoker’s readiness to quit

l  ASSIST smokers to quit (counsel + meds)

l  ARRANGE follow-up care

5As BRIEF COUNSELING MODEL Team Approach or AA&R

l  ASK Done by office staff (ie, vital sign)

l  ADVISE Core physician role l  ASSESS Core physician role

l  ASSIST In office or community resource

l  ARRANGE Refer for f/u support (ie, quitline…)

5As BRIEF COUNSELING MODEL ASSIST: Develop a Quit Plan (STARS)

l  SET Quit date (within 2 weeks)

l  TELL Family, friends, co-workers l  ANTICIPATE Challenges

l  REMOVE Tobacco products, matches, etc

l  SUPPLEMENTAL Materials for support (may include medication instructions, IVR, website, etc)

5As BRIEF COUNSELING MODEL ARRANGE: Follow up

l  Discuss medication use questions or problems l  Ask about successes and lapses l  Use learning and skill building opportunities l  Provide support and encouragement l  Offer guidance for problem solving l  Adjust quit plan as needed

Discussion and Q & A with Ken Wassum

Acknowledgements: Slides adapted with permission

from Nancy Rigotti, MD

Follow-up: Interactive training modules for treating

tobacco use and dependence available at: http://iml.dartmouth.edu/education/dsr/