ACKNOWLEDGEMENTS

1
ACKNOWLEDGEMENTS

• Washington State Tobacco Prevention Resource
  Center
• Karen Hudmon, DrPH, RPh and Rx for Change
• Sebastien Fromont, MD Sharon Hall, PhD
• Grant funding California Tobacco Related Disease
  Research Program (13KT-0152) National Institute
  on Drug Abuse (K23 DA018691, P50 DA09253)
  American Cancer Society (IRG AC-08-04)
• No commercial conflicts of interest

2
Magnitude of the Problem the Need for Treatment
3
TOBACCO USE in PSYCHIATRIC POPULATIONS

• Nicotine dependence most prevalent substance
  use disorder among psychiatric patients
• Smoking rates 2 to 4 xs that of the general
  population (Hughes, 1993 Poirier, 2002)
• The mentally ill comprise 44 to 46 of the US
  tobacco market (Lasser et al., 2000 Grant et
  al., 2004)
• 175 billion cigarettes and 39 billion in annual
  sales (USDA, 2004)

4
TRENDS in ADULT SMOKING US, 19552004
Trends in cigarette smoking among persons aged 18
or older
20.9 of adults are current smokers
Male
Percent
Female
22.9
17.5
Graph provided by the Centers for Disease Control
and Prevention. 1955 Current Population Survey
19652004 NHIS. Estimates since 1992 include
some-day smoking.
5
SMOKING RATE by PSYCHIATRIC HISTORY
41.0 Overall
National Comorbidity Survey 1991-1992 Source
Lasser et al., 2000 JAMA
Active
6
SMOKING in CALIFORNIA
Acton, Prochaska, Kaplan, Small Hall. (2001)
Addict Behav Prochaska, Gill, Hall. (2004)
Psychiatric Services
7
TOBACCO KILLS

• 1 of 2 chronic smokers will die from smoking
  related illnesses (USDHHS, 2000).
• The mentally ill are at elevated risk for
  respiratory and cardiovascular diseases and
  cancer, compared to age-matched controls (Brown
  et al., 2000 Bruce et al., 1994 Dalton et al.,
  2002 Himelhoch et al., 2004 Lichtermann et al.,
  2001 Sokal et al., 2004).
• Current tobacco use is predictive of future
  suicidal behavior, independent of depressive
  symptoms, prior suicidal acts, and other
  substance use (Breslau et al., 2005 Oquendo et
  al., 2004, Potkin et al., 2003).

8
COMPARATIVE CAUSES of ANNUAL DEATHS in the UNITED
STATES
Individuals with mental illness or substance use
disorders
Number of Deaths (thousands)
AIDS Obesity Alcohol Motor
Homicide Drug Suicide Smoking

Vehicle Induced
Source CDC
9
HEALTH RISKS ASSOCIATED with CHRONIC TOBACCO USE

• Cardiovascular disease
• Lung Disease
• Cancers
• Delayed healing recovery after surgery
• Dyslipidemia
• Hypertension
• Macular degeneration
• Cataract
• Osteoporosis

• Periodontal disease
• Sexual dysfunction
• Reduced fertility in women
• Poor pregnancy outcomes
• SIDS, child asthma
• Mental Illness
• Suicidal Behavior
• Depression
• Anxiety
• Psychosis

10
COMPOUNDS in TOBACCO SMOKE
An estimated 4,800 compounds in tobacco smoke
Gases (500 isolated)
Particles (3,500 isolated)

• Carbon monoxide
• Hydrogen cyanide
• Ammonia
• Benzene
• Formaldehyde

• Nicotine
• Nitrosamines
• Lead
• Cadmium
• Polonium-210
• Arsenic

11 proven human carcinogens
11
LIGHT CIGARETTES

• The difference between Marlboro and Marlboro
  Lights

an extra row of ventilation holes
Image courtesy of Mayo Clinic Nicotine Dependence
Center - Research Program / Dr. Richard D. Hurt
The Marlboro and Marlboro Lights logos are
registered trademarks of Philip Morris USA.
12
NO SAFE LEVEL of SMOKING

• Smoking even 1 to 4 cigarettes a day nearly
  triples the risk of death from heart disease
• Smokers who consume fewer cigarettes can reduce
  their risk of lung cancer, but still face a much
  larger risk of premature death or disability
  compared with people who quit

Source Godtfredsen et al. (2005) JAMA, Bjartveit
et al. (2005) Tobacco Control
13
QUITTING HEALTH BENEFITS
Time Since Quit Date
Circulation improves, walking becomes easier
Lung function increases up to 30
Lung cilia regain normal function Ability to
clear lungs of mucus increases Coughing, fatigue,
shortness of breath decrease
2 weeks to 3 months
1 to 9 months
Excess risk of CHD decreases to half that of a
continuing smoker
1 year
Risk of stroke is reduced to that of people who
have never smoked
5 years
Lung cancer death rate drops to half that of a
continuing smoker Risk of cancer of mouth,
throat, esophagus, bladder, kidney, pancreas
decrease
10 years
Risk of CHD is similar to that of people who have
never smoked
after 15 years
14
YEARS of SURVIVAL GAINED RELATIVE to CONTINUED
SMOKING
Source DH Taylor et al., 2002 American Journal
of Public Health
15
WHY ADDRESS TOBACCO USE in PSYCHIATRIC
POPULATIONS?
Prevent Death Improve Health Optimize Psychiatric
Medication Effects Reduce Isolation Patient
Savings
Tobacco Industry Profits Interest
groups/politicians supported by Tobacco
Industry Tax revenues
16
TOBACCO IMPACTS PSYCHIATRIC TREATMENT

• Associated with greater AMA rates
• Hospitalized smokers twice as likely to leave
  AMA, if withdrawal not treated with nicotine
  replacement (Prochaska et al., 2004)
• Poorer outcomes among smokers with schizophrenia
• Greater psychiatric symptoms, more frequent
  hospitalizations, higher medication doses (Dalack
  Glassman, 1993 Desai et al., 2001 Ziedonis et
  al., 1994)
• Decreases some psychiatric medication levels

17
PHARMACOKINETIC DRUG INTERACTIONS with SMOKING
Drugs that may have a decreased effect due to
induction of CYP1A2

• Propanolol
• Tertiary TCAs / cyclobenzaprine (Flexaril)
• Thiothixene (Navane)
• Other medications estradiol, mexiletene,
  naproxen, phenacetin, riluzole, ropinirole,
  tacrine, theophyline, verapamil, r-warfarin (less
  active), zolmitriptan

• Caffeine
• Clozapine (Clozaril)
• Fluvoxamine (Luvox)
• Haloperidol (Haldol)
• Olanzapine (Zyprexa)
• Phenothiazines (Thorazine, Trilafon, Prolixin,
  etc.)

Smoking cessation may reverse the effect.
18
FINANCIAL IMPACT of SMOKING
Buying cigarettes every day for 50 years _at_
3.75/pack for generic or 5.25/pack for brand
name. Money banked monthly, earning 5.5 interest
2
Packs per day
1.5
1
19
ANNUAL SMOKING-ATTRIBUTABLE ECONOMIC COSTSU.S.,
19952001
Prescription drugs, 6.4 billion
Other care, 5.4 billion
Medical expenditures (1998)
Ambulatory care, 27.2 billion
Nursing home, 19.4 billion
Hospital care, 17.1 billion
Societal costs 7.65 per pack
Annual lost productivity costs (19972001)
Men, 61.9 billion
Women, 30.5 billion
Billions of dollars
CDC. MMWR 200251300303 and MMWR
200554625-628.
20
EPIDEMIOLOGY of TOBACCO USE SUMMARY

• Smoking rates are 40 to 90 in the mentally ill
  2 to 4 times that of the general population.
• Tobacco use adversely effects psychiatric
  treatment.
• Lifetime financial costs of buying cigarettes can
  exceed 1 million for a heavy smoker.
• At any age, there are major health benefits to
  quitting smoking.

21
WHY do INDIVIDUALS with MENTAL ILLNESS SMOKE?
Smoking in adolescence is associated with
psychiatric disorders in adulthood, including
panic disorder, GAD and agoraphobia, depression
and suicidal behavior, substance use disorders,
and schizophrenia (Breslau et al., 2004 Weiser
et al., 2004 Goodman, 2000 Johnson et al., 2000)
MENTAL ILLNESS
SMOKING
Active psychiatric disorders are associated with
daily smoking and progression to nicotine
dependence (Breslau et al., 2004).
22
FACTORS ASSOCIATED with TOBACCO USE in the
MENTALLY ILL
Psychological/Behavioral Conditioning effects
Coping tool Social interactions
Boredom
Biologic Pharmacologic Genetic
predisposition Alleviation of
withdrawal Pleasure effects
Weight control
Tobacco Use
Systemic Treatment Use of cigarettes for
reinforcement Failure to treat
23
NEUROCHEMICAL and RELATED EFFECTS of NICOTINE
N I C O T I N E
? Pleasure, reward ? Arousal, appetite
suppression ? Arousal, cognitive enhancement ?
Learning, memory enhancement ? Reduction of
anxiety and tension ? Reduction of anxiety and
tension ? Mood modulation, appetite suppr.

• Dopamine
• Norepinephrine
• Acetylcholine
• Glutamate
• ?-Endorphin
• GABA
• Serotonin

Benowitz. Nicotine Tobacco Research
19991(suppl)S159S163.
24
DOPAMINE REWARD PATHWAY
Prefrontal cortex
Dopamine release
Stimulation of nicotine receptors
Nucleus accumbens
Ventral tegmental area
Nicotine enters brain
Amygdala
25
acetylcholine
State of Nicotine Withdrawal
nicotine
Chronic Smoking Effects
nicotine receptor
pit
Source S.M. Stahl (2000). Essential
Psychopharmacology
26
CHRONIC ADMINISTRATION of NICOTINE EFFECTS on
the BRAIN
Perry et al. J Pharmacol Exp Ther
199928915451552.
27
GENETIC EFFECTS on NICOTINE METABOLISM
4.4
0.4
9.8
Nornicotine
Nicotine-1'- N-oxide
Nicotine
Nicotine
Nicotine glucuronide

• CYP2A6
• Aldehyde oxidase

4.2
80
Trans-3'- hydroxycotinine
Trans-3'- hydroxycotinine
Cotinine
Cotinine
13.0
33.6
Trans-3'- hydroxycotinine glucuronide
Cotinine glucuronide
12.6
Norcotinine
7.4
Cotinine- N-oxide
2.0
Reprinted with permission, Benowitz et al., 1994.
2.4
28
Source S.M. Stahl (2000). Essential
Psychopharmacology
29
Source S.M. Stahl (2000). Essential
Psychopharmacology
30
NICOTINE ADDICTION CYCLE
Reprinted with permission. Benowitz. Med Clin N
Am 19922415437.
31
NICOTINE WITHDRAWAL EFFECTS

• Dysphoric or depressed mood
• Insomnia and fatigue
• Irritability/frustration/anger
• Anxiety or nervousness
• Difficulty concentrating
• Impaired task performance
• Increased appetite/weight gain
• Restlessness and impatience
• Cravings

Most symptoms peak 2448 hr after quitting and
subside within 24 weeks.
American Psychiatric Association. (1994). DSM-IV.
Hughes et al. (1991). Arch Gen Psychiatry
485259. Hughes Hatsukami. (1998). Tob Control
79293.
Not considered a withdrawal symptom by DSM-IV
criteria.
32
WHAT is ADDICTION?

• Compulsive drug use, without medical purpose, in
  the face of negative consequences
• Alan I. Leshner, Ph.D.
• Former Director, National Institute on Drug Abuse
• National Institutes of Health

33
MODEL of ADDICTION
Positive Reinforcement
Impulse control disorders
tension / arousal
regret / guilt / self-reproach
impulsive acts
TIME
Pleasure / relief / gratification
Compulsive disorders
anxiety / stress
obsessions
repetitive behaviors
relief of anxiety / relief of stress
Negative Reinforcement
Source GF Koob et al. (2004) Neuroscience and
Biobehavioral Reviews
34
DSM-IV TOBACCO USE DISORDERS

• Nicotine Withdrawal
• Daily use of nicotine
• Abrupt cessation/reduction followed within 24 hrs
  by 4
• Depressed mood
• Insomnia
• Irritability
• Anxiety
• Difficulty concentrating
• Decreased HR
• Increased appetite
• Clinically significant impairment
• Not due to GMC

• Nicotine Dependence
• Maladaptive pattern of use with significant
  impairment manifested by 3 in 12-mos
• Tolerance
• Withdrawal
• ? Use
• Unsuccessful efforts to stop
• Time investment
• Loss of important activities
• Continued use despite knowledge of physical or
  psychological problems

35
PSYCHIATRISTS in PRACTICE (Himelhoch Daumit,
2003)

• 1992-96 Natl Ambulatory Medical Care Survey
• 23 of psychiatric visits dropped from analysis
  because patient smoking status unknown
• For patients identified as smokers (N1610)
• Cessation counseling offered at 12 of visits
• Nicotine Dependence not diagnosed at any visit
• NRT never prescribed

36
PSYCHIATRY RESIDENTS (N105) ENGAGEMENT in the
5-As
Source Prochaska, Fromont et al., 2005 Acad
Psychiatry
37
TOBBACO USE SUMMARY

• Tobacco products are effective delivery systems
  for the highly addictive drug nicotine.
• Nicotine activates the dopamine reward pathway in
  the brain, which reinforces continued tobacco
  use.
• Nicotine dependence and withdrawal are DSM-IV
  psychiatric disorders.
• Tobacco dependence involves biological,
  psychological, and social factors requiring a
  long-term multifaceted treatment approach.

38
Treating Tobacco Dependence Motivational
Behavioral Models
39
TOBACCO DEPENDENCEA 2-PART PROBLEM
Tobacco Dependence
Physiological
Behavioral
Treatment should address the physiological and
the behavioral aspects of dependence.
40
TREATING NICOTINE DEPENDENCE
In terms of lives saved, quality of life, and
cost-efficacy, treating smoking is considered the
most important activity a clinician can do.
-- John Hughes, MD Professor of
Psychiatry University of Vermont
41
TOBACCO TREATMENT GUIDELINES

• All patients ought to be screened for tobacco
  use, advised to quit, and offered intervention
• All patients should be offered pharmacological
  treatment for quitting smoking, unless
  contraindicated
• There is a dose response relationship with the
  amount of contact provided

American Psychiatric Association, 1996 U.S.
Public Health Service, 2000
42
CLINICIAN INTERVENTIONS
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
43
DOSE RESPONSE RELATIONSHIP of FOLLOW UP CARE
5 months (or more) postcessation
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
44
WHY MENTAL HEALTH PROVIDERS?

• Often the clinician for whom contact is the most
  frequent and who knows the patient best
• Ability to combine psychopharmacological and
  behavioral/counseling treatment
• Trained in substance abuse treatment
• Able to identify and address any changes in
  psychiatric symptoms during the quit attempt

45
NATIONAL CANCER INSTITUTESFIVE As for TREATING
TOBACCO
46
The FIVE As ASK

• Never
• Former
• Current

Tobacco use is included in the intake assessment
and needs to be documented for every patient.
47
The FIVE As ADVISE
48
The FIVE As ASSESS
49
STUDIES of PSYCHIATRIC PATIENTS READINESS to
QUIT
Smokers with mental illness are just as ready to
quit smoking as the general population of smokers.

• No relationship between psychiatric symptom
  severity and readiness to quit

50
ASSIST TAILOR TREATMENT to PATIENTS READINESS
to QUIT
Does the patient now use tobacco?
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
51
ASSIST Not Ready to QUIT
Not thinking about quitting in the next month

• May not be aware of the need to quit
• Struggling with ambivalence about change
• Not ready to change, yet
• Pros of tobacco use outweigh the cons
• May have been advised to forgo quitting
• May have had bad prior experiences with quitting

GOAL Start thinking about quitting
52
STRATEGIES for PATIENTS NOT READY TO QUIT

• DOs
• Demonstrate empathy, foster
  communication
• Ask noninvasive and open-ended questions
  identify reasons for tobacco use
• Conceptualize tobacco use as a self-destructive
  behavior
• Raise awareness of pros and decrease emphasis on
  cons of quitting
• Advise to quit and provide information
• Leave decision up to patient

• DONTs
• Persuade
• Cheerlead
• Tell patient how bad tobacco is in a judgmental
  manner
• Be confrontational
• Provide a treatment plan
• Rx meds to quit

53
RAISING AWARENESS TOBACCO USE MOOD LOG

• Use the Mood Log to raise patients awareness of
  their tobacco use
• For each day, patient should record of
  cigarettes smoked, of pleasant activities, and
  provide a mood rating.
• Review log sheets with patient to identify
  relationship between smoking, activities /
  isolation, and mood

Is patients tobacco use associated with
isolation and poorer mood?
54
SUMMARY PATIENTS NOT yet READY to QUIT

• Clinician goals include
• Building rapport
• Planting a seed to move patient forward
• Opening a door to facilitate further counseling
• Helping patients become more aware of their
  smoking behavior
• Providing education and establishing yourself as
  a resource

55
CASE 1 Vera

• 48 year old divorced woman
• Dual diagnosis treatment facility
• Bipolar disorder, alcohol dependence, h/o crack
  cocaine dependence
• Smokes 1.5 packs/day, not intending to quit
• Ill likely die with a cigarette in my mouth

56
ASSIST TAILOR TREATMENT to PATIENTS READINESS
to QUIT
Does the patient now use tobacco?
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
57
ASSIST Ready to Quit
READY TO QUIT in NEXT 30 DAYS

• Patients are aware of the need to, and the
  benefits of, making the behavioral change
• Getting ready to take action

GOAL Achieve cessation
58
STRATEGIES for PATIENTS READY to QUIT

• Key Questions to Ask
• Why do you want to quit now?
• How confident are you that youll be able to
  quit?
• Have you quit in the past? What worked for you
  then?
• What are key triggers for you with smoking?
• How do stress and your mood play into your
  smoking?
• Who can support you with quitting?
• What concerns do you have about quitting?
  (withdrawal symptoms, weight gain, coping with
  stress)
• How can we work together to manage your anxiety
  (or other psychiatric symptoms) during the
  quitting process?

59
STRATEGIES for PATIENTS READY to QUIT

• DOs
• Discuss and develop coping strategies
• Offer pharmacological treatment, unless
  contraindicated
• Set a quit date!
• Schedule follow up visit

60
COPING with QUITTING

• Cognitive strategies
• Review of commitment to quitting
• Distractive thinking
• Positive self-talks
• Relaxation through imagery
• Mental rehearsal and visualization

61
COPING with QUITTING (contd)

• Examples
• Thinking about cigarettes doesnt mean you have
  to smoke one.
• Thinking about something doesnt mean you have
  to do it.
• Tell yourself Its just a thought, or I am in
  control.
• Say the word STOP! out loud, or visualize a stop
  sign.
• When you have a craving, remind yourself that
• The urge for a cigarette will only go away if I
  dont smoke.
• As soon as you get up in the morning, look in the
  mirror and say to yourself
• I am proud that I made it through another day
  without smoking.

62
COPING with QUITTING (contd)

• Behavioral strategies
• Control your environment
• Smoke-free home and workplace
• Alter or remove cues to tobacco use
• Modify behaviors that you associate with tobacco
  when, what, where, how, with whom
• Actively avoid trigger situations
• Substitutes for smoking
• Water, chewing gum or hard candies (oral
  substitute)
• Take a walk, diaphragmatic breathing,
  self-massage
• Rely on social support
• Actively work to alleviate withdrawal symptoms

63
STRESS MANAGEMENT
The Facts
The Myths

• Smoking gets rid of all my stress
• I cant relax without a cigarette

• There will always be stress in ones life
• There are many ways to relax without a cigarette

Smokers confuse the relief of withdrawal with the
feeling of relaxation
STRESS MANAGEMENT SUGGESTIONS Deep breathing,
shifting focus, taking a break
64
SOCIAL SUPPORT for QUITTING

• Key ingredients for successful quitting
• Social support as part of treatment
  (intra-treatment)
• Social support outside of treatment
  (extra-treatment)

• PATIENTS SHOULD BE ADVISED TO
• Ask family, friends, and coworkers for support
  ask them not to smoke around you and not to leave
  cigarettes out
• Get individual, group, or telephone counseling

Patients who receive social support and
encouragement are more successful in quitting
65
The FIVE As ARRANGE

• Arrange follow-up care
• Follow-up in person or via phone within 1 to 3
  days after quit attempt
• Congratulate success
• Address lapses let a slip slide
• Assess pharmacotherapy use and problems

ARRANGE
66
CASE 2 Mr. Brooks

• 58 year old divorced male, unemployed
• PTSD clinic at Veterans Hospital
• PTSD, h/o polysubstance abuse, chronic pain
• Smokes 1.5 packs per day
• Interested in quitting

67
ASSIST TAILOR TREATMENT to PATIENTS READINESS
to QUIT
Does the patient now use tobacco?
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
68
ASSIST RECENT QUITTER
ACTIVELY TRYING to QUIT for GOOD

• Patients have quit using tobacco sometime in the
  past 6 months and are taking steps to increase
  their success
• Withdrawal symptoms occur
• At high risk for relapse

GOAL Remain tobacco-free for at least 6 months
69
STRATEGIES for RECENT QUITTERS

• DOs
• Praise progress - solicit commitment to quit for
  good
• Evaluate current quit attempt
• Status of attempt
• Slips or relapse
• Medication use, plans for discontinuation
• Ask about social support
• Identify temptations and triggers for relapse
• Negative affect, smokers, eating, alcohol,
  cravings, stress
• Encourage healthful alternative behaviors to
  replace tobacco use
• Offer tips for relapse prevention

70
RELAPSE PREVENTION for RECENT LONG-TERM QUITTERS

• Goal To support lasting changes in thoughts and
  behaviors around quitting smoking
• Congratulate success!
• Highlight continued benefits of abstinence
• Identify ongoing sources of social support
• Assess prolonged withdrawal symptoms
• Add or combine pharmacotherapy agents or extend
  use of pharmacotherapy
• Address reduced motivation or feelings of
  deprivation
• Reassure these feelings are common and will pass
  with time
• Encourage engagement in rewarding activities
• Probe for lapses

71
ADDRESSING CONCERNS about POSTCESSATION WEIGHT
GAIN

• Most quitters gain weight
• Most gain lt 10 pounds, but there is a wide range
• Discourage strict dieting while quitting
• Recommend physical activity (e.g., walking,
  biking)
• Encourage a healthy diet, planned meals,
  high-fiber foods
• Increase water intake
• Chew sugarless gum
• Select nonfood rewards
• Maintain patient on pharmacotherapy shown to
  delay weight gain
• Refer patient to a specialist or program

72
CASE 3 William

• 34 year old HIV gay male
• HIV/AIDS Community Health Center
• Depression with heavy alcohol use
• Smoked 15 cigarettes/day for 18 years
• Quit 3 weeks ago, smoked 2 cigarettes last night
• Frustrated by weight gain, cravings, and poor mood

73
ASSIST TAILOR TREATMENT to PATIENTS READINESS
to QUIT
Does the patient now use tobacco?
Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
74
READINESS TO QUIT A REVIEW
Quit date
- 30 days
6 months
Recent quitter
Not ready to quit
Former tobacco user
PROMOTE MOTIVATION
BEHAVIORAL COUNSELING
RELAPSE PREVENTION
Ready to quit
BEHAVIORAL COUNSELING PHARMACOTHERAPY
75
CESSATION COUNSELING SUMMARY

• Routinely identify tobacco users (ASK)
• Strongly ADVISE patients to quit
• ASSESS stage at each contact
• Tailor intervention messages (ASSIST)
• Be a good listener
• Minimal intervention in absence of time for more
  intensive intervention
• ARRANGE follow-up
• Use the referral process, if needed

76
INTEGRATING TOBACCO TREATMENT into PSYCHOTHERAPY

• Quotes from Psychodynamically Trained UCSF
  Faculty
• Attention to substance abuse is part of
  psychotherapy and how we address self-defeating,
  self-destructive behaviors and examine resistance
  to change and support change.
• Ideally, link to the central pathology When
  people are depressed they dont take very good
  care of themselves. I want to help you take as
  good care of yourself as possible.
• If the patient says he needs to smoke to deal
  with psychiatric symptoms I would respond, Wow,
  you must have a lot of stress and anxiety if you
  need to take a cancer-causing agent to deal with
  it. I think we really need to look at your level
  of stress. It should be a real priority.

77
Treating Tobacco Dependence Pharmacological
Treatments
78
PHARMACOTHERAPY

• All patients attempting to quit should be
  encouraged to use effective pharmacotherapies for
  cessation except in the presence of special
  circumstances.

Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
79
PHARMACOLOGIC METHODS

• First-Line (FDA Approved)
• Nicotine Replacement Therapy (NRT)
• Bupropion (Zyban)
• Varenicline (Chantix)
• Second-line (evidence-based but not FDA approved)
• Nortriptyline
• Clonidine

80
FDA APPROVALS SMOKING CESSATION
Drugs in Development rimonabant, nicotine
vaccine, etc.
200X
2006
OTC nicotine gum patchRx nicotine nasal spray
2002
Rx transdermal nicotine patch
Rx varenicline
1997
Rx nicotine gum
1996
OTC nicotine lozenge
1991
Rx nicotine inhaler Rx bupropion SR
1984
81
PLASMA NICOTINE CONCENTRATIONS for
NICOTINE-CONTAINING PRODUCTS
Cigarette
Moist snuff
0 10 20
30 40
50 60
Time (minutes)
82
TRANSDERMAL NICOTINE PATCH

• ADVANTAGES
• Provides consistent nicotine levels
• Easy to use and conceal
• Fewer compliance issues

• DISADVANTAGES
• Patients cannot titrate the dose
• Allergic reactions to adhesive may occur
• Taking patch off to sleep may lead to morning
  nicotine cravings

83
PATIENT EDUCATION Nicotine Patch

• Apply patch to hairless area -- new location
  daily
• Water will not harm the nicotine patch if it is
  applied correctly patients may bathe, swim,
  shower, or exercise while wearing the patch
• Do not cut patches to adjust dose
• Nicotine may evaporate from cut edges
• Patch may be less effective
• Keep new and used patches out of the reach of
  children and pets

84
NICOTINE GUM LOZENGE

• DISADVANTAGES
• Gastrointestinal side effects may be bothersome
• Gum may be socially unacceptable and difficult to
  use with dentures
• Patients must use proper chewing technique to
  minimize adverse effects

• ADVANTAGES
• Patients can titrate therapy to manage withdrawal
  symptoms
• May satisfy oral cravings
• May delay weight gain

85
PATIENT EDUCATION Nicotine Gum Lozenge

• Chew and park gum
• To improve chances of quitting, use at least nine
  pieces of the gum or lozenge daily
• The effectiveness of nicotine gum and lozenge may
  be reduced by some foods and beverages
• ? Coffee ? Juices
• ? Wine ? Soft drinks

Do NOT eat or drink for 15 minutes BEFORE or
while using nicotine gum or lozenge.
86
NICOTINE INHALER

• ADVANTAGES
• Patients can easily titrate therapy to manage
  withdrawal symptoms.
• The inhaler mimics hand-to-mouth ritual of
  smoking.

• DISADVANTAGES
• Initial throat or mouth irritation can be
  bothersome.
• Cartridges should not be stored in very warm
  conditions or used in very cold conditions.
• Patients with underlying bronchospastic disease
  must use the inhaler with caution.

87
NICOTINE NASAL SPRAY

• DISADVANTAGES
• Nasal/throat irritation may be bothersome
• Dependence can result
• Patients must wait 5 min before driving or
  operating heavy machinery

• ADVANTAGES
• Most rapidly absorbed form of nicotine
  replacement
• Patients can easily titrate therapy to rapidly
  manage withdrawal symptoms
• Demonstrated use with smokers with schizophrenia

88
COMBINATION NRT

• Long-acting formulation (patch)
• Produces relatively constant levels of nicotine
• PLUS
• Short-acting formulation (gum, lozenge, inhaler,
  nasal spray)
• Allows for acute dose titration as needed for
  withdrawal symptoms

Reserve for patients unable to quit using
monotherapy
89
BUPROPION SR

• DISADVANTAGES
• Should be avoided in patients with an increased
  risk for seizures
• Side effect profile
• Common dry mouth, anxiety, insomnia (avoid
  bedtime dosing)
• Less Common tremor, skin rash

• ADVANTAGES
• Easy to use
• Can be used with NRT
• May be beneficial in patients with depression

90
BUPROPIONMECHANISM OF ACTION

• Atypical antidepressant thought to affect levels
  of various brain neurotransmitters
• Dopamine
• Norepinephrine
• Clinical effects
• ? craving for cigarettes
• ? symptoms of nicotine withdrawal

91
VARENICLINE

• DISADVANTAGES
• Common side effects
• Nausea (in up to 33 of pts)
• Sleep disturbances (insomnia, abnormal dreams)
• Constipation
• Flatulence
• Vomiting

• ADVANTAGES
• Oral formulation with twice-a-day dosing
• Offers a new mechanism of action for persons who
  previously failed using other medications
• Early industry-sponsored trials suggest this
  agent is superior to bupropion SR

92
VARENICLINEMECHANISM of ACTION

• Binds with high affinity and selectivity at ?4?2
  neuronal nicotinic acetylcholine receptors
• Stimulates low-level agonist activity
• Competitively inhibits binding of nicotine
• Clinical effects
• ? symptoms of nicotine withdrawal
• Blocks dopaminergic stimulation responsible for
  reinforcement reward associated with smoking

93
VARENICLINEPHARMACOKINETICS

• Absorption Virtually complete after oral
  administration not affected by food
• Metabolism Undergoes minimal hepatic metabolism
• Elimination Primarily renal through glomerular
  filtration and active tubular secretion 92
  excreted unchanged in urine
• Half-life 24 hours

94
VARENICLINE DOSING
Patients should begin therapy 1 week PRIOR to
their quit date. The dose is gradually increased
to minimize treatment-related nausea and insomnia.
Initial dose titration
95
LONG-TERM (?6 month) QUIT RATES for AVAILABLE
CESSATION MEDICATIONS
23.9
22.5
20.0
19.5
17.1
16.4
14.6
Percent quit
11.5
11.8
10.2
9.4
9.1
8.8
8.6
Data adapted from Silagy et al. (2004). Cochrane
Database Syst Rev Hughes et al., (2004).
Cochrane Database Syst Rev. Gonzales et al.,
(2006). JAMA and Jorenby et al., (2006). JAMA
96
COMBINATION THERAPY PATCH PLUS BUPROPION SR
Percentage of patients quit at 12 months after
treatment


Odds Ratio
plt.001 compared with placebo
Jorenby et al. N Engl J Med 1999340(9)685691.
97
NORTRIPTYLINE (second-line)

• DISADVANTAGES
• Seizure risk is increased as in all
  antidepressants
• May require blood level monitoring and EKG
• Dangerous in overdose
• Side-effect profile
• Dry mouth, orthostatic hypotension, cardiac
  arythmia, constipation, urinary retention, sexual
  dysfunction, sedation, etc.

• ADVANTAGES
• Effective treatment for smoking cessation and
  depression
• Can combine with NRT
• Useful in patients with chronic pain, insomnia,
  and anxiety
• Inexpensive
• One of the best tolerated TCAs

98
NORTRIPTYLINE DOSING for SMOKING CESSATION

• Begin treatment 4 weeks prior to quit date at 25
  mg q HS
• Increase as tolerated by 25 mg per week up to 75
  100 mg to reach therapeutic blood levels of 50
  150 ng/ml
• Continue for 7 weeks with a 1-week taper (12
  weeks total)

Source Hughes, Stead Lancaster (2005). NTR
99
CLONIDINE (second-line)

• DISADVANTAGES
• Fewer efficacy studies
• Medication interactions
• Side-effect profile
• Decreased HR, sedation, orthostatic hypotension,
  dizziness, dry mouth

• ADVANTAGES
• Inexpensive
• Good for patients who are anxious or have
  insomnia
• Consider for patients with contraindications to
  antidepressants
• Consider for patients with hypertension
• Second-line treatment for ADHD and opioid
  withdrawal

100
CLONIDINE DOSING for SMOKING CESSATION

• Usually in the range of 0.1 0.4 mg/day in
  divided TID or QID or 0.2 mg patch (TTS-2) q week
• Some patients may require more
• Initiate clonidine therapy 48 to 72 hours before
  quit attempt

Source Gourlay, Stead, Benowitz. (2005).
Cochrane Reviews
101
COMPARATIVE DAILY COSTS of PHARMACOTHERAPY
6.07
5.88
3.75 generic
5.00 in CA
4.00
3.67
3.48 (generic)
2.84 (generic)
2.62 (generic)
1.13 (generic)
.91 (generic)
Cost per day, in U.S. dollars
102
EMERGING TECHNOLOGIES

• Rimonabant
• Approved obesity treatment in European Union
• FDA approval for obesity expected in late 2006
• FDA non-approval for smoking cessation
• Nicotine Vaccine
• 3 companies in development (Japanese, US, Swiss)
• NicVAX (Nabi) and NicQb (Cytos AG) in Phase II
  Trials
• Goal to prevent relapses after quitting

103
CASE 4 Ms. Allen

• 34 year old married woman, employed
• Intake at outpatient mental health clinic
• Dysthymia history of eating disorder
• Smokes 10 cigarettes per day
• Wants to quit, recently failed with NRT gum

104
Treating Special Populations
105
TOBACCO USE in PREGNANCY

• Health complications to the fetus
• Low birth weight
• Breakthrough bleeding
• Miscarriage / death of the fetus
• Placenta previa
• Abrubtio placenta
• Premature rupture of membranes
• Premature birth
• Fetal blood holds onto CO more strongly than
  oxygen leading to growth retardation and
  asphyxiation

106
TREATING thePREGNANT SMOKER

• Comprehensive psychosocial and behavioral
  intervention that includes pregnancy-specific
  materials
• Pregnancy Toll-free Quitline 1-866-66-START
• If pt unable to quit without pharmacological
  treatment, NRT may be prescribed at any point in
  the pregnancy.
• Bupropion and varenicline currently not
  recommended (Category C drugs). Use only if
  clearly indicated.

Fiore et al. Treating Tobacco Use and Dependence.
Clinical Practice Guideline. Rockville, MD
USDHHS, PHS, 2000.
107
AFTER DELIVERY

• Relapse prevention is critical. Nonsmoking in
  the mother (and father) important for avoiding
  infant exposure to secondhand smoke to prevent
  SIDs and childhood asthma.
• Promote breastfeeding in all cases, even for
  mothers who smoke or use NRT.
• Bupropion and varenicline not currently
  recommended for smoking cessation with
  breastfeeding women.

Source Melvin Gaffney, 2004 Nicotine Tobacco
Research
108
CASE 5 Tammy

• 18 year old single pregnant woman
• County-funded womens care clinic
• ADHD and borderline intellectual functioning
• Reduced smoking from 30 to 5 cigarettes/day
• Wants to quit but feels cannot reduce further

109
SMOKING and SUBSTANCE USE

• Tobacco-related diseases account for 50 of
  deaths among individuals treated for alcohol
  dependence (Hurt et al., 1996)
• Death rate 4-xs greater for cigarette smoking vs.
  nonsmoking long-term drug abusers (Hser, 1994)
• Health consequences of tobacco and other drug use
  synergistic 50 greater than sum of each
  individually (Bien Burge, 1990)

110
A META-ANALYSIS of SMOKING CESSATION
INTERVENTIONS with INDIVIDUALS in SUBSTANCE ABUSE
TREATMENT or RECOVERY

• Judith Prochaska, PhD, MPH
• Kevin Delucchi, PhD Sharon Hall, PhD
• University of California, San Francisco
• Supported by TRDRP 11FT-0013 and NIDA P50
  DA09253
• JCCP 2004

111
OVERALL SMOKING CESSATION RATES
PostTreatment Long-term FU
18 studies
15 studies
112
DRUG ALCOHOL ABSTINENCE RATES among
PARTICIPANTS IN TREATMENT
9 studies
7 studies
113
TREATING SMOKERS with SUBSTANCE USE DISORDERS

• Significant treatment effects for quitting
  smoking at post-treatment, but not at long-term
  follow up (gt 6 months)
• At long-term follow up, evidence of improved
  sobriety among intervention participants
• 25 greater odds of being sober if exposed to the
  tobacco cessation intervention

Source Prochaska et al., 2004. JCCP.
Meta-analysis
114
TREATMENT of DEPRESSED PSYCHIATRIC OUTPATIENTS
for CIGARETTE SMOKING

• Sharon Hall, PhD, Janice Tsoh, PhD, Judith
  Prochaska, PhD, MPH, Stuart Eisendrath, MD,
  Joseph Rossi, PhD, Colleen Redding, PhD,
• Amy Rosen, PsyD, Marc Meisner, MD, Gary Humfleet,
  PhD, Julie Gorecki, MA
• University of California, San Francisco
• Supported by NIDA P50 DA09253

115
STUDY DESIGN

• 322 depressed smokers recruited from four
  outpatient psychiatry clinics
• Stepped Care Intervention
• Stage-based expert system counseling
• Nicotine patch
• 6 session individual CBT counseling
• Bupropion available
• Brief Contact Control
• Primary outcome
• 7 day PPA _at_ 12 18 months, CO verified

116
ABSTINENCE RATES by TREATMENT CONDITION
117
MENTAL HEALTH OUTCOMES

• Among depressed smokers who quit
• No increase in suicidality
• Quit 0 vs Smoking 1-4
• No increase in psych hospitalization
• Quit 0-1 vs. Smoking 2-3
• Comparable improvements in BDI and STAXI scores
  and of days with emotional problems

118
BDI TOTAL SCORE
Moderate
Mild
Minimal
119
TREATING DEPRESSED SMOKERS

• Stage-based tobacco treatment with CBT and NRT
  significant effects at 12 and 18 months
• No evidence of worsened psychiatric symptoms
  associated with quitting smoking
• Smoking can be treated concurrent with depression
  without adverse effects to mental health
  functioning

120
TREATING SMOKERS with SCHIZOPHRENIA

• Treatments tailored for smokers with
  schizophrenia no more effective than standard
  cessation programs (George et al., 2000)
• Atypical antipsychotics (clozapine) associated
  with greater cessation than typicals
• Tobacco abstinence (1-wk) not associated with
• Worsening of attention, verbal learning/memory,
  working memory, or executive function/inhibition
  nor worsening of clinical symptoms in individuals
  with schizophrenia (Evins et al., 2005)

121
CASE 6 Mr. Lee

• 75 year old man, board and care
• City clinic monthly med management
• Schizoaffective disorder, depressed type
• Smokes 2 packs/day
• Believes he must smoke to breathe

122
ADOLESCENTS TOBACCO USE

• 23 of US high school students report tobacco use
  in the past month and 14 report smoking daily
• Smoking rates are even higher among adolescents
  with psychiatric disorders such as ADHD,
  depression, CD, and alcohol and illicit drug
  dependencies.
• 80 report tobacco use in the past month
• 77 report daily smoking
• 63 smoke 10 cigarettes per day
• Myers Brown, 1994, Arria et al., 1995,
  McDonald et al., 2000, Myers Macpherson, 2004

123
TREATMENT APPROACHES

• 48 published RCT with adolescents (Sussman, 2006)
• No unequivocal successes
• Promising Approaches
• Stage-based treatments
• Cognitive behavioral strategies
• Multicomponent treatments
• Nicotine patch well tolerated, safe, and rarely
  abused among adolescents (Hyland, 2005 Killen,
  2004)

124
CASE 7 Doug

• 17 year old male, lives with parents
• Hospitalized on psychiatric unit
• Explosive mood with paranoid delusions
• Smokes 1 pack per day
• Interested in staying quit when discharged

125
SUMMARY TOBACCO TREATMENTS with DEMONSTRATED
EFFICACY

• Clinician advice and counseling
• NRT, bupropion, varenicline, nortriptyline,
  clonidine
• Telephone counseling
• 1-800-QUIT-NOW (national toll-free quit line)
• www.quitline.com
• Group programs
• Aversion therapy
• Hypnotherapy

126
Efficacy and Average Sample Size of Tobacco
Cessation Studies Reviewed by the Cochrane
Library
n indicates number of studies CI. Confidence
interval. Based on Silagy et al. (2004) and
Stead et al. (2204). The Cochrane Library.
127
TOBACCO TREATMENTS LACKING EVIDENCE of EFFICACY

• SSRIs and SNRI
• Anxiolytics
• Sedative, hypnotics, buspirone
• Homeopathic treatments
• Herbal supplements

• Lobeline
• Massage Therapy
• Acupuncture
• Nicotine Anonymous

128
SET REALISTIC EXPECTATIONS

• Its a learning process. Reframe success!
• Most people make multiple quit attempts before
  they are successful.
• Longer prior quit attempts predict future success.