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Addressing Co-Occurring Schizophrenia and Nicotine Dependence


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Title: Addressing Co-Occurring Schizophrenia and Nicotine Dependence

Addressing Co-Occurring Schizophrenia and
Nicotine Dependence
  • Douglas Ziedonis, M.D., MPH
  • Department of Psychiatry,
  • Robert Wood Johnson Medical School UMDNJ
  • UMDNJ School of Public Health
  • Rutgers University Center of Alcohol Studies

Schizophrenia and Nicotine Dependence
  • Most common co-occurring addiction
    schizophrenia subtype (dual diagnosis)
  • High smoking rates due to patient system issues
  • Accounts for a BIG increase in medical illnesses
    mortality rates in this population
  • Tobacco effects medication levels effectiveness
  • Nicotine may have some beneficial aspects, but
    can be delivered without tobacco
  • Treatment Works patients are grateful for the
  • Medications Behavioral therapy are effective
  • Also need Program System changes culture,
    policy enforcement, training, funding, and
    staff training

The time is now to begin addressing tobacco in
Mental Health Settings
  • Remember when
  • Drug versus Alcohol Treatment Programs
  • Mental Health versus Addiction Treatment Programs
  • SAMHSAs definition of co-occurring disorders
  • Model MH programs are better addressing tobacco
  • NIDA is funding new research initiatives for
    Schizophrenia and Nicotine Dependence
  • Recent Robert Wood Johnson Foundation Initiative
  • UMDNJ State-Wide Program
  • July 2003 issue of Psychiatric Annals

Addressing Tobacco in Addiction and Mental Health
  • 44 of all cigarettes consumed in the US are by
    individuals with a current mental disorder
  • 256 Billion Dollars on Cigarettes
  • Estimates of about 2 billion spent by smokers
    with schizophrenia on cigarettes annually
  • 75 of individuals with either a mental disorder
    (addiction or mental illness) smoke cigarettes
  • Most smoke and die due to smoking caused diseases
  • Nicotine use is a trigger for other substance use

Unique Features of Schizophrenia
  • Schizophrenia about 1 of the population
  • developmental brain disorder
  • stress gene / environment vulnerabilities
  • heterogeneous population (onset, course,
    symptoms, end state)
  • positive negative symptoms
  • cognitive limitations and aberrant sensory
  • Low Motivation
  • Low Self-Efficacy
  • Limited Interpersonal Skills therapeutic
  • More Cravings during Withdrawal
  • Cocaine dependence (Smelson et al, 2002)

Schizophrenia and Tobacco
  • 70-90 are tobacco dependent (setting specific)
  • 50 of the smokers are heavy smokers
  • Heavy smoking associated with
  • Increased positive symptoms and decreased
    negative symptoms
  • More other substance use disorders
  • More frequent psychiatric hospitalizations
  • Fewer parkinsonian EPS medication side-effects
  • Increased suicide risk
  • Polydipsia

Schizophrenia and Tobacco
  • Effective and efficient smokers
  • high CO cotinine levels
  • Many low motivated to quit
  • but growing interest to seek help
  • Most first episode schizophrenics already smoke
  • PH efforts today have not helped this population
  • Tobacco alters medication blood levels

Tobacco Smoking Effects Some Psychiatric
Medication Blood Levels
  • Smoking induces the P450s 1A2 isoenzyme
    secondary to the polynuclear aromatic
  • Smoking increases the metabolism of some
  • Haldol, Prolixin, Olanzapine, Clozapine,
    Mellaril, Thorazine, etc
  • Caffeine is metabolized through 1A2
  • CHECK for medication SE or relapse to mental
    illness with changes in smoking status
  • Nicotine does not change medication blood levels
  • NRT doesnt effect medication blood levels
  • Nicotine may modulate cognition, psychiatric
    symptoms, and medication side effects

Are patients better off smoking?
  • Nicotine modulates both dopamine and glutamate
  • Nicotinic acetylcholine receptors on dopamine
  • Stimulates glutamate neurons in prefrontal cortex
  • Schizophrenia gene defect low alpha 7 Nic
  • Nicotine transiently improves attention and
    sensory gating and reduces number of leading
    saccades during smooth pursuit eye movement.
  • MAO type B inhibition by tobacco smoke components
    also induces dopamine transmission
  • Smoking may enhance visuospatial working memory
    in this population (George et al, 2002)

Nicotine may help Schizophrenia
  • If nicotine helps schizophrenia assess benefits
    of providing Nicotine replacement (NRT) alone
    without Tobacco
  • Belief quitting smoking worsens schizophrenia?
    Whats the evidence?
  • Worse withdrawal?

Reduced life expectancy
  • 20 shorter life span in schizophrenia versus the
    general population
  • Tobacco caused diseases that also lead to death
    are more prominent in schizophrenia than the
    general population
  • Higher standardized mortality rates than general
    pop for
  • Cardiovascular disease 2.3x
  • Respiratory disease 3.2x
  • -Brown et al., 2000 Br J Psychiatry

(No Transcript)
Steinberg, M. L., Williams, J. M., Ziedonis, D.
M. (2004). Financial Implications of Cigarette
Smoking Among Individuals With Schizophrenia.
Tobacco Control, 13(2).
Tobacco use increases alcohol and other drug use
intake and cravings
  • Tobacco Craving Laboratory with schizophrenic
  • Animal and human laboratory research on effect of
    tobacco use on increasing consumption and
  • Tobacco use correlates in dose-dependent fashion
    with cocaine and heroin use
  • Frosch, Shoptaw, Nahom, Jarvik, Exptl Clin
    Psychopharm. 2000 897-103

Why the high rates of nicotine dependence among
these groups ?
  • Biological / Genetic
  • Psychological (Self-Medication?)
  • Social / Environmental / Cultural
  • Institutional / MH System Factors

Hypotheses for initiation, maintenance, and
difficulty quitting
  • Increased propensity to dependence?
  • Illness modulation effect?
  • Side effect reduction?
  • Immediate
  • self-medicating
  • effect?
  • Social factors?

Biological Factors
  • Brain Reward Systems Mesolimbic Dopamine system
  • Ventral Tegmental Area (VTA)
  • Nucleus Accumbens (NAc)
  • Projections to Medial Prefrontal Cortex
  • Genetics
  • Tryptophan Depletion study increases smoking
    intensity but not negative symptoms or depression

(No Transcript)
Acetylcholine hypothesis of Schizophrenia
  • A malfunction in interneuronal function involving
    Acetylcholine transmission may be a core
    abnormality in schizophrenia
  • alpha- 7 nicotinic receptor malfunction
  • Alpha 7 receptor ligand gated Ca ion channel
  • Function effects attention, memory and cognitive
  • This receptor is involved in the sensory gating
    deficit (abnormal P50 auditory-evoked potential)
  • (R. Freedman, U of Colorado)

Psychological Factors
  • Low self-efficacy
  • Poor coping
  • Poor compliance
  • Low motivation
  • Fear of worsening symptoms
  • Patients perceive tobacco helps them reduce
    anxiety, boredom, and idle time
  • May perceive the reinforcement value of cigarette
    smoking as being stronger than non-psychiatric
    patients and feel they would require more
    incentives to quit (Spring et al, 2003)

Social Factors
  • Cultural differences
  • Japanese patients with schizophrenia tobacco
    dependence at 34 similar to the general
  • Taiwan 40 smokers India 38 (lack of economic
    independence and family restrictions may account)
  • Family support restrictions
  • Few non-smoking social supports
  • Live with other smokers - Group home smoking
  • Smoking within the mental health settings
  • Smoking as behavioral reinforcer by staff
  • Smoking as a normalizing behavior - substance
    users are perceived as friends

Stigma vs Schizophrenia
  • other than increase morbidity and mortality why
    should we address tobacco for those patients?
  • Staff are upset when they hear of small towns
    with smoking rates of 80 in some states but not
    within mental health settings
  • what else will they be able to do in their free
  • Interestingly, patients have reported feeling
    less stigmatized when they smoke (promote sense
    of freedom).

Institutional Barriers to Tobacco Dependence
  • Lack of staff training
  • not my role go to primary care
  • Staff fear that patients will misuse NRT or smoke
    while taking NRT
  • Staff who smoke normalize smoking, staff may
    help patients access cigarettes, program may sell
  • Restrictive formulary or insurance coverage of
    the cost of medications
  • Limited income and cannot afford OTC medications

Under-Diagnosis Under-Treatment
  • Nicotine dependence documented in 2 of mental
    health records although tobacco use more
    frequently documented
  • Peterson 2003, Am J Addiction
  • Few physicians treat smokers with psychiatric
    diagnoses - Primary care counseled more than
  • Thorndike 2001, NTR National Ambulatory Medical
    Care Survey 1991-1996
  • APA Psychiatric Research Network (Montoya et al)

Smoke-Free Inpatient Units
  • 1991 JCAHO policy change increased the awareness
    and need to address smoking
  • Inpatient units went tobacco-free
  • Going Smoke-Free does not cause new problems
  • No Increase in disruptive behaviors
  • No Increase in AMA discharges
  • No Additional seclusion and restraints
  • No Increase in use of PRN medications
  • Patten et al., 1995 Haller et al., 1996

Why Address?
  • Nicotine Dependence is an addiction a mental
  • Major Public Health concern need to reduce
    tobacco-caused medical illness and death, improve
    QOL and recovery
  • Second Hand Smoke Impacts Non-smokers
  • Smokers have a right to smoke (its legal) but
    there is a hierarchy of rights smokers also
    should have the right to compassion from others
    and the right for treatment and the right for
    legal action against the tobacco industry

Strategies to Treat Tobacco Addiction
  • 6 FDA approved Medications
  • other promising meds Nortriptyline, ? others
  • Psychosocial treatment
  • Behavioral therapies
  • Motivational Enhancement Therapies
  • Harm reduction versus Abstinence Goal

Evidence Based Studies in Schizophrenia
  • Nicotine Replacement Medications
  • Nicotine Patch
  • 5 published studies no placebo control
  • Numerous unpublished posters and clinical
  • All supportive
  • Nicotine Spray (3 small studies)
  • Nicotine Gum (1 small study)
  • Nicotine Inhaler and Lozenge Clinical
  • Bupropion (Zyban)
  • 3 Studies 2 with placebo
  • Behavioral Therapy Motivational Enhancement
    Therapy approaches 5 studies
  • Action stage
  • Precontemplator, Contemplators, and Preparation

Harm Reduction versus Abstinence
  • Formal studies needed
  • In abstinence oriented studies many patients
    are able to reduce the quantity and frequency of
    usage and increase their commitment to addressing
  • Many MH staff desire to use the harm reduction
  • Clinical approaches tried reducing number of
    cigarettes, switching some NRT for some
    cigarettes, behavioral modifications (not smoke
    in house, in car, etc). Compensatory change in
    smoking style to keep same nicotine levels is
    concern - TRACK biomarkers.
  • A motivation based option - ? Long-term or
    short-term harm reduction?? NRT maintenance

Rationale Pharmacology How much nicotine
  • Each cigarette contains about 13 mgs nicotine
  • about 1 3 mgs of nicotine are absorbed per
  • SMI tend to absorb the 2 - 3mgs nicotine per
  • Higher CO and Cotinine levels than expected
  • Some practitioners and researchers are matching
    nicotine level to nicotine replacement dosage
  • Example 3 packs per day 20 cigarettes times
    2 mgs per cigarette times 3 packs per day 120
    mgs nicotine

American Psychiatric Association Treatment
  • Treatment Guidelines for Psychiatric Disorders,
    including substance use disorders and nicotine
  • call APPI press 1-800-368-5777
  • also guidelines are published in the American
    Journal of Psychiatry (AJP)
  • Nicotine Dependence Guidelines in November 1996

Have Nicotine Dependence follow the same
Principles of Dual Diagnosis Treatment
  • Dual diagnosis changes treatment as usual
  • Integrate addiction treatment approaches
  • Match treatment to recovery stage and
    motivational level
  • Timing of treatments
  • Address tobacco across the continuum
  • Consider a long-term treatment perspective

Motivation Based Dual Diagnosis Treatment Model
  • Engagement Empathy
  • Match Goals and Techniques to 5 Stages
  • Precontemplation, contemplation, preparation,
    action, and maintenance
  • Services matched to motivational levels
  • healthy living groups
  • contemplation vs action phase specific treatments
  • Link with MICA treatments

  • Assist patient in developing a quit plan
  • Encourage nicotine replacement therapy
  • Provide practical problem-solving counseling
  • Provide supportive clinical environment
  • Help patient develop social support for quit
  • Provide supplementary materials

Setting a Target Quit Date
  • For those who are motivated to quit
  • Provides time and target date to mobilize
    resources for quitting
  • Date should allow for sufficient time to acquire
    skills for quitting

Arrange Follow-up
  • Arrange in-person or phone follow-up shortly
    after the quit date
  • Timing
  • One contact within a week after quit date
  • Second contact within the first month
  • At follow-up contact
  • Reinforce success
  • Problem-solve difficulties
  • Encourage view of slips as learning experiences
  • Assess nicotine replacement therapy
  • consider referral to intensive, specialized

NIDA Technology Model of Behavioral therapy
  • Specify Treatments
  • Manuals, dose, setting
  • Reduce Therapist Variability
  • Selection, training program
  • Standardize Treatment Delivery
  • Ongoing supervision, monitoring
  • Reduce Patient Heterogeneity
  • Optimize Outcome Measurement
  • multidimensional assessments, raters

4 Stages of NIDA Psychosocial Therapy Development
  • Stage I Demonstrate Premise. Develop
    manuals, adherence scales, training program,
    assess feasibility
  • Stage II Demonstrate Efficacy, RCT,
    component analysis (e.g.dismantling,
    predictor/matching, and optimization)
  • Stage III Demonstrate Generalizability across
    patients, therapists, and sites.
  • Stage IV Technology Transfer. Large Scale
    Training. Demonstration research

Adapting Motivational Enhancement Therapy for
Tobacco Dependence
  • Brief Therapy - 4 Sessions in Project MATCH
  • Blends MI and Feedback Tools
  • Tools Personalized Feedback Change Plan with
    Menu of Options
  • Focused Heavily on Developing Discrepancy
  • Use of decisional balance (pros / cons)
  • engaging a SO
  • Eliciting Change Talk
  • Provide feedback and promote self-efficacy

MET MI Feedback
  • Motivational Interviewing (Style)
  • Empathy, Client-Centered, Respects readiness to
    change, embraces ambivalence
  • Directive one problem focused (needs adaptation
    for poly-drug COD)
  • Personalized Feedback (Content)
  • Assessment
  • Personalized Feedback
  • Values / Decisional Balance Pros Cons
  • Change Plan Menu of Options

Steinberg ML, Ziedonis DM, Krejci JA, Brandon TH.
Journal of Consulting Clinical Psychology, in
  • Motivational Interviewing With Personalized
  • A Brief Intervention for Motivating Smokers With
    Schizophrenia To Seek Treatment for Tobacco

78 Smokers with Schizophrenia who were
unmotivated to quit
Minimal Control N12
Motivational Interviewing N32
Psychoeducation N34
One week and one month post-intervention follow-u
p by R.A. blind to treatment condition
Steinberg ML, Ziedonis DM, Krejci JA, Brandon TH.
Motivational Interviewing With Personalized
Feedback A Brief Intervention for Motivating
Smokers With Schizophrenia To Seek Treatment for
Tobacco Dependence. Journal of Consulting
Clinical Psychology, in press.
MI with Personalized Feedback Increases
motivation to quit at one week and one month
Personalized feedback what mattered
  • Carbon Monoxide score and feedback
  • Big impact on patients
  • Short-term benefits to quit
  • Cost of Cigarettes for the year
  • Medical conditions affected by tobacco
  • Links with other substances, relapses, etc

Clinical Implications
  • MI appears to be a better strategy than more
    commonly utilized techniques
  • Indicates this population can benefit from brief
  • Should offer brief interventions to engage in

Steinberg ML, Ziedonis DM, Krejci JA, Brandon TH.
Motivational Interviewing With Personalized
Feedback A Brief Intervention for Motivating
Smokers With Schizophrenia To Seek Treatment for
Tobacco Dependence. Journal of Consulting
Clinical Psychology, in press.
What Intensity of Treatment?
  • Studies underway
  • Different medications
  • Different psychosocial treatments
  • TANS (Treating Addiction to Nicotine in
    Schizophrenia) vs Medication Management

Medication issues
  • Primary antipsychotic
  • Atypicals versus Traditional antipsychotics
  • Other adjunctive medications to enhance cognition
    and reduce negative symptoms
  • Medication for Nicotine Dependence
  • NRT
  • Bupropion
  • Combinations
  • Others? Galantamine (Allen et al, 2002)
    Donepezil (cholinesterase inhibitor negative
  • NEED for Patient Education

Atypicals versus Typicals
  • Clozapine helps spontaneously reduce tobacco use
    (especially heavy smokers)
  • Marcus and Snyder, 1995
  • McEvoy et al, 1995
  • George et al, 1995
  • Use of atypicals improves outcomes versus
    traditionals in NRT tobacco dependence treatment
    study (George, Ziedonis, et al 2000)
  • Similar weight gain smokers and non-smokers with
    olanzapine vs risperidone (Lasser / Janssen

Nicotine Abstinence Rates at 12-weeks
  • Self-Report CO lt 10 ppm
  • 35 both therapy groups with NRT
  • (6/17 ALA 10/28 Specialized)
  • Specialized had significantly higher rates of
    continuous abstinence during the last 4 weeks
    compared to ALA
  • 22 Typical antipsychotic NRT
  • 56 Atypical antipsychotic NRT
  • 71 (5/7) Olanzapine
  • 60 (3/5) Risperidone
  • 50 (2/4) Clozapine

NRT for Schizophrenics
  • More research needed placebo controlled
  • NRT in variety of routes of administration,
    variable doses and duration for schizophrenic
  • Higher dose transdermal patch (42mg) and trials
    of longer duration (24 weeks) Jill Williams et
    al, 2004
  • In heavy smokers, under dosing may be one of the
    reasons for the limited efficacy of transdermal
  • Blood cotinine levels at baseline and steady
    state measures for assessing adequacy of nicotine

Nicotine Nasal Spray for Schizophrenia
  • NNS Rapid onset of action, intermittent dosing,
    and more immediate craving relief
  • Case series 12 schizophrenic smokers
  • failed prior treatments
  • well tolerated, 75 used at least 30 sprays per
    day, 25 continuously abstinence, 40 three
    months abstinent, 25 substantial CO lowering
    (21 to 3)
  • Williams, Ziedonis, Foulds, in press, Psych

Long-term NRT
  • The long term health effects of NRT are unknown
  • Felt to outweigh risks from exposure to carbon
    monoxide and carcinogens.
  • Long term use of the patch has not been a
  • Gum is almost never misused, thus lacking true
    abuse liability
  • Weaning of the gum usually requires only
    education and reassurance even in long term

What works for this population
  • Lead in Engagement Period using Motivational
    Enhancement Therapy - ? Harm reduction ?
  • Meds and therapy
  • Use of Nicotine Replacement and / or Zyban
  • Integrating behavioral therapy for more than 10
  • CBT / relapse prevention
  • Eclectic blends SST, ALA, support, educational
  • Follow-up Brief individual contact / sessions /
  • Group support
  • Community support
  • Peer support
  • Modified NicA
  • Multimodal presentation of material

Tactics of Treatment
  • Medications
  • Start Bupropion two weeks prior to quit date
  • Start NRT Patch on quit date
  • PDR versus Clinical Practice
  • Use of NRT prior to quit date as a replacement
    for cigarettes
  • Use of Bupropion plus patch (plus gum, etc)
  • Dosage of NRT
  • Use of multiple NRT strategies (multiple patches,
    multiple NRTs)
  • Length of time on NRT or Bupropion

Other Tactics
  • Primary antipsychotic choice
  • Intensity and type of psychosocial treatments
  • Tobacco Metabolism and Medications
  • Monitor side effects and dosage
  • Ongoing monitoring and reassessment
  • Critical periods first three days, first two
    weeks and first six months
  • CO, cotinine, and self-report of tobacco usage

Forced Abstinence (Environmental Tobacco Smoke
issue) on inpatient psych units
  • Assessment
  • Psychiatric management
  • System issues
  • Negotiating
  • Patient education
  • Monitoring
  • Use of Psychosocial treatments
  • Use of pharmacological therapies

Perceived Advantages to address tobacco on the
psychiatric inpatient unit
  • A healthier environment and health promotion
  • Consistency with other Center policy
  • May facilitate addressing nicotine dependence in
    patients at a later date
  • A safer environment with less likelihood of fires
  • An increase in involvement of smokers with
    activities other than smoking
  • A decrease is sub grouping smokers and
  • An opportunity for patients to learn healthier
    ways of coping with problems than by smoking

Perceived disadvantages to addressing tobacco on
the psychiatric unit
  • There might be an
  • increase in patient acting out
  • increase in rule infraction
  • increase in AMA discharges
  • Tobacco withdrawal may increase psychiatric
    symptoms and require more meds and restraints
  • Infringement of involuntary patients rights
  • Loss of business and decreased admissions
  • Medications will be needed to assist patients
    through smoking withdrawal on the unit
  • Antipsychotic medication blood levels will be
    less stable

UMDNJ Tobacco Program
  • Addressing Tobacco in MH Settings Agenda
  • 8 Day Specialist Training
  • Ongoing consultation and clinical suggestions
  • Tertiary treatment
  • Email listserve
  • Program Consultation Addressing Tobacco
  • N.J. Guidelines for Tobacco Dependence Treatment

NJ Experience
  • 60 system consultations to MH Agencies per year
    (mostly outpatient, some inpatient often linked
    with MICA staff Community Health Fairs -
  • Development of relationship with program
  • Starts with 11 consult
  • Big Packet sent with evidence based materials
  • Initial staff training onsite (3 hours)
  • F/U Support more trainings on site policy
    changes treatment supervision of groups /
    clinical consults
  • List Serve link
  • Manuals for treatment cookbooks ALA, Smoke
    Enders Trying to Kick Butts NicA
  • About 33 do our 5 or 8 day training after about
    6 months

NJ Experience
  • Want harm reduction strategies that decrease ETS
    risks (smoking in vehicles group homes)
  • Patients can be helped down to 10 cig / day
  • What are other programs doing?
  • Staff smokers (fewer than our consults to
    addiction programs)
  • Staff buy cigarettes for patients (internet, mail
    order, drive to reservations buy for group of
    patients starts through money management
    discussions credit cards)
  • Staff smokers referred to NJ network of free
    services for help
  • Staff reaction to posters in clinics
  • Few Tobacco Free Grounds
  • NRT resistant staff
  • Consumer Wellness Programs good opportunity
  • Evening and Weekends BIG triggers for patients

Addressing Tobacco in Smokers with Mental Illness
  • Consultation and Program Development
  • Single clinical site
  • Mental health agency
  • Professional organizations
  • Consumer advocacy organizations
  • Family advocacy organization
  • State Division of Mental Health Services

Program Level Changes to Address Tobacco (1st)
  • Acknowledge the challenge
  • Establish a leadership group and commitment to
  • Create a Change Plan and Implementation timeline
  • Start with the Easier System Changes
  • Conduct staff training
  • Provide Treatment and Recovery Assistance for
    interested nicotine dependent staff
  • Document Assessment and Treatment Planning

Program Level Changes to Address Tobacco (2nd)
  • Incorporate tobacco issues into patient education
  • Provide Medications for Nicotine Dependence
    Treatment and Required Abstinence Periods
  • Integrate Motivation-Based Treatments throughout
  • Develop onsite Nicotine Anonymous meetings and
    establish ongoing communication with 12-Step
    Recovery groups, professional colleagues, and
    referral sources about system change
  • Develop Addressing Tobacco Policies and clear
  • A BIG next step Creating a totally Tobacco-Free
  • Tobacco-free facility and grounds
  • Implement comprehensive approach

Consumer advocacy organizations
  • Mental Health Association of New Jersey
  • Create a consumer advocacy movement for tobacco
    services in NJ
  • Consumer connections
  • Consumer forums
  • Wellness forums
  • Outreach to self-help centers

Stigma/ Counter-Advocacy
  • Tobacco is devalued not acute problem
  • Misinformation is common
  • Family and professional advocates protecting use
    of tobacco
  • Patients seeking employment see smokers as being
    stigmatized and this is a reason to quit smoking

Specialist Tobacco Treatment Centers www.tobaccopr