Addressing Co-Occurring Schizophrenia and Nicotine Dependence

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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

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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
  help
• Medications Behavioral therapy are effective
• Also need Program System changes culture,
  policy enforcement, training, funding, and
  staff training

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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

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Addressing Tobacco in Addiction and Mental Health
Settings

• 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

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Unique Features of Schizophrenia

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

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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

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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

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Tobacco Smoking Effects Some Psychiatric
Medication Blood Levels

• Smoking induces the P450s 1A2 isoenzyme
  secondary to the polynuclear aromatic
  hydrocarbons
• Smoking increases the metabolism of some
  medications
• 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
  (2D6)
• NRT doesnt effect medication blood levels
• Nicotine may modulate cognition, psychiatric
  symptoms, and medication side effects

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Are patients better off smoking?

• Nicotine modulates both dopamine and glutamate
• Nicotinic acetylcholine receptors on dopamine
  neurons
• Stimulates glutamate neurons in prefrontal cortex
• Schizophrenia gene defect low alpha 7 Nic
  receptors
• 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)

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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?

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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

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Steinberg, M. L., Williams, J. M., Ziedonis, D.
M. (2004). Financial Implications of Cigarette
Smoking Among Individuals With Schizophrenia.
Tobacco Control, 13(2).
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Tobacco use increases alcohol and other drug use
intake and cravings

• Tobacco Craving Laboratory with schizophrenic
  smokers
• Animal and human laboratory research on effect of
  tobacco use on increasing consumption and
  cravings.
• Tobacco use correlates in dose-dependent fashion
  with cocaine and heroin use
• Frosch, Shoptaw, Nahom, Jarvik, Exptl Clin
  Psychopharm. 2000 897-103

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Why the high rates of nicotine dependence among
these groups ?

• Biological / Genetic
• Psychological (Self-Medication?)
• Social / Environmental / Cultural
• Institutional / MH System Factors

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Hypotheses for initiation, maintenance, and
difficulty quitting

• Increased propensity to dependence?
• Illness modulation effect?
• Side effect reduction?
• Immediate
• self-medicating
• effect?
• Social factors?

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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

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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
  functions
• This receptor is involved in the sensory gating
  deficit (abnormal P50 auditory-evoked potential)
• (R. Freedman, U of Colorado)

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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)

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Social Factors

• Cultural differences
• Japanese patients with schizophrenia tobacco
  dependence at 34 similar to the general
  population
• 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

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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
  time?
• Interestingly, patients have reported feeling
  less stigmatized when they smoke (promote sense
  of freedom).

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Institutional Barriers to Tobacco Dependence
Treatment

• 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
  cigarettes
• Restrictive formulary or insurance coverage of
  the cost of medications
• Limited income and cannot afford OTC medications

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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
  psychiatrists
• Thorndike 2001, NTR National Ambulatory Medical
  Care Survey 1991-1996
• APA Psychiatric Research Network (Montoya et al)

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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

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Why Address?

• Nicotine Dependence is an addiction a mental
  illness
• 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

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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

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Evidence Based Studies in Schizophrenia

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

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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
  tobacco
• Many MH staff desire to use the harm reduction
  approach
• 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
  options?

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Rationale Pharmacology How much nicotine
consumed?

• Each cigarette contains about 13 mgs nicotine
• about 1 3 mgs of nicotine are absorbed per
  cigarette
• SMI tend to absorb the 2 - 3mgs nicotine per
  cigarette
• 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

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American Psychiatric Association Treatment
Guidelines

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

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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

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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
• NICOTINE ANONYMOUS

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MANAGEMENT Assist

• 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

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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

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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
  program

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NIDA Technology Model of Behavioral therapy
Research

• 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

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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

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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

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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

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Steinberg ML, Ziedonis DM, Krejci JA, Brandon TH.
Journal of Consulting Clinical Psychology, in
press

• Motivational Interviewing With Personalized
  Feedback
• A Brief Intervention for Motivating Smokers With
  Schizophrenia To Seek Treatment for Tobacco
  Dependence

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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.
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MI with Personalized Feedback Increases
motivation to quit at one week and one month
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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

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Clinical Implications

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

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.
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What Intensity of Treatment?

• Studies underway
• Different medications
• Different psychosocial treatments
• TANS (Treating Addiction to Nicotine in
  Schizophrenia) vs Medication Management

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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
  study).
• NEED for Patient Education

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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
  study)

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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

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NRT for Schizophrenics

• More research needed placebo controlled
• NRT in variety of routes of administration,
  variable doses and duration for schizophrenic
  patients
• 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
  nicotine
• Blood cotinine levels at baseline and steady
  state measures for assessing adequacy of nicotine
  replacement

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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
  Services

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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
  problem.
• Gum is almost never misused, thus lacking true
  abuse liability
• Weaning of the gum usually requires only
  education and reassurance even in long term
  users.

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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
  weeks
• CBT / relapse prevention
• Eclectic blends SST, ALA, support, educational
  sessions
• Follow-up Brief individual contact / sessions /
  phone
• Group support
• Community support
• Peer support
• Modified NicA
• Multimodal presentation of material

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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

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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

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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

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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
  non-smokers
• An opportunity for patients to learn healthier
  ways of coping with problems than by smoking

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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

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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
• www.tobaccoprogram.org

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NJ Experience

• 60 system consultations to MH Agencies per year
  (mostly outpatient, some inpatient often linked
  with MICA staff Community Health Fairs -
  Wellness)
• 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

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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

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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

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Program Level Changes to Address Tobacco (1st)

• Acknowledge the challenge
• Establish a leadership group and commitment to
  change
• 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

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Program Level Changes to Address Tobacco (2nd)

• Incorporate tobacco issues into patient education
  curriculum
• Provide Medications for Nicotine Dependence
  Treatment and Required Abstinence Periods
• Integrate Motivation-Based Treatments throughout
  system
• 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
  consequences
• A BIG next step Creating a totally Tobacco-Free
  Environment
• Tobacco-free facility and grounds
• Implement comprehensive approach

65
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

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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

67
THREE LEVELS OF TREAMENTQUIT CENTERS
Specialist Tobacco Treatment Centerswww.tobaccopr
ogram.org