Addressing Co-Occurring Schizophrenia and Nicotine Dependence

1. 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

2. 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

3. 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 • SAMHSA’s 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

4. 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

5. 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)

6. 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

7. 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

8. Tobacco Smoking Effects Some Psychiatric Medication Blood Levels • Smoking induces the P450’s 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 doesn’t effect medication blood levels • Nicotine may modulate cognition, psychiatric symptoms, and medication side effects

9. 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)

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

11. 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 thegeneral population • Higher standardized mortality rates than general pop for: • Cardiovascular disease 2.3x • Respiratory disease 3.2x -Brown et al., 2000; Br J Psychiatry

13. Steinberg, M. L., Williams, J. M., & Ziedonis, D. M. (2004). Financial Implications of Cigarette Smoking Among Individuals With Schizophrenia. Tobacco Control, 13(2).

14. 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; 8:97-103

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

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

17. 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

19. 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)

20. 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)

21. 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”

22. 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).

23. 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

24. 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, N&TR; National Ambulatory Medical Care Survey 1991-1996 • APA Psychiatric Research Network (Montoya et al)

25. 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

26. 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 (it’s 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

27. 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

28. 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

29. 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?

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 78 Smokers with Schizophrenia who were unmotivated to quit Minimal Control N=12 Motivational Interviewing N=32 Psychoeducation N=34 One week and one month post-intervention follow-up 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.

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

44. 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

45. 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.

46. What Intensity of Treatment? • Studies underway • Different medications • Different psychosocial treatments • TANS (Treating Addiction to Nicotine in Schizophrenia) vs Medication Management

47. 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

48. 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)

49. Nicotine Abstinence Rates at 12-weeks • Self-Report & CO < 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

50. 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