1. What Kills People with Psychiatric Conditions or Alcohol/Drug-use Disorders? An Assessment of Mortality Records RUSS CALLAGHAN, PHD ASSOCIATE PROFESSOR NMP JODI GATLEY, BSC RESEARCH ANALYST UNBC

2. KEY QUESTIONS What conditions contribute to the greatest burden of mortality in these populations? Does tobacco-related mortality comprise a substantial proportion of deaths in these populations?

3. TOBACCO-RELATED MORTALITY CONDITIONS Malignant Neoplasms Cardiovascular Disease Respiratory Diseases Acute myeloid leukemia Bladder Cervix uteri Esophagus Larynx Pancreas Stomach Kidney and renal pelvis Lip, oral cavity and pharynx Trachea, bronchus and lung Aortic aneurysm and dissection Atherosclerosis Cerebrovascular diseases Ischaemic heart disease Other diseases of arteries, arterioles and capillaries Chronic airway obstruction Bronchitis or emphysema Influenza or pneumonia INTERNATIONAL AGENCY FOR RESEARCH ON CANCER Centers for Disease Control (CDC)

4. SMOKING AMONG INDIVIDUALS WITH PSYCHIATRIC DISORDERS a de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research 2005;76(2-3):135-57. b Lawrence D, Mitrou F, Zubrick SR. Smoking and mental illness: results from population surveys in Australia and the United States. BMC Public Health 2009;9:285.

5. SMOKING AMONG INDIVIDUALS WITH ALCOHOL- AND DRUG-USE DISORDERS a Yadav,D.,Eigenbrodt,M.L.,Briggs,M.J.,Williams,D.K.,Wiseman,E.J. (2007) Prevalence and risk factors among male veterans in a detoxification program. Pancreas, 34(4):390-98. b Patten,C.A.,Hurt,R.D.,Offord,K.P.,Croghan,I.T.,Gomez-Dahl,L.C.,Kottke,T.E.,Morse,R.M.,Melton,L.J. (2003).Relationship of tobacco use to depressive disorders and suicidality among patients treated for alcohol dependence. American Journal on Addictions, 12(1): 71-83. c Chatham,L.R., Hiller, M.L., Rowan-Szal, G.A., Joe, G.W., Simpson, D. gender differences and admission and follow-up in a sample of methadone maintenance clients. (1999). Substance Use & Misuse, 34(8): 1137-65. d Heinzerling, K.G., Swanson, A-N., Kim, S., Cederblom, L., Moe, A., Ling, W., Shoptaw, S. (2010). Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence. Drug and Alcohol Dependence, 109(1-3): 20-9. e Budney, A.J., Moore, B.A., RocHa, H.L., Higgins, S.T. (2006). Clinical trial of abstinence-based vouchers and cognitive-behavioral therapy for cannabis dependence. Journal of Consulting and Clinical Psychology, 74(2):307-16.

6. Hurt et al. 1996 Individuals (n = 845; 65% men) from Minnesota in residential addiction treatment primarily for alcohol-use problems, 22-year follow-up 51% of cumulative mortality (222 total deaths) was due to tobacco-related conditions—a rate surpassing that from alcohol-related conditions, 34% of the deaths Hser et al. 1994 Male narcotic offenders (n = 405) from California mandated to inpatient/outpatient treatment primarily for heroin dependence, 20-year follow-up Current smokers had a four-fold higher death rate than nonsmokers 16% of the cumulative mortality was tobacco-related (77 total deaths) Limitations: Small, primarily male samples; small number of outcome mortality events; a focus on patterns of tobacco-related deaths only among individuals with primary alcohol or heroin problems; and lack of a matched population-based comparison groups. There is surprisingly little research assessing tobacco-related mortality among individuals with alcohol- or drug-use problems

7. Many cohort studies have shown an increased all-cause and cause- specific mortality for patients with: Schizophrenia - Hennekens et al., 2005; Tran et al., 2009; Brown et al., 2010; Casey et al., 2011; Saha et al., 2007; Auquier et al., 2007 Bipolar disorder - Heffner et al., 2011; Chang et al., 2012; Osby et al., 2001 Depression - Chang et al., 2012; Laursen et al., 2007; Mykletun et al., 2007) Limitations: Problems in the definition of psychiatric cohorts; a lack of coverage and/or differentiation of the full set of specific tobacco-related outcome conditions; and a lack of assessment into older adulthood, when tobacco-related conditions usually appear. Large literature on mortality among individuals with psychiatric disorders, BUT few studies specifically addressed tobacco-related mortality Large literature on mortality among individuals with psychiatric disorders, BUT few studies specifically addressed tobacco-related mortality

8. CURRENT STUDY: PSYCHIATRIC DISORDERS Schizophrenia Major Depressive Disorder Bipolar Disorder Image sources: http://www.medstorerx.com/mental-health/bipolar-disorder-the-symtoms-and-treatments.aspx; http://www.tappmedical.com/depression.htm ; http://www.drugfreehomes.org/2011/01/study-antipsychotic-drugs-not-being- prescribed-for-intended-use.htmlhttp://www.medstorerx.com/mental-health/bipolar-disorder-the-symtoms-and-treatments.aspx http://www.tappmedical.com/depression.htmhttp://www.drugfreehomes.org/2011/01/study-antipsychotic-drugs-not-being- prescribed-for-intended-use.html

9. ALCOHOL/DRUG (AOD) DISORDERS Methamphetamine Alcohol Cocaine Opioids Marijuana Image sources: http://www.treatment4addiction.com/addiction/intravenous-drug-use/ ; http://www.chroniclejournal.com/publications/horizons/issues/2012/june/articles/moderate-alcohol-consumption-beneficial ; http://www.nj.com/politics/index.ssf/2013/04/police_can_arrest_people_who_a.html ; http://www.kickoff.net.au/Drugs/Cocaine// ; http://www.pentagonpost.com/fda-opioids-analgesics/83411804/http://www.treatment4addiction.com/addiction/intravenous-drug-use/ http://www.chroniclejournal.com/publications/horizons/issues/2012/june/articles/moderate-alcohol-consumption-beneficial http://www.nj.com/politics/index.ssf/2013/04/police_can_arrest_people_who_a.html http://www.kickoff.net.au/Drugs/Cocaine//http://www.pentagonpost.com/fda-opioids-analgesics/83411804/

10. PATTERNS OF TOBACCO-RELATED MORTALITY AMONG INDIVIDUALS DIAGNOSED WITH SCHIZOPHRENIA, BIPOLAR DISORDER, OR DEPRESSION Materials and Methods Data: California Office of Statewide Health Planning and Development (OSHPD) inpatient hospital admission data from January 1, 1990 until December 31, 2005 from the Patient Discharge Database (PDD). Sample: Individuals who were at least 35 years old at the mid-point of their follow-up period. Outcomes: Mortality from tobacco-related conditions defined by the Centers for Disease Control and Prevention as causally related to tobacco use. Analytic Strategies: We produced SMRs using standardization, stratified by age, race and gender. We used the California general population in 2000 as the reference population, SchizophreniaBipolarMajor Depression Total Sample Size172,72276,098328,527

11. Proportion of mortality from tobacco related conditions across psychiatric disorder cohorts From: Callaghan, et al. in press, Journal of Psychiatric Research

12. Standardized mortality ratios (SMRs) for all tobacco-related mortality conditions across psychiatric disorder cohorts Standardized mortality ratios (SMRs) for all tobacco-related mortality conditions across psychiatric disorder cohorts From: Callaghan, et al. in press, Journal of Psychiatric Research

13. Standardized mortality ratios (SMRs) for tobacco-related mortality from all malignant neoplasms, cardiovascular disease, and respiratory diseases across psychiatric disorder cohorts From: Callaghan, et al. in press, Journal of Psychiatric Research

14. Excess mortality from all three major disease categories in all cohorts, except cancer in the bipolar group Highest tobacco related SMRs in the schizophrenia cohort, followed by the major depression and bipolar disorder cohorts SMRs among males and females were similar to the combined sample All respiratory diseases were associated with increased mortality in all cohorts, as were all cardiovascular diseases (except aortic aneurysm, which was not significantly elevated in any cohort, and ‘other arterial diseases’, which was not elevated in the Bipolar group). Cancers most strongly linked with smoking (including cancers of the lung, of the larynx, and of the pharynx, lip, or oral cavity) were associated with excess deaths in most cases. KEY RESULTS PSYCHIATRIC DISORDERS: SUMMARY

15. THE PROMINENCE OF TOBACCO-RELATED MORTALITY AMONG INDIVIDUALS WITH ALCOHOL- OR DRUG-USE DISORDERS Materials and Methods Data: California Office of Statewide Health Planning and Development (OSHPD) inpatient hospital admission data from January 1, 1990 until December 31, 2005 from the Patient Discharge Database (PDD). Sample: Outcomes: Mortality from tobacco-related conditions defined by the Centers for Disease Control and Prevention as causally related to tobacco use. Analytic Strategies: We produced SMRs using direct standardization. Data was stratified by age, race and gender. We used the California general population in 2000 as the reference population, obtaining relevant demographic and mortality data from the Centers for Disease Control and Prevention Wonder System. We derived smoking-attributable mortality (SAM) using the following attributable-fraction (SAF) formula from the Centers for Disease Control. AppendicitisMethamphetamineAlcoholCocaineOpioidMarijuana Total Sample Size 123,32936,717509,42235,27653,17215,995

16. Proportion of mortality from tobacco related conditions across alcohol- and drug- use and appendicitis cohorts Proportion of mortality from tobacco related conditions across alcohol- and drug- use and appendicitis cohorts From: Callaghan, et al. Unpublished

17. Proportion of deaths attributable to smoking in alcohol- and drug-use and appendicitis cohorts, unadjusted Proportion of deaths attributable to smoking in alcohol- and drug-use and appendicitis cohorts, unadjusted From: Callaghan, et al. Unpublished Meth = Methamphetamine

18. Proportion of deaths attributable to smoking, appendicitis-drug cohort groups matched by age, sex and race Proportion of deaths attributable to smoking, appendicitis-drug cohort groups matched by age, sex and race From: Callaghan, et al. Unpublished

19. Standardized mortality ratios (SMRs) for tobacco-related conditions across alcohol- and drug-use and appendicitis cohorts From: Callaghan, et al. Unpublished

20. Standardized mortality ratios (SMRs) for tobacco-related mortality from all malignant neoplasms, cardiovascular disease, and respiratory diseases across alcohol- and drug-use and appendicitis cohorts From: Callaghan, et al. Unpublished

21. KEY RESULTS DRUG- AND ALCOHOL-USE DISORDERS: SUMMARY Excess mortality from all three major disease categories in all alcohol- and drug-use cohorts Highest tobacco related SMRs in the opioid cohort, lowest in the cocaine cohort All respiratory diseases were associated with increased mortality in all cohorts, as were all cardiovascular diseases except atherosclerosis, which was not significantly elevated in the methamphetamine cohort. Cancers most strongly linked with smoking (including cancers of the lung, of the larynx, and of the pharynx, lip, or oral cavity) were associated with excess deaths in most cases. SAF adjusted mortality ranged from 20.5%-25.4% across cohorts compared to 11.1%-16% in the control appendicitis cohort

22. CAN-ADAPTT: CANADIAN SMOKING CESSATION CLINICAL PRACTICE GUIDELINE CAN-ADAPTT. (2011). Canadian Smoking Cessation Clinical Practice Guideline. Toronto, Canada: Canadian Action Network for the Advancement, Dissemination and Adoption of Practice-informed Tobacco Treatment, Centre for Addiction and Mental Health http://www.strokebestpractices.ca/wp-content/uploads/2012/04/CAN-ADAPTT2.pdf Summary Statements for Mental Health and/or Other Addiction(s): 1)Health care providers should screen persons with mental illness and/or addictions for tobacco use. 2)Health care providers should offer counselling and pharmacotherapy treatment to persons who smoke and have a mental illness and/or addiction to other substances. 3)While reducing smoking or abstaining (quitting), health care providers should monitor the patients’/clients’ psychiatric condition(s) (mental health status and/or other addiction(s)). Medication dosage should be monitored and adjusted as necessary.

23. TOBACCO CESSATION TREATMENT TECHNIQUES: PSYCHIATRIC DISORDERS a Major Depressive Disorder Increased treatment length and intensity differentially improved abstinence outcomes of individuals with major depression Cognitive Behavioural Therapy (CBT) is effective for individuals with recurrent depressive episodes Nicotine gum may be effective Individuals who received an intervention including motivational counseling, nicotine patches and CBT counseling had high abstinence rates at 12 months (20% vs 13% control) and 18 months (25% vs 19% control) a Schizophrenia Nicotine replacement therapy (NRT) is an important component Intervention abstinence rates from 7% to 16% Buproprion and Varenicline may be effective pharmacological treatments b Bipolar Disorder Buproprion and Varenicline may be effective pharmacological treatments a Hall SM, Prochaska JJ. Treatment of smokers with co-occurring disorders: emphasis on integration in mental health and addiction treatment settings. Annual Review of Clinical Psychology 2009;5:409-31. b George TP, Wu BS, Weinberger AH. A review of smoking cessation in bipolar disorder: implications for future research. Journal of Dual Diagnosis 2012;8(2):126-30.

24. TOBACCO CESSATION TREATMENT TECHNIQUES: ALCOHOL- AND DRUG-USE DISORDERS Hall SM, Prochaska JJ. Treatment of smokers with co-occurring disorders: emphasis on integration in mental health and addiction treatment settings. Annual Review of Clinical Psychology 2009;5:409-31. Smoking abstinence can be achieved both during other drug/alcohol-use treatment or during the recovery period Most studies indicate that smoking cessation does not affect other substance cessation Individual behavioural counseling and NRT are effective

25. A Hall SM, Prochaska JJ. Treatment of smokers with co-occurring disorders: emphasis on integration in mental health and addiction treatment settings. Annual Review of Clinical Psychology 2009;5:409-31. b Banham L, Gilbody S. Smoking cessation in severe mental illness: what works? Addiction 2010;105(7):1176- 89. Alcohol- and Drug- Use Disorder a Psychiatric Disorder b Short Term Cessation (<6 months) 12% vs 3% control11%-50% vs 4%- 19% control Long Term Cessation (≥ 6 months) Not significant3%-12% vs 1%-8% control Rates of smoking cessation with concurrent tobacco cessation treatment among individuals in treatment for alcohol- and drug-use disorders or psychiatric disorders

26. Conclusions Deaths from tobacco-related conditions contribute one of the largest burdens to overall mortality among individuals with psychiatric or alcohol/drug disorders. Smoking-cessation treatments are usually neglected in these populations, but times are changing…. Given the substantial burden of tobacco-related mortality, assessment of nicotine dependence and provision of appropriate smoking-cessation treatments should be considered an integral part of treatment protocols for these populations.