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Excess Mortality and Metabolic Risks in Psychosis

Excess Mortality and Metabolic Risks in Psychosis. Urban Ösby MD, PhD, Senior Consultant Psykiatri Nordväst, Stockholm County Council Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. urban.osby@sll.se.

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Excess Mortality and Metabolic Risks in Psychosis

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  1. Excess Mortality and Metabolic Risks in Psychosis Urban Ösby MD, PhD, Senior Consultant Psykiatri Nordväst, Stockholm County Council Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden urban.osby@sll.se

  2. SMR (Observed/Expected) and Excess deaths (Observed-Expected) for patients with schizophrenia in Stockholm County 1973-95 Ref: Osby U, et al. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophr Res 2000;45(1-2):21-8.

  3. Natural 264 47% Excess deaths by natural and unnatural causes for schizophrenia patients in Stockholm County 73-95 Men Women Unnatural 218 38% Natural 352 62% Unnatural 296 53% Ref: Osby U, et al. Mortality and causes of death in schizophrenia in Stockholm county, Sweden. Schizophr Res 2000;45(1-2):21-8.

  4. SMR (O/E) and Excess deaths (O–E) for patients with bipolar disorder in Sweden 1973-95 Ref: Osby U, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58(9):844-50.

  5. SMR (O/E) and Excess deaths (O-E) for patients with unipolar disorder in Sweden 1973-95 Ref: Osby U, et al. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58(9):844-50.

  6. Mortality in the population in Stockholm County Standardized by the sex- and age distribution of patients with schizophrenia in Stockholm County 1976-95 Deaths/100 000 1000 900 800 700 All deaths Natural causes of death 600 500 400 300 Cardiovascular deaths 200 100 Violent deaths Suicide 0 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95

  7. Mortality trends in Stockholm county 1976-94, all causes of death Deaths/100 000 1976 year of reference 1.4 Patients with schizophrenia* 1.2 1 0.8 General population** 0.6 0.4 0.2 0 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients Ref: Osby U, et al. Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study. Bmj 2000;321(7259):483-4.

  8. Mortality trends in Stockholm county 1976-79 to 1990-95, natural causes of death Deaths/100 000 76-79 period of reference 1.4 Patients with schizophrenia* 1.2 1 0.8 General population** 0.6 0.4 0.2 0 76-79 80-85 86-89 90-95 * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients

  9. Mortality trends in Stockholm County 1976-79 to 1990-95, cardiovascular causes of death Deaths/100 000 76-79 period of reference 1.4 Patients with schizophrenia* 1.2 1 0.8 0.6 General population** 0.4 0.2 0 76-79 80-85 86-89 90-95 * Controlling for age at first diagnosis and years of follow-up **Standardized by the sex and age distribution of the patients Ref: Osby U, et al. Time trends in schizophrenia mortality in Stockholm county, Sweden: cohort study. Bmj 2000;321(7259):483-4.

  10. Mortality trends in Sweden 1970-2003 (adjusted for age)

  11. Mortality trends in Sweden 1970-2003 (adjusted for age)

  12. SMR for schizophrenia for all causes of death, cardiovascular causes, coronary heart disease, and myocardial infarction

  13. Time trends for SMR for all causes of death for schizophrenia in Sweden (p<.0001)

  14. Time trends for SMR for cardiovascular death for schizophrenia in Sweden (p<.0001)

  15. Time trends for SMR for death from coronary heart disease for schizophrenia in Sweden (p<.0001)

  16. Time trends for SMR for death from myocardial infarction for schizophrenia in Sweden (p<.0001)

  17. Reduced life expectancy in schizophrenia Men Women Schizophrenia 56.2 66.1 Population 72.0 79.1 • ”… The net result is not only shortened survival and decreased quality of life for those with schizophrenia due to the burden of untreated medical conditions, but also functional impairment and a direct adverse impact on psychiatric symptoms…” • Meyer & Nasrallah 2003

  18. Cardiovascular Risk Factors (Estimated Prevalence % and Relative Risk RR) (Newcomer: National Forum on Medical co-morbidities, New York 2005)

  19. Psychotropic-Associated Weight Gain (Newcomer: National Forum on Medical co-morbidities, New York 2005)

  20. Mean Change in Weight With Antipsychotics

  21. Clinically significant (>7%) weight gain during treatment with atypical antipsychotics (data from US labels) % who gained more than 7% of body weight Olanzapine1 Risperidone2 Quetiapine3 Aripiprazole4 Ziprasidone5 1. Olanzapine( Zyprexa) U.S Prescribing Information 2. Risperidone (Risperdal) U.S Prescribing Information 3. Quetiapine (Seroquel) U.S Prescribing Information 4. Aripiprazole (Abilify) U.S Prescribing Information. 5 Ziprasidone (Geodon) U.S Prescribing Information

  22. Clinically Significant (7%) WeightGain During Antipsychotic Treatment Incidence (%) Abilify [package insert]. Princeton, NJ: Bristol-Myers Squibb Company and Rockville, MD: Otsuka Pharmaceutical, Inc.; 2002. Geodon [package insert]. New York, NY: Pfizer Inc; 2002. Risperdal [package insert]. Titusville, NJ: Janssen Pharmaceutica Products LP; 2002. Seroquel [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2001. Zyprexa [package insert]. Indianapolis, IN: Eli Lilly and Company; 2002.

  23. Early Identification of Patients with Schizophrenia at Risk for Substantial Weight Gain on Olanzapine Mean Weight Change (kg) 7% change in 6 weeks (n=183 <7% change in 6 weeks (n=1008) Weeks Kinon BJ, et al. J Clin Psychopharm. 2005; 25(3):255-259.

  24. Antipsychotic drugs and diabetes ”…In one institution, the prevalence of type-2 diabetes in female in-patients with schizophrenia rose from 4.2 % in 1956 to 17.2 % in 1968…” Thonnard-Neumann 1968

  25. ”… Diabetes is a disease which often shows itself in families in which insanity prevails…” Sir Henry Maudsley 1879

  26. Metabolic risks in Psychosis 1. Metabolic adverse effects of antipsychotic, mood stabilizing and anti-depressant medication – weight gain, DM, lipid disturbances, etc 2. Life style factors related to the disease – increased smoking, increased alcohol use, less exercise, etc 3. Overlapping risk genes between psychiatric and metabolic disorders?

  27. Swedish study of metabolic risks in psychosis • Population-based recruitment from psychosis outpatient departments • Prospective design with three years follow-up. Drug-naive patients included separately. • Assessments: 1) Diagnosis, social function (GAF+CGI), present and previous medication; 2) Weight, waist circumference, BMI, BP; 3) Somatic health: DM, cardiovascular disease, smoking, alcohol use etc. Lab: 1) clinical: Hb, glucose, lipids, TSH, etc; 2) research: serum + plasma + blood for DNA

  28. The study will assess: • Metabolic risk profiles in psychosis patients compared to the population • Relative effects of medication and life style factors on metabolic risks in psychosis • Effects of prospective screening for metabolic risks • Genetic markers for risk (5-HT2C, leptin) and outcome (5-HT1A) • Reported medication compared with serum levels and metabolizing enzymes • Quality of life (EQ5D) compared to the population and related to overweight and medication

  29. Psychiatric diagnosis (n=642) Schizophrenia 342 53 % Schizoaffective disorder 64 10 % Delusional disorder 36 6 % Psychosis NOS 80 12 % Bipolar disorder 40 6 % Other/ND 80 12 %

  30. Psychiatric history (n=642) • Men Women Age (year) 46.4 49.9 Age at debute (med) 28.4 30.0 Age at start of treatment 29.5 32.0 Months in hospital 12.4 11.4 GAF 50.3 53.2

  31. Overweight and obesity (n=642) • Men Women BMI (kg/m2) 28.3 28.8Waist (cm) 104.4 96.5

  32. BMI in psychosis and population (Population from Public Health Report 2003)

  33. BMI distribution for men and women

  34. BMI before (reported) and after (measured) treatment for men

  35. BMI before (reported) and after (measured) treatment for women

  36. Reported weight gain after psychiatric treatment

  37. Diabetes and fasting glucose levels (n=642) Total sample (n=642): • 239 patients pathologic glucose levels: • 53 patients fP-Glucos > 7: 8.3 % • 185 patients fP-Glucos 5,6–6,9: 28.8 % Without known DM (n=585, 91.1 %): • 25 patients fP-Glucos > 7: 4.3 % • 167 patients fP-Glucos 5,6–6,9: 28.5 %

  38. Metabolic syndrome according to IDF criteria (n=642)

  39. Metabolic syndrome according to IDF criteria (n=642)

  40. Smoking (n=642) Present smokers 285 44.4 % Previous smokers 156 24.3 % Never smoked 192 29.9 % Years of smoking men: 20.9 women: 24.2

  41. Reported somatic disorders (n=642) MI 11 1.7 % Elevated BP 102 15.9 % DM 57 8.9 % Elevated lipids 84 13.1 %

  42. Heredity for metabolic disorders (n=642) Cardiac disorder 280 43.6 % Elevated BP 248 38.6 % DM 153 23.8 % Obesity 180 28.0 %

  43. Present antipsychotic medication (n=403) 0 drug: 31 7.7 % 1 drug: 325 80.6 % 2 drugs: 43 10.7 % 3+ drugs: 4 1.0 %

  44. Present antipsychotic drugs (n=642) Olanzapine 121 18.8 % Risperidone 112 17.4 % Aripiprazol 73 11.4 % Haloperiodol 65 10.1 % Perfenazin 70 10.9 % Zuclopentixol 60 9.3 % Clozapine 47 7.3 % Quetiapine 33 5.1 % Flupentixol 23 3.6 % Other/ND 49 7.7 %

  45. Reported general health

  46. Clinical Decision Making: Weighing Risks and Benefits

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