Physical Health Of Patients With Schizophrenia

1. Physical Health Of PatientsWith Schizophrenia Dr. Ahmed Shoka Consultant Psychiatrist

4. Schizophrenia Strikes one in a hundred And affects many more.

6. The Mission • Facts • Figures • Findings • Challenge • Implication

7. The Concept • Physical medicine is becoming more psychological and Psychiatry is becoming more biological ( Physical) ?

8. Physical Examination • Many psychiatrists have not used a stethoscope, let alone done a physical examination, for many years. • Past surveys reported that most psychiatrists did not examine their patients routinely ( McIntyre & Romano, 1977), Summers et al, 1981 • Krummel & Kathol, 1987 found that a third had little confidence in their ability to do so or believed that it should be done by a physician other than a psychiatrist.

9. 57.6% of inpatients receive a comprehensive physical examination.

10. Alarming Figures • It has been reported that between 6 and 20% of patients with physical illness are misdiagnosed as having mental disorder, Koranyi, 1979; Koran et al, 1989. • Studies have shown that , in many cases, physical diseases will not be diagnosed and treated when a patient is admitted to a psychiatric unit , Felker et al, 1996 • Age-adjusted annual death rates from all causes among psychiatric patients are 2-4 times higher than in general population ( Harris&Baraclough 1998) with higher rates of physical disorders across the entire range of mental disorders.

11. Koranyi EK 1979 • 1-Causative physical illnesses: these comprise medical disorders that are entirely responsible for the psychiatric symptoms experienced by the patient • 2-Aggravating physical illnesses: disorders that augment an otherwise independently existing psychiatric disorder • 3-Co-existing physical illnesses: disorders that have relatively little or no impact on the psychiatric condition

12. The Principle

13. Introduction • Individuals with schizophrenia have a 20% shorter life expectancy than the population at large and a greater vulnerability to several illnesses, including diabetes, coronary heart disease, hypertension, obesity and emphysema. • The Mount Sinai Conference, held October 2002 in New York raised the issue that the health needs of people with schizophrenia who take antipsychotic medications typically are not adequately addressed by clinicians in mental health programmes or in primary care settings.

14. Excessive Mortality and Morbidity • Brown (97) noted that 25% patients with schizophrenia in a study from 1841 experienced mortality at between 3 and 14 times the rate seen in general population. • Three reviews that summarised results from studies conducted between 1942 and 1996 found the mortality rate in schizophrenia to be between 1.5 and 2 times than expected. • Examining sudden- death cases also demonstrates the increase in mortality associated with schizophrenia. • Patients with schizophrenia were overrepresented in the “undetermined cause of death” group in cases examined by the coroner’s office, Victoria, Australia during 1995

15. Remember • Reviews consistently find that suicide accounts for some of the increased mortality rate seen in schizophrenia ( Allebeck 89, Harris & Barraclough 98). • Suicide risk is greater early in the course of illness and close to hospital discharge • The risk of suicide appears to be increasing , perhaps related to greater reliance on less intensive treatment emphasising outpatient care ( Allebeck 89, Osby et al 2000 )

16. Morbidity • In reviewing several Danish reports on medical conditions in patients with schizophrenia , Munk-Jorgennsen et al (2000) found one study in which 70% of 399 acutely admitted psychiatric patients had medical problems (38% previously undiagnosed) and another in which 50% of 174 had somatic illnesses (31% previously undiagnosed) . • In a study of 110 state hospital patients with schizophrenia in USA , 38 (35%) had one or more medical condition (Parry & Barton 1988)

17. Morbidity • Jeste et al (1996) found that for unclear reasons, rheumatoid arthritis seems to occur only rarely in schizophrenia and CVS and DM may be increased in schizophrenia, although not unique to the illness, because affective disorders and other psychiatric illnesses may be also associated with increased risk. • Evaluating morbidity associated with schizophrenia is complicated by the lack of a uniform definition of morbidity, underreporting of physical illnesses by patients and medical providers and the role of medications in causing some of the physical illnesses ( Adler and Griffith 1991)

18. Autoimmune disorders • Ehrentheil(57) and Lipper and Werman(77) have noted a decreased incidence of asthma, hay fever, and other allergic reactions in schizophrenic patients. • Underdiagnosis has been proposed as one explanation for the negative association observed between schizophrenia and RA (Mors et al 1999) • Sabbah and Luce(1952) showed an alternating pattern of coexisting psychosis and allergies.

20. Smoking and Schizophrenia • Studies have shown that schizophrenic patients smoke cigarettes at almost double the rate of the general population. Reported prevalence rates of smoking range from 56% to 88% (Kelly&McCreadie 2000) • Schizophrenics tend to smoke high-tar cigarettes, inhale more deeply, and smoke for longer periods of time. • In the past cigarettes have been used in hospitals as rewards. • High rates of unemployment , decreased amount of social activities and general boredom may contribute to smoking in schizophrenia. • Some patients may use smoking as a form of self medication to relieve negative symptoms or even EPS.

21. Smoking • Research has suggested that nicotine’s interaction with dopamine may contribute to the smoking behaviour of schizophrenic patients. • Smokers are more likely to use drugs and alcohol than nonsmokers. Also smokers tend to be more sexually active which can lead to STD including HIV • People with schizophrenia who smoke require higher doses of neuroleptics than nonsmokers. Nicotine may increase the plasma clearance for some antipsychotic medications. It has also been demonstrated that smoking may reduce the effect of benzodiazepines.

22. Cancer • Increased and decreased prevalence for different types of cancer among schizophrenic populations have been reported in the literature. • Lower rates of lung cancer and higher rates of digestive and breast cancers • Brown et al (2000) found mortality rates for lung cancer in schizophrenic persons twice the expected values.

23. One study demonstrated that clozapine has been shown to contribute to a significant decrease in daily cigarette use in heavy smokers in comparison to typical neuroleptics.

25. Weight gain and Obesity • Overweight is defined by the WHO as a BMI of 25.0-29.9 and obesity as a BMI = to or > 30. Recent data estimate that more than 50% of US adults are overweight with 31% of men and 35% of women considered obese • In addition to the health care costs of obesity , social stigma, discrimination and low self -esteem are common problems among patients with obesity ( Myers and Rosen 1999) • Obesity can have serious effects on health and life expectancy through a number of disease processes including hypertension, coronary artery disease , type II diabetes and stroke.

26. Weight gain and Obesity • Using a BMI of 27 or higher Allison et al found that 42% of a group of individuals with schizophrenia compared to 27% of the general population. Obesity has been particularly severe for young schizophrenic women. • A waist size of 35 inches or more for women and 40 inches or more for men is associated with increased risks of high blood pressure, type II diabetes, dyslipidaemia, and metabolic syndrome • Clinicians should focus on preventing initial weight gain and obesity because subsequent weight loss is very difficult to achieve. FH of obesity and diabetes is important to note.

27. Possible Mechanism • In examining the binding profiles of antipsychotic agents, the receptor affinity characteristic most closely correlated with weight gain among novel antipsychotic medications was H1 antagonism (Wirshing et al 1999) . Although H1 blockade also causes sedation, the mechanism by which H1 receptor antagonism may increase weight is peripheral interference with normal satiety signals from the gut resulting in overeating. However what may contribute to the greater weight gain seen with some novel antipsychotics is the additional effect of 5-HT2c antagonism. It is known that compounds that stimulate 5-HT transmission reduce food consumption and cause weight loss.

28. Antipsychotic medications • Ziprasidone is associated with minimal risk, Risperidone with medium risk, Clozapine and Olanzapine with the greater risk. Data on Quetiapine have been variable but suggest that its weight gain liability is to be similar to that of Resperidone. Aripiprazole is claimed not to have any effect on weight ?. • The literature on weight gain with novel antipsychotics indicate that certain groups of patients, such as adolescents may be particularly susceptible to this problem. Theisen and colleagues reported that the prevalence of obesity in adolescent patients was 64% on clozapine and 56% on other atypicals ( olanzapine, risperidone ) compared with 30% on conventional antipsychotics and 28% for patients on no medications.

29. MarkedClozapine Olanzapine Zotepine Quetiapine Chlorpromazine Thioridazine Perphenazine Trifluperazine Moderate RisperidoneClopenthixol Sulpride Amisulpride Haloperidol Fluphenazine Flupenthixol Antipsychotics & Weight Gain(Zimmerman et al 2003)

30. No weight changeZiprasidone Weight lossMolindone Pimozide Low potential for weight changeAripiprazole Antipsychotics & Weight Gain

31. Impact of weight gain on treatment • Obese patients were 13 times as likely to request discontinuation of their current antipsychotic agent and 3 times as likely to be noncompliant with treatment compared with non-obese individuals (Weiden et al 2000, Kurzthaler&Fleischhacker 2001) • Patients should be weighed/measured at every visit for the first 6 months after medications initiation or change. • Interventions may include closer weight monitoring, engagement in a weight management programmes, use of an adjunctive treatment to reduce weight or even switching the medication to one with less weight gain liability.

33. Syndrome X 1-Dyslipidaemia 2-Type II Diabetes 3-Hypertension 4-Abdominal obesity 5-Insulin resistance or hyperinsulinaemia

34. In Henderson study, the rate of clozapine induced diabetes is 36.6%.

35. Diabetes and Schizophrenia • In the large national database of the Schizophrenia PORT study, 15% of participants reported having diabetes at some point in their lives and 11% reported having it currently. • Schizophrenia itself has been associated with insulin resistance and impaired glucose tolerance while antipsychotics often cause weight gain –all of which are associated with diabetes. Additionally some evidence suggests that new atypical drugs may contribute directly to hyperglycaemia. Furthermore tobacco use may interfere with glucose metabolism and sedentary isolated lifestyles and poor diet may increase diabetes risk.

36. Diabetes • Schizophrenic patients may be at a higher risk for developing diabetes than the population at large. This is type II diabetes which represents 90% of the cases. This high prevalence is related to the high prevalence of obesity. • Clozapine and Olanzapine are the agents most commonly associated with diabetes. One study followed patients who were taking clozapine for 5 years and found that 36.5% eventually received a diagnosis of type II diabetes. • Risperidone was not associated with significantly increased risk of diabetes.

37. Dr Hameedi of Yale School of Medicine ,Stamford, New York noted that even in treatment naïve schizophrenic patients, the risk of diabetes is two to four times that of people in the general population ( APA 2003)

38. Possible mechanism for diabetes • A link between diabetes and certain agents is supported by the finding that both clozapine and olanzapine may induce insulin resistance. • Some reports indicate a pattern of insulin resistance in schizophrenic patients independent of adverse medication effects ( Haupt and Newcomer 2001) • Atypical antipsychotics increase central adiposity or may cause direct effect on the glucose transporter function. • Another mechanism is the antagonism serotonin 5-HT1a receptors which may decrease pancreatic beta cell responsiveness to blood sugar levels.

39. American Diabetic Association • High risk for undiagnosed diabetes include: 1-BMI greater than 25 2-1st degree relative with diabetes 3-Habitual physical inactivity 4-Being a member of a high-risk ethnic population 5-Having delivered a baby heavier than 9lb or having gestational diabetes 6-Hypertension 7-HDL cholesterol level = 0r< 35md/dl or a triglyceride level = or > 250mg/dl 8-History of abnormal glucose tolerance test 9-History of vascular disease

40. Recommendations • Patients who have significant risk factors should have their fasting plasma glucose level or haemoglobin A1c value monitored 4 months after starting an antipsychotic and then yearly • Patients who are gaining weight should have the above measured every 4 months. • A baseline measure of blood sugar level should be collected for all patients before starting a new antipsychotic

42. What is the major cause of death in schizophrenia?

43. Cardiovascular illness & Hyperlipidaemia • A 10% increase in cholesterol level is associated with a 20%-30% increase in the risk of coronary heart disease. • Several retrospective reports reviewed by Meyer(40) and Wirshing(37) found elevations of lipids in patients who were taking newer antipsychotics. Early case reports focused on clozapine and found elevated levels of triglycerides but not elevated total cholesterol levels. • Patients with schizophrenia were found in one study to be less likely than other individuals to receive medications for lowering cholesterol.

44. The strongest data • UK study included 18309 schizophrenic patients , compared the odd ratios for developing hyperlipidaemia after receiving first and second generation antipsychotics. Patients who received olanzapine had significantly increased odds of developing hyperlipidaemia compared to patients who received no antipsychotic. • Risperidone was not associated with an increased risk in either comaprison • Clozapine and olanzapine are associated with increased triglyceride levels.

45. Possible mechanism • There is an association between the use of a diabenzodiazepine-derived atypical antipsychotic (i.e., clozapine, olanzapine, quetiapine) and profound effects on serum triglyceride levels. This association had emerged as early as 1986 with clinical studies of fluperlapine, a compound modelled on clozapine on which severe elevation of serum triglyceride were noted. Both risperidone and ziprasidone are nonbenzodiazepine atypical antipsychotics and as indicated appear to have minimal effects on serum lipids.

46. Risk factors for CVS illness 1-Obesity 2-Smoking, schizophrenic patients have a prevalence of smoking nearly twice that of the general population with estimates of 56%-88% in outpatient groups and 79% or more in chronic inpatient settings. 3-Hypertension 4-Diabetes 5-Lifestyle factors, lower levels of physical activity due to combined effects of sedating psychotropic medications and the core negative symptoms of the illness itself. 6-Hyperlipidaemia 7-Alcohol abuse

49. QT prolongation • Resting QTc is typically less than 420ms for males and 430ms for females with the risk for syncope or sudden death due to arrhythmia ( torsade de pointes, ventricular fibrillation ) increasing significantly for QTc greater than 500ms. • Prolongation of the QTc interval related to drug therapy is reversible on discontinuation of the offending agent. • QT interval becomes shorter as the heart rate becomes more rapid , the interval duration is usually corrected for heart rate and referred to as the QTc interval.

50. QTc prolongation and antipsychotics • Sertindole 22mesc • Ziprasidone 20.3mesc • Risperidone 11.6mesc • Olanzapine 6.8mesc • Quetiapine 14.5mesc • Thioridazine 35.6mesc • Haloperidol 4.7mesc • Aripiprazole no effect • Amisulpride no effect ?