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Physical Health Of Patients With Schizophrenia. Dr. Ahmed Shoka Consultant Psychiatrist. Schizophrenia. Strikes one in a hundred And affects many more. The Mission. Facts Figures Findings Challenge Implication. The Concept.

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physical health of patients with schizophrenia

Physical Health Of PatientsWith Schizophrenia

Dr. Ahmed Shoka

Consultant Psychiatrist

schizophrenia

Schizophrenia

Strikes one in a hundred And affects many more.

the mission
The Mission
  • Facts
  • Figures
  • Findings
  • Challenge
  • Implication
the concept
The Concept
  • Physical medicine is becoming more psychological and Psychiatry is becoming more biological ( Physical) ?
physical examination
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.
alarming figures
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.
koranyi ek 1979
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
introduction
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.
excessive mortality and morbidity
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
remember
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 )
morbidity
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)
morbidity17
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)
autoimmune disorders
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.
smoking and schizophrenia
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.
smoking
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.
cancer
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.
slide23

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.

weight gain and obesity
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.
weight gain and obesity26
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.
possible mechanism
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.
antipsychotic medications
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.
antipsychotics weight gain zimmerman et al 2003
MarkedClozapine Olanzapine Zotepine Quetiapine Chlorpromazine Thioridazine Perphenazine Trifluperazine

Moderate RisperidoneClopenthixol Sulpride Amisulpride Haloperidol Fluphenazine Flupenthixol

Antipsychotics & Weight Gain(Zimmerman et al 2003)
antipsychotics weight gain
No weight changeZiprasidone

Weight lossMolindone Pimozide

Low potential for weight changeAripiprazole

Antipsychotics & Weight Gain
impact of weight gain on treatment
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.
syndrome x
Syndrome X

1-Dyslipidaemia

2-Type II Diabetes

3-Hypertension

4-Abdominal obesity

5-Insulin resistance or hyperinsulinaemia

diabetes and schizophrenia
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.
diabetes
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.
slide37

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)

possible mechanism for diabetes
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.
american diabetic association
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

recommendations
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
cardiovascular illness hyperlipidaemia
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.
the strongest data
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.
possible mechanism45
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.
risk factors for cvs illness
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

qt prolongation
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.
qtc prolongation and antipsychotics
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 ?
maudsley guidelines for qtc
Maudsley Guidelines For QTc
  • QTc < 440ms (men) or < 470 (women)

No action required unless abnormal T-wave morphology.

  • QTc > 440ms (men) or 470ms (women) but < 500ms

Consider switch to drug of lower effect, perform ECG and consider referral to cardiologist.

  • QTc > 500ms
  • Stop suspected causative drug(s) and switch to drug of lower effect, refer to cardiologist immediately.
  • Abnormal T-wave morphology

Review treatment . Consider switch to drug of lower effect. Refer to cardiologist immediately.

recommendations52
Recommendations
  • Schizophrenic patients should be considered to be at high risk for coronary heart disease. As a result lipid screening should be carried out at least every 2 years when LDL is normal and every 6 months when the LDL level is greater than 130mg/dl
  • If LDL is greater than 130mg/dl the mental health care provider should refer the patient to a primary care provider or an internist .
  • Baseline ECG is needed before initiation treatment with ziprasidone. A subsequent ECG is indicated if the patient presents with symptoms associated with a prolonged QT interval (e.g., syncope).
idf consensus definition of the metabolic syndrome
IDF consensus definition of the Metabolic Syndrome
  • Central obesity: waist circumference >94cm for Europid men and >80cm for Europid women
  • Plus any two of the following four factors: *raised TG level: >150mg/dL(1.7 mmol/L) or specific treatment for this lipid abnormality *reduced HDL cholesterol :<40 mg/dL (1.03 mmoI/L) in males and <50 mg/dL(1.29 mmoI/L) in females or specific treatment for this lipid abnormality *raised blood pressure:systolic BP > 130 or diastolic > 85 mm hg or treatment of diagnosed hypertension * raised fasting plasma glucose : >100 (5.6 mmoI/L) or previously diagnosed type II diabetes If above 5.6 mmoI/L GTT is strongly recommended but is not necessary to define presence of the syndrome.
myocarditis in patients taking clozapine
Myocarditis in patients taking clozapine
  • Case reports indicate that clozapine is associated with a risk of fatal myocarditis. Seven cases with one fatality among 15600 patients were reported in Canada and 30 cases with eight fatalities among 24108 patients were reported in UK.
  • Symptoms of myocarditis include unexplained fatigue, dyspnoea, tachypnoea, fever, chest pain, palpitations. 80% of cases of myocarditis occurred within 6 weeks of the patient’s starting clozapine. The mortality rate from myocarditis approaches 40%.
  • If suspected, measure patient’s white cell count and plasma level of troponin.
elevated prolactin levels
Elevated Prolactin levels
  • Antipsychotic medications particularly first generation agents and risperidone can cause hyperprolactinaemia by their activity at dopamine D2 receptors.
  • Estimates of the prevalence of menstrual disturbances associated with antipsychotic use vary from 15% to 91% in different studies.
  • Hyperprolactinaemia impairs sexual function by inhibiting gonadotropin-releasing hormone by means of a short feedback loop between the pituitary and hypothalamus.
  • Sexual dysfunction is a major cause for non compliance.
  • Women are more sensitive than men to the effects of antipsychotics on prolactin.
osteoporosis
Osteoporosis
  • Both male and female schizophrenic patients have a high prevalence of osteoporosis.
  • Several mechanisms may explain that risk; direct effect of hyperprolactinaemia, effects of chronic low oestrogen or testosterone and other lifestyle factors including smoking, alcohol abuse, poor diet, lack of sun exposure, and polydipsia.
  • Osteoporosis is associated with significant morbidity and mortality.
potential risk factors for osteoporosis
Potential risk factors for osteoporosis
  • Factors due to schizophrenia itselfPoor diet Limited weight-bearing exercise Smoking ( has a direct toxic effect on osteoblasts)
  • Factors due to antipsychotic treatmentHyperprolactinaemia Secondary lowered oestrogen Secondary lowered testosterone
cataract
Cataract
  • Visual impairment is greater when cataract is situated more posteriorly .
  • Phenothiazines have been found to increase the risk of developing cataract mostly anterior subcapsular and therefore less likely to impair vision.
  • Data from animal studies suggest that quetiapine might be associated with cataract development.
  • Schizophrenic patients have other risk factors for lens opacities as diabetes, hypertension, and poor nutrition.
polydipsia
Polydipsia
  • Polydipsic patients consume large amounts of liquids , in excess of 3 litres per day and in some cases massive quantities such as 10-15 litres per day.
  • Caucasians and males may have a greater likelihood of being polydipsic .
  • Studies suggest that polydipsia among schizophrenic patients is underestimated.Up to 20% of chronic patients
  • Goldman and Blake suggested that hippocampal dysfunction may be important given its regulation of vasopressin and thirst.
  • Polydipsia may be linked to dopamine supersensitivity perhaps explaining why people with TD have a greater risk .
polydipsia62
Polydipsia
  • Clozapine has also been tried as a treatment for polydipsia. This is possibly explained by research finding that the moderate D1 blockade has been linked to a decrease in water consumption in animals.
  • Polydipsia ( water intoxication) can lead to kidney problems and osteoporosis. Water intoxication occurs when low serum sodium levels lead to brain oedema causing neurological and psychiatric symptoms such as nausea, vomiting, ataxia, seizures, coma, intensified psychosis , agitation and irritability.
conclusion
Conclusion
  • Schizophrenia is now fully recognised as a multi-dimensional illness with profound impact on behaviour, perceptions, thinking, emotions, neurocognition, psychosocial functioning, quality of life and physical health.
  • Ranking high among the causes of poor physical health in schizophrenic patients are the unhealthy lifestyle practices so prevalent in this disorder. 70%-80% of schizophrenic patients are chronic smokers ( Davidson et al 2001). High % of those patients have sedentary habits and poor dietary choices( Brown et al 1999, Davidson et al 2001). Co-morbid substance use have been shown to be common and further contribute to poor physical health and less frequent medical follow-up.
the challenge

The Challenge

To ensure that the physical health of patients with schizophrenia is given the priority it deserves, helping them to face their future with the lowest possible morbidity and mortality odds stacked against them.

my next topic for discussion
My Next Topic For Discussion
  • Gender Differences in the Prescribing of Antipsychotic Drugs highlighting the conclusion that optimal maintenance regimens of antipsychotics for women and men are not the same.
  • Another exciting prospect !!
vision statement
Vision Statement
  • State the vision and long term direction
goal and objective
Goal and Objective
  • State the desired goal
  • State the desired objective
  • Use multiple points if necessary
today s situation
Today’s Situation
  • Summary of the current situation
  • Use brief bullets, discuss details verbally
how did we get here
How Did We Get Here?
  • Any relevant historical information
  • Original assumptions that are no longer valid
available options
Available Options
  • State the alternative strategies
  • List advantages & disadvantages of each
  • State cost of each option
recommendation
Recommendation
  • Recommend one or more of the strategies
  • Summarize the results if things go as proposed
  • What to do next
  • Identify action items