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Metabolic Syndrome and Mental Illness

John W. Newcomer, MD

Patients with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome and its components, risk factors for cardiovascular disease and type 2 diabetes. Although the prevalence of obesity and other risk factors such as hyperglycemia are increasing in the general population, patients with major mental illnesses have an increased prevalence of overweight and obesity, hyperglycemia, dyslipidemia, hypertension, and smoking, and substantially greater mortality, compared with the general population. Persons with major mental disorders lose 25 to 30 years of potential life in comparison with the general population, primarily due to premature cardiovascular mortality. The causes of increased cardiometabolic risk in this population can include nondisease-related factors such as poverty and reduced access to medical care, as well as adverse metabolic side effects associated with psychotropic medications, such as antipsychotic drugs. Individual antipsychotic medications are associated with well-defined risks of weight gain and related risks for adverse changes in glucose and lipid metabolism. Based on the medical risk profile of persons with major mental illnesses, and the evidence that certain medications can contribute to increased risk, screening and regular monitoring of metabolic parameters such as weight (body mass index), waist circumference, plasma glucose and lipids, and blood pressure are recommended to manage risk in this population. Treatment decisions should incorporate information about medical risk factors in general and cardiometabolic risk in particular. In addition to the implications for individual clinicians, the problem of disparity in meeting healthcare needs for persons with mental illness in comparison with the general population has become an important public policy concern, with recent recommendations from the National Association of State Mental Health Program Directors and the Institute of Medicine. This article provides an overview of cardiometabolic risk in patients with major mental illness and describes steps for risk reduction.

(Am J Manag Care. 2007;13:S170-S177)

Patients with major mental illnesses such as schizophrenia and bipolar disorder have increased risks of morbidity and mortality compared with the general population, with a 25- to 30-year shorter life span due primarily to premature cardiovascular disease (CVD) (eg, myocardial infarction [MI], stroke).1-4 Key modifiable risk factors that contribute to excess morbidity and mortality include cardiometabolic factors, such as overweight and obesity, dyslipidemia, diabetes, hypertension, and smoking.1-4 Although these risk factors are present within the general population,5 epidemiologic data suggest that patients with major mental illnesses have an increased prevalence of some or all of these risk factors.6 Treatment with psychotropic medications, including second-generation, or atypical, antipsychotic medications, can also be associated with adverse metabolic effects.7

This article provides an overview of cardiometabolic risk in patients with mental disorders such as schizophrenia and bipolar disorder, and associated increases in morbidity and mortality. Potential treatmentrelated effects are also discussed, along with considerations for managing risk.

Metabolic Syndrome: Definition and Risks Metabolic syndrome has been used to describe a grouping of cardiometabolic risk factors associated with insulin resistance, including8:

- Abdominal obesity
- Atherogenic dyslipidemia
- Elevated blood pressure (BP)
- Glucose intolerance
- Prothrombotic state
- Proinflammatory state

These metabolic risk factors are associated with the development of CVD, including coronary heart disease (CHD) and cerebrovascular disease, as well as type 2 diabetes mellitus (T2DM). Table 1 presents clinical criteria established by the National Cholesterol Education Program (NCEP) to define the metabolic syndrome.9

Abdominal obesity and related increases in insulin resistance are important factors that can contribute to excess morbidity and mortality.8 Obesity can lead to insulin resistance, or a reduced tissue sensitivity to insulin actions, which is associated with the development of other CVD risk factors, including dyslipidemia, prothrombotic and proinflammatory states, and diabetes.1,10,11 The association between increasing body mass index (BMI) and cardiovascular risk and mortality is well established.8-12 Central adiposity (ie, visceral abdominal adiposity) is particularly associated with insulin resistance12 and increased risk for T2DM and CVD.

Cardiometabolic Risk in Mental Illness: Morbidity and Mortality
The prevalence of cardiometabolic risk factors ishigher among patients with mental illness than in the general population.1,6 Most studies of metabolic syndrome or individual metabolic risk factors have been conducted in patients with schizophrenia or depression, but the evidence is consistent with more limited information for other serious mental disorders, such as bipolar disorder.6,13,14 Specifically, increased rates of insulin resistance and diabetes have been reported in association with schizophrenia and depression, including limited observations in unmedicated patients.14 Hypothesized contributing factors include smoking, poor nutrition, poverty, urbanization, and sedentary lifestyle,13 as well as adverse effects associated with psychotropic medications that include some of the second-generation antipsychotics (see Cardiometabolic Risk and Antipsychotic Agents below).7

Reduced access to medical care. Another potential contributor to the medical risk observed in mental health patients involves access to medical care. A review of community-based mental healthcare of patients with schizophrenia, major depression, dysthymia, bipolar disorder, anxiety disorder, panic disorder, obsessive-compulsive disorder, or alcohol abuse found significant limitations in the treatment of these patients.15 The reduced availability of healthcare services, combined with socioeconomic factors that make it difficult for some patients to work, retain healthcare insurance, and pursue care complicate the identification and treatment of comorbid medical conditions. In addition, specialization among healthcare professionals may result in reduced attention to overall medical health (ie, a psychiatrist may focus solely on treatment for bipolar disorder, but may not monitor for cardiometabolic risk factors).15

Cardiometabolic risk. Patients with mental illnesses such as schizophrenia and bipolar disorder have a higher prevalence of cardiometabolic risk factors compared with the general population. Obesity, hyperglycemia, smoking, and dyslipidemia are key modifiable risk factors for CVD and diabetes that are all more prevalent among patients with schizophrenia and bipolar illness.7

Impact of reduced primary and secondary prevention on mortality. Patients with major mental illnesses such as schizophrenia and bipolar disorder have a substantially higher risk of death compared with the general population. A study of Medicare patients admitted to the hospital for treatment of MI indicated that patients with comorbid mental illness of any type had an increased 1-year mortality rate of approximately 19%.16 Overall, the life expectancy of patients with major mental disorders is substantially shorter compared with the general population. An early study indicated that patients with schizophrenia had a 20% shorter life span compared with the general population.1 A more recent US study, however, indicated an even greater reduction in life span for those with major mental illness. This study examined age-adjusted death rates, standardized mortality ratios, and years of potential life lost for public mental health clients compared with the general population in 6 states over a period of several years. Patients with mental illness died at substantially younger ages than the general population. For those states in which both inpatient and outpatient data were available, the mean number of potential years of life lost for patients with major mental illnesses ranged from 25 to 30 years compared with the general population.2 CHD was the leading cause of death among patients with mental illness in all 6 states, similar to the ranking of heart disease in the general population for each state and for the United States as a whole, but with earlier cardiac death in the mentally ill.

Screening and Treatment Recommendations
Modifiable and nonmodifiable risk factors can contribute to overall cardiometabolic risk. It is important to assess modifiable risk factors in individual patients to evaluate patient risk of cardiovascular and metabolic diseases.1 The association between mental illness and increased cardiometabolic risk, particularly the association between psychiatric medications and risk, suggests a role for psychiatrists and other mental healthcare clinicians in monitoring risk and in assessing risk in relation to prescribing antipsychotic medications. Modifiable risk factors that should be evaluated at or near baseline and serially after prescription of antipsychotics include:

- weight
- waist circumference
- fasting plasma lipids (total, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol, and triglycerides)
- fasting and/or postload (or perhaps postprandial) plasma glucose
- BP

Patients who smoke should be instructed to quit and should be provided with support, including counseling and smoking cessation aids. Laboratory parameters should be monitored periodically, paying particular attention to changes in any value after initiation of a new antipsychotic agent.1

Weight gain associated with atypical antipsychotic agents generally occurs within the first few months after initiation and may not stabilize for more than a year.6 The American Diabetes Association (ADA) recommends weight monitoring at 4, 8, and 12 weeks after initiating a change in antipsychotic therapy, and quarterly thereafter. A weight gain of >5% of baseline weight may signal the need to switch to a different atypical antipsychotic agent. In addition to monitoring by physicians, patients should be encouraged to track their own weight and waist circumference.6

Similar recommendations for weight, glucose, and lipid monitoring come from the Mount Sinai Conference, which brought together psychiatrists, endocrinologists, and other medical experts to develop guidelines for the routine monitoring of adult schizophrenia patients receiving antipsychotic therapy.17 These guidelines do, notably, recommend that patients with schizophrenia should be considered at high risk for CHD. Therefore, based on the NCEP guidelines, their lipid profile might need to be monitored more frequently (ie, every 2 years for normal LDL-C levels, and every 6 months for LDL-C >130 mg/dL) than is recommended by the ADA/American Psychiatric Association consensus statement. The Mount Sinai guidelines suggest that fasting glucose or glycated hemoglobin (A1C) could be used for glucose monitoring, whereas the ADA recommendations for screening in the general population advise against the use of A1C because of its relative insensitivity as a screening measure.

The introduction of regular routine monitoring should allow for the early detection of changes in these important risk factors, and so improve the overall long-term health of patients with schizophrenia and other mental illnesses.

Confirmed laboratory values that exceed defined criteria (Table 1) should result in intervention, including therapeutic lifestyle change, consideration of changes in potentially contributory psychotropic medications, and referral to a primary care provider or an appropriate specialist. Coordination of care between psychiatric and primary care providers is essential under these circumstances. After measurement at or near baseline, fasting plasma glucose, lipid levels, and BP should be assessed at least 3 months after initiation of antipsychotic medication. Thereafter, quarterly measurement of weight and annual monitoring of plasma glucose, lipid levels, and BP is recommended.6 Patients who develop abnormal glucose and lipid profiles should be evaluated promptly, even if no symptoms are noted.

Access to Care
Patients with major mental illnesses should enjoy access to medical care similar to persons in the general population, but there is strong evidence of disparities in the level of healthcare provided to persons with mental illnesses compared with the general population. The World Health Organization has suggested that persons with mental disorders have a right to healthcare comparable to that received by the general population.18 Recent wellcontrolled studies indicate, however, that persons with mental illnesses receive reduced levels of healthcare.19 In addition to reductions in primary prevention,16 persons with mental health conditions receive less secondary care.19

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