Aggressive Treatment of Metabolic Syndrome in Patients Treated With Clozapine for Schizophrenia

Background

Compared with the general population, patients with schizophrenia have an increased risk of death from atherosclerotic cardiovascular diseases (ASCVD) that reflect coronary heart disease, stroke and peripheral vascular disease (Newcomer, 2007). Among the factors contributing to the increased prevalence of ASCVD in schizophrenia are a) unhealthy lifestyle (cigarette smoking, lack of physical activity, increased consumption of calorie-dense foods rich in saturated fats and carbohydrates), b) genetic vulnerability to glucose intolerance and diabetes; c) metabolic side-effects of psychotropic drugs; and d) lack of access or compliance with community-based medical care, particularly clozapine or olanzapine. Biologically, the common pathway leading to increased risk of ASCVD in schizophrenia is the metabolic syndrome, an entity defined as 3 or more of the following 5 characteristics: abdominal obesity, increased blood pressure, increased fasting glucose, increased levels of triglycerides and abnormally low levels of high-density lipoprotein cholesterol. The prevalence of metabolic syndrome in schizophrenia ranges form 29% to 63% and is significantly greater than the frequency of 21% in the general population (Correll et al., 2006). As in the general population, the metabolic syndrome of patients with schizophrenia is explained by increased intraabdominal adiposity leading to insulin resistance and excess of circulating free fatty acids which are converted into triglyceride-rich lipoproteins with atherogenic potential.

The treatment of metabolic syndrome relies primarily on therapeutic lifestyle changes aiming to reduce weight, decrease intake of saturated fats and carbohydrates with high glycemic index, eliminate smoking, and increase physical activity. Drug therapy is required for the patients who fail to respond to lifestyle changes and the American Heart Association (AHA) has published detailed guidelines for the pharmacologic management of metabolic syndrome (Grundy et al., 2005). These guidelines are based on research indicating substantial improvement in the risk of ASCVD of patients with metabolic syndrome treated with metformin and acarbose for impaired glucose tolerance; statins, fibrates and nicotinic acid for lipid abnormalities; angiotensin receptor blockers for increased blood pressure; and sibutramine and orlistat for weight management. Some of these interventions (e.g., metformin and sibutramine for weight management) have been completed in research settings with small samples of patients with schizophrenia (Henderson et al., 2005; Wu et al., 2008) and have produced promising results. However, treatment trials using the comprehensive AHA guidelines have not yet been conducted in schizophrenics with metabolic syndrome.

Current Standard of Care at Zucker Hillside Hospital

The Aftercare Clinic at Zucker Hillside Hospital has the oldest Clozapine Clinic in the U.S. Opened in 1987, the Clozapine Clinic has a current enrollment of 230 adult patients. According to hospital policy, all Clozapine Clinic patients must have an annual physical evaluation and laboratory tests for the detection of obesity, dyslipidemia, glucose intolerance, hypertension and metabolic syndrome. The mandatory physical examinations are performed by each patient's outside physician or by the Clinic's Nurse Practitioners. Laboratory testing is performed at Long Island Jewish Medical Center's laboratories. The physical examinations and laboratory findings are reviewed by each patient's psychiatrists. Patients with physical or laboratory abnormalities are referred for care to internal medicine specialists (i.e., general internal medicine, endocrinology, cardiology) in private practice or to the appropriate outpatient clinics at Long Island Jewish Medical Center as deemed necessary by their psychiatrists. At the present time, it is not known how many schizophrenia patients with metabolic syndrome treated in the Aftercare Program (outpatient clinic) at ZHH receive care according to the standard defined by the American Heart Association.