Schizophrenia, Metabolic Syndrome, and Antipsychotics

Sponsored by CME LLC for 1.5 Category 1 credits.
Original release date 03/08. Approved for CME credit through February 2009.

Educational Objectives

After reading this article, you will be familiar with:

     • What constitutes metabolic syndrome.
     • Why patients with schizophrenia are at increased risk for metabolic syndrome.
     • How to manage metabolic syndrome in patients with schizophrenia.


Who will benefit from reading this article?

Psychiatrists, primary care physicians, neurologists, nurse practitioners, and other health care professionals. Continuing medical education credit is available for most specialists. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing board.

Dr Narasimhan is professor of psychiatry and director of biological research, Office of Biological Research in the department of neuropsychiatry and behavioral science at the University of South Carolina School of Medicine in Columbia. She reports that she has received a grant and/or research support from AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, and Janssen; she is on the speaker's bureau of Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen; and she is on the advisory boards of Bristol-Myers Squibb and Eli Lilly.

Ms Bailey is a third-year medical student at the University of South Carolina School of Medicine. She reports no conflicts of interest concerning the subject matter of this article.

Schizophrenia, a devastating mental illness that affects nearly 2.2 million Americans, is associated with high rates of morbidity and mortality.¹ Individuals with schizophrenia have a 20% shorter life expectancy than the general population.^1,2 Furthermore, among persons with schizophrenia, there is an increased prevalence of metabolic syndrome characterized by a constellation of risk factors, including insulin resistance, abdominal obesity, dyslipidemia, hyperglycemia, and hypertension,³ all of which contribute to the risk of cardiovascular morbidity and mortality.⁴ In fact, more than two thirds of patients with schizophrenia, compared with approximately half of the general population, die of coronary heart disease.²

In addition, metabolic syndrome is a global issue. Bobes and colleagues⁵ showed that the prevalence of coronary heart disease and metabolic syndrome in Spanish patients with schizophrenia who were treated with antipsychotics was the same as that in persons from the general population who were 10 to 15 years older.⁵ It has been suggested that patients with schizophrenia may have an inherent predisposition toward metabolic syndrome that is further complicated by their sedentary lifestyle, poor dietary habits, lack of access to care, poor insight, and medication-induced adverse effects.⁶

A number of studies have addressed some of the issues pertaining to the impact of metabolic abnormalities on overall quality of life. Weight gain and obesityincrease the risk of impaired physical health and may lead to nonadherence and decrements in subjective well-being.^7-9 These studies have highlighted the deleterious effects of weight gain and its consequences on the long-term prognosis and life expectancy of patients with schizophrenia, and they emphasize the need to evaluate methods to prevent and treat weight gain in this population.

In recent years, mental health providers have been grappling with issues pertaining to metabolic disturbance in schizophrenia as well as the adverse effects of antipsychotic treatments. Recent trials estimate that rates of obesity and diabetes in those with schizophrenia are nearly twice that in the general population, and dyslipidemias are more common.¹⁰ The prevalence of smoking is 3 times that seen in the general population. These risks translate into cardiovascular morbidity and mortality with a risk twice that of the general population.¹⁰ A growing body of clinical and translational research evidence has implicated atypical antipsychotics in causing and worsening weight gain, dyslipidemia, and diabetes,¹¹ resulting in "an epidemic within an epidemic."¹²

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, one of the largest studies of schizophrenia to date, compared metabolic syndrome in its sample with an age-matched sample from the general population drawn from the National Health and Nutrition Examination Survey (NHANES).¹³ The prevalence of metabolic syndrome at baseline was higher in the CATIE participants than in the NHANES participants. In the CATIE study, the overall prevalence of hypertension was 33.2%. The prevalence of diabetes was 10.4% for the entire cohort, with a prevalence of 10.9% in patients with fasting glucose results obtained 8 hours or more after their last meal. Dyslipidemia, as defined by elevated serum triglyceride levels, was found in 47.3% of fasting patients and when defined as low serum levels of high-density lipoprotein (HDL) cholesterol, it was found in 48.3% of all patients. Rates of nontreatment ranged from 30.2% for diabetes to 62.4% for hypertension and 88.0% for dyslip- idemia.¹⁴ These data reiterate the dilemma confronting practitioners in clinical practice on how best to determine strategies that would change the long-term adverse health consequences of these conditions.

Metabolic syndrome: do we have a universal consensus?

While metabolic syndrome is a growing concern for patients with mental illness, there is no universal agreement on precisely what metabolic syndrome is or how to concisely define it, thus making the diagnosis of metabolic syndrome an ambiguous task. Controversies stem from guidelines with different diagnostic criteria and debate over whether the syndrome represents anything more than the risk associated with these individual abnormalities.¹⁵

Metabolic syndrome is defined as a cluster of clinical and laboratory test result abnormalities including abdominal obesity, insulin resistance, hypertension, low levels of HDL cholesterol, and high levels of triglycerides—all of which can pose significant risk for cardiovascular morbidity and mortality.⁴ The most recent definitions come from the International Classification of Diseases-9th revision, the International Diabetes Federation (IDF), the World Health Organization (WHO), the American Heart Association, the American Diabetes Association, the NIH, and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The most commonly applied definitions are from the WHO, the NCEP ATP III, and the IDF, and each includes slightly varying criteria (Table 1).^16-18

Risk factors such as abdominal obesity, fasting triglyceride levels, HDL cholesterol levels, blood pressure, and fasting glucose levels are included in the criteria when diagnosing metabolic syndrome.^16-18 Other important and potentially modifiable risk factors may also warrant consideration, including elevated levels of low-density lipoprotein (LDL) cholesterol, family history of premature coronary heart disease (age 45 years or youn- ger for men and 55 years or younger for women), ethnicity, postmenopausal status, cigarette smoking, diet, alcohol consumption, and exercise or lack of activity either with or without weight changes.¹³

While the current definitions seem to imply that the different components of metabolic syndrome are equal in importance, analyses of the components of metabolic syndrome have shown that the individual components are not necessarily equally associated with the risk for coronary heart disease.¹³ In fact, most of the risk associated with metabolic syndrome is linked with age, blood pressure, diabetes, and HDL cholesterol.¹³ Therefore, the burden of diagnosis is placed on the physician, who must closely monitor patients who are taking antipsychotics, especially atypical antipsychotics.