Evidence-Based Perspective on Metabolic Syndrome and Use of Antipsychotics

Schizophrenia, a devastating mental illness that affects nearly 2.2 million Americans, is associated with high rates of morbidity and mortality.¹ Persons 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 an increased risk of cardiovascular morbidity and mortality.⁴ In fact, more than two-thirds of persons with schizophrenia die of coronary heart disease compared with approximately half in the general population.²

Metabolic syndrome is a global issue. Bobes and colleagues⁵ showed that prevalence of coronary heart disease and metabolic syndrome in Spanish patients with schizophrenia who were treated with antipsychotics was the same as that for persons in the general population who were 10 to 15 years older.⁵ In a study of 231 Turkish patients, Boke and colleagues⁶ found that 32% of persons with schizophrenia met criteria for metabolic syndrome, with a higher prevalence in women (61%) than in men (22.4%). It has been suggested that persons with schizophrenia may have a predisposition toward developing metabolic syndrome that is exacerbated by their generally sedentary lifestyle, poor dietary habits, limited access to care, poor insight, and medication-induced adverse effects.⁷

A number of studies have addressed some of the issues pertaining to the effect of metabolic abnormalities on overall quality of life. Weight gain and obesity increase the risk of impaired physical health and may lead to treatment nonadherence and decrements in subjective well-being.^8-10 Persons with schizophrenia and obesity have been found to have lower scores on measures of health-related quality of life.¹¹ These study findings have highlighted the deleterious effects of weight gain and its consequences on the long-term prognosis and life expectancy and underscore the need to develop methods to prevent and treat weight gain in this population.

In recent years, mental health care providers have been grappling with issues related to metabolic disturbance in schizophrenia as well as the adverse effects of antipsychotic treatments. Recent trials estimate that rates of obesity and diabetes in persons with schizophrenia are nearly twice those of the general population, and dyslipidemias are more common.¹² Prevalence of smoking is 3 times that seen in the general population. Taken together, these factors double the risk of cardiovascular morbidity and mortality compared with that of the general population.¹² A growing body of clinical and translational research evidence has implicated the use of atypical antipsychotics in causing and worsening weight gain, dyslipidemia, and diabetes,¹³ resulting in “an epidemic within an epidemic.”¹⁴

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study compared the incidence of metabolic syndrome in its sample population with an age-matched sample from the general population drawn from the National Health and Nutrition Examination Survey (NHANES).¹⁵ The prevalence of metabolic syndrome at baseline was higher among the CATIE study participants than among the NHANES sample. Among the CATIE study participants, overall prevalence of hypertension was 33.2%. The prevalence of diabetes was 10.4% for the entire cohort, increasing to 10.9% among persons with fasting blood 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, was found in 48.3% of all patients. Rates of non-treatment ranged from 30.2% for diabetes to 62.4% for hypertension and 88% for dyslipidemia.¹⁶ These data reiterate the dilemma confronting practitioners on how best to implement strategies that would change the long-term adverse health consequences of these conditions.

Metabolic Syndrome:
Is There Universal Consensus?
While metabolic syndrome is a growing concern for persons 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.¹⁷

Internal server error