Obesity, the Metabolic Syndrome and Schizophrenia

Patients with schizophrenia are at greater risk for obesity than other individuals due to factors including inactive lifestyle, poor dietary choices, and side effects of psychotropic medications.^[1] The metabolic effects of atypical antipsychotics have received particular attention in the literature as accrued experience demonstrates marked differences between various agents in their risk for weight gain and changes in serum triglycerides and glycemic control.^[2] The American Diabetes Association/American Psychiatric Association (ADA/APA) Consensus paper recognized that certain atypical antipsychotics are associated with greater metabolic dysfunction than others ( Table 1 ).^[3] Prospective data show mean weight increases during the first year of therapy of 11.7 to 13.9 lb for clozapine, and 15.0 to 26.0 lb for olanzapine, while risperidone and quetiapine showed mean gains of 4.4 to 5.1 lb and 6.1 to 12.3 lb, respectively.^[4] Ziprasidone and aripiprazole each showed weight gain of less than 2 lb.^[2,4]

Yet the correlation between obesity and schizophrenia, especially among female patients, antedates the availability of atypical antipsychotics. Allison and colleagues^[5] analyzed 1989 data on 150 individuals with schizophrenia from the 1989 National Health Interview Survey which showed that females with schizophrenia had significantly greater body mass index (BMI) compared with age-matched US norms from the same study (27.36 kg/m² vs. 24.50 kg/m² respectively, P < .001). There was also a trend toward greater obesity, which did not reach statistical significance among males with schizophrenia.^[5] Subsequent data for the years 1987 to 1996 (Figure) confirm the observation that obesity is equally prevalent among male schizophrenia patients and the general population, while females with schizophrenia are at greater risk for obesity.^[6]

Among the metabolic disorders, type 2 diabetes mellitus (DM) has received significant attention in the schizophrenia literature over the past 5 years for several reasons: (1) recent data confirming that DM is twice as prevalent among schizophrenia cohorts than in the general population^[7]; (2) the concern about glucose intolerance, DM, and diabetic ketoacidosis associated with atypical antipsychotic therapy culminating in FDA warnings and the recent ADA/APA consensus paper on this topic^[3]; and (3) changes in the third revision of the National Cholesterol Education Program's (NCEP) Adult Treatment Protocol (ATPIII) which elevated DM to a disorder equivalent to established coronary heart disease (CHD) in the 10-year risk for a major cardiovascular events.^[8] Another important feature of ATPIII was the renewed focus on the metabolic syndrome, a condition also known as syndrome X or the dysmetabolic syndrome.

As shown in Table 2 , the metabolic syndrome is defined by a cluster of clinical features, including increased visceral adiposity as measured by waist circumference, hyperglycemia, hypertension, and dyslipidemia.^[9] The metabolic syndrome is highly prevalent in the United States: The age-adjusted prevalence of metabolic syndrome from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 is 27.0%, with the lowest prevalence in the cohort ages 20-39 years (10.7% for men, 18.0% for women) and the highest in those ages 60 years and over (39.7% in men and 46.1% in women).^[9] This syndrome is of clinical concern because cross-sectional data from NHANES III showed the prevalence of coronary heart disease (CHD) to be significantly higher among nondiabetic patients with the metabolic syndrome (13.9%) than in diabetic patients who did not meet criteria for the syndrome (7.5%)^[10]; moreover, data from a large Scandinavian trial revealed that a diagnosis of the metabolic syndrome was associated with a 3-fold increased risk for both CHD and stroke.^[11] The metabolic syndrome also represents a prediabetic state which progresses over time to overt diabetes in a significant proportion of individuals. Evidence for this progression comes from NHANES III, which found that only 13% of diabetics did not meet criteria for the metabolic syndrome among the cohort over age 50 years.^[10]