Metabolic Syndrome Risk Doubles With Schizophrenia Drug

ROCHESTER, N.Y., July 11 -- Patients taking the antipsychotic Clozaril (clozapine) for schizophrenia need to be monitored for signs of metabolic syndrome, according to investigators here.

In a study evaluating patients with schizophrenia or schizoaffective disorder taking Clozaril, more than half had metabolic syndrome symptoms, compared with only one-fifth of matched controls, said psychiatrist J. Steven Lamberti, M.D., of the University of Rochester (N.Y.) Medical Center.

"This study suggests that patients who need the most effective medication are between a rock and a hard place," Dr. Lamberti and colleagues reported in the July issue of the American Journal of Psychiatry.

Clozaril and other atypical antipsychotic agents have previously been associated with metabolic abnormalities, but this study is the first controlled look at the prevalence of the syndrome in patients taking Clozaril, the investigators said.

"People with schizophrenia are known to exercise less and have poor diets," Dr. Lamberti said. "Those factors contribute to metabolic syndrome. We can't say how much clozapine contributes to metabolic syndrome, but we have shown the high prevalence of the syndrome in those who take clozapine."

For the study, the investigators used National Cholesterol Education Program and American Diabetes Association criteria for defining metabolic syndrome.

Patients were considered to have metabolic syndrome if they had three or more of the following criteria:

•Waist circumference >102 cm for men and >88 cm for women
•Fasting blood triglyceride level ≥150 mg/dl
•HDL <40 mg/dl for men and <50 mg/dl for women
•Blood pressure ≥130 mm Hg systolic or ≥ 85 mm Hg diastolic
•Fasting blood glucose level ≥100 mg/dl.

They looked at 93 patients with schizophrenia or schizoaffective disorder who had been taking Clozaril for at least six months, and compared them with 2,701 controls selected from the National Health and Nutrition Examination Survey (NHANES).

The patients were matched by age (between 17 and 55 years old), body mass index ≥19 kg/ m², and race/ethnicity (white, African American, Hispanic American, or "other").

The authors used logistic regression analysis to see whether factors other than Clozaril might account for differences in the prevalence of the metabolic syndrome.

They found that 50 of the patients taking Clozaril (53.8%) met the criteria for the metabolic syndrome, compared with 369 (20.7%) of controls.

Among the patients taking Clozaril, they also found significant associations were between the presence of metabolic syndrome and both age (P<0.001) and body mass index (P<0.0001), and a "marginally significant" association between the syndrome and the duration of Clozaril therapy (P=0.06). They did not find any associations between other medications, smoking, or other clinical or demographic variables.

Among the controls, metabolic syndrome was significantly associated with age, race/ethnicity, family history, and BMI (P for race=0.02; for all others, P<0.0001).

The authors noted that the medical risks of Clozaril therapy need to be balanced with its demonstrated benefit for patients with refractory schizophrenia, and call for better medical supervision of patients who are taking the drug.

"Many adults with schizophrenia receive little or no medical care," they wrote. "Such care is important, given the risk of metabolic abnormalities associated with schizophrenia itself and with antipsychotic medications in general."

They concluded, "In response to these issues, current schizophrenia treatment guidelines recommend regular monitoring of body mass index, lipid levels, fasting blood glucose levels, and blood pressure. Regular monitoring may be especially critical for patients taking clozapine, given the high prevalence of metabolic abnormalities reported in this study and others."

The authors noted several limitations of the study. "Despite the high prevalence rate noted in this study, the study did not allow determination of the degree to which clozapine was responsible," they wrote. "Study limitations include the lack of a nonmedicated schizophrenia control group, a lack of random assignment, and a lack of longitudinal follow-up."