Ziprasidone for Improving Insulin Sensitivity in People With Schizophrenia Who Are at Risk for Diabetes

People with schizophrenia often lead more sedentary lifestyles than people without the
disease, and they are frequently treated with antipsychotic medications that cause weight
gain. Combined, these factors produce an increased risk for metabolic syndrome, which can
lead to heart disease and type 2 diabetes. Characteristics of metabolic syndrome include
carrying excess weight around the abdominal region; high blood pressure; high blood sugar
levels; high levels of fat in the blood; and low levels of HDL cholesterol. Recent studies
have shown that certain atypical antipsychotic drugs are relatively weight-neutral. Switching
from a drug that promotes weight gain to a weight-neutral medication, such as ziprasidone,
may result in significant weight loss. There is insufficient evidence, however, demonstrating
the extent of improvement in insulin sensitivity after switching medications. This study will
evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical
antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage
in people with schizophrenia who are at risk for diabetes.

Participants in this open label study will currently be undergoing treatment with risperidone
or olanzapine at the time of study entry. Upon study entry, they will be randomly assigned to
either switch to ziprasidone treatment or remain on their current medications. Both groups
will be treated for 26 weeks. Participants will report to the study site for evaluations
biweekly until week 10 and then monthly for the duration of the study. The following outcomes
will be assessed at study entry and Week 26: insulin sensitivity, using an intravenous
glucose tolerance test; visceral fat mass, using a CT scan; and total adiposity, using a
dexascan.

Inclusion Criteria:

- Diagnosis of schizophrenia or schizoaffective disorder

- Currently receiving antipsychotic therapy with risperidone or olanzapine

- Overweight

Exclusion Criteria:

- Diagnosis of diabetes

- Hospitalization for schizophrenia or schizoaffective disorder within 90 days prior to
study entry

- Refractory schizophrenia or schizoaffective disorder

- Currently receiving therapy with clozapine

- No stable residence and phone number for 90 days prior to study entry

- Prior unsuccessful treatment with ziprasidone

- Intolerance to ziprasidone