Comparison of Antipsychotics for Metabolic Problems in Schizophrenia or Schizoaffective Disorder

Metabolic abnormalities associated with cardiovascular morbidity and premature mortality are
more common in patients with schizophrenia than in matched controls. Although there is some
evidence that patients with schizophrenia have intrinsic abnormalities in lipid and
carbohydrate metabolism, some antipsychotics (i.e., clozapine, olanzapine, quetiapine, and
risperidone) are associated with increased rates of metabolic abnormalities that predispose
patients to cardiovascular disease.

This is an investigator-initiated clinical trial that will be conducted at 30 research sites
that are a part of the NIMH Schizophrenia Trials Network.

The aims of the study are to (1) determine the relative effects of switching to
aripiprazole, versus continued treatment with olanzapine, quetiapine, or risperidone, on
metabolic parameters associated with cardiovascular disease, and (2) to determine the
effects of switching to aripiprazole versus continued treatment with olanzapine, quetiapine,
or risperidone on the clinical stability of schizophrenic illness.

This study design is a multi-site, single-blind (rater) randomized controlled trial of 300
patients with schizophrenia or schizoaffective disorder comparing treatment with the
following medications: olanzapine, quetiapine, risperidone, and aripiprazole. The study will
enroll patients with schizophrenia or schizoaffective disorder for whom a medication change
may be indicated because of an increased risk of cardiovascular disease in spite of adequate
control of symptoms on their current antipsychotic medication. Patients who are taking
olanzapine, quetiapine, or risperidone and who have a body-mass index (BMI) greater than or
equal to 27 and non-HDL cholesterol greater than or equal to 130 mg/dl will be eligible (if
non-HDL is between 130-139mg/dL, LDL cholesterol must be greater than 100mg/dL). All
treatments will be open label. Raters will be blinded to treatment assignment. Patients will
be followed for up to 6 months.

Inclusion Criteria:

- Diagnosed with schizophrenia or schizoaffective disorder

- Currently treated with olanzapine, quetiapine or risperidone

- BMI greater than or equal to 27

- Non-HDL cholesterol greater than or equal to 130 mg/dL (if non-HDL cholesterol is
between 130 - 139 mg/dL, then LDL cholesterol must be greater than 100 mg/dL).

Exclusion Criteria:

- Diabetes (FBS greater than or equal to 126) or treatment with oral hypoglycemic drug
or insulin

- Non-HDL cholesterol greater than 300 mg/dL

- Serum triglycerides greater than 500 mg/dL

- Patients in the first episode of schizophrenia or schizoaffective disorder

- Known hypersensitivity to aripiprazole

- On weight loss medications