"Clinical Management of Metabolic Problems in Patients with Schizophrenia: Switching to Aripiprazole versus Continued Treatment with Olanzapine, Quetiapine, or Risperidone"

Metabolic abnormalities (e.g., elevated glucose, triglyceride and non-HDL cholesterol levels, decreased HDL cholesterol level, and elevated blood pressure) are associated with cardiovascular morbidity and premature mortality. All of these indicators of cardiovascular risk are more common in patients with schizophrenia than in matched controls. Although there is evidence suggesting that some patients with schizophrenia have intrinsic abnormalities in lipid and carbohydrate metabolism, some second-generation antipsychotics (i.e., clozapine, olanzapine, quetiapine, and risperidone) are associated with increased rates of metabolic abnormalities that predispose patients to cardiovascular disease (American Diabetes Association 2004).

The most appropriate treatment strategies for patients with schizophrenia and metabolic risk factors for cardiovascular disease have not been established. Switching patients who are taking an antipsychotic with a high liability for producing metabolic side effects to an antipsychotic with a low liability is a commonly chosen option with uncertain effectiveness. This is of particular interest when individuals with schizophrenia or schizoaffective disorder have had a good therapeutic response to an antipsychotic medication with a relatively high risk of metabolic side effects. The possible benefits of switching to a medicine with more advantageous metabolic effects must be weighed against the risk of clinical instability associated with changing treatment.

This study will enroll 300 individuals with schizophrenia or schizoaffective disorder, currently stabilized on treatment with olanzapine, quetiapine, or risperidone, who have increased risk for cardiovascular disease as indicated by body-mass index (BMI) > 27 and non-HDL cholesterol > 160 mg/dL. Subjects will be randomly assigned to switch to aripiprazole or to stay on their current medication. All subjects will receive a manualized behavioral intervention aimed at reducing their risk of cardiovascular disease.

Primary Aim: To compare the effects of switching to aripiprazole versus continued treatment with olanzapine, quetiapine, or risperidone on risk of cardiovascular disease as indicated by non-HDL cholesterol.

We hypothesize that individuals who switch to treatment with aripiprazole will have significantly larger decreases in non-HDL cholesterol levels compared to individuals who continue treatment with olanzapine, quetiapine, or risperidone.

Key Secondary Aim: To compare the effects of switching to aripiprazole versus continued treatment with olanzapine, quetiapine, or risperidone on the clinical stability of schizophrenic illness.