Comparison of Antipsychotics for Metabolic Problems in Schizophrenia or Schizoaffective Disorder

Study Overview
=================
Brief Summary
-----------------
The study will compare the effectiveness of antipsychotic medications for patients with schizophrenia or schizoaffective disorder for whom a medication change may be indicated because of an increased risk of cardiovascular disease.

Detailed Description
-----------------
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.

Official Title
-----------------
Clinical Management of Metabolic Problems in Patients With Schizophrenia

Conditions
-----------------
Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
-----------------
* Drug: Risperidone
* Drug: Olanzapine
* Drug: Quetiapine
* Drug: Aripiprazole


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will switch to aripiprazole with a cross-titration from the current antipsychotic over 3-4 weeks. Allowed final dosage range for aripiprazole was 5-30 mg/day | Drug: Aripiprazole<br>* Switching medication to aripiprazole for schizophrenia for up to 6 months in study<br>* Other names: Abilify;|
| Active Comparator: 2<br>Participants will continue with their current antipsychotic treatment, either olanzapine 5-20 mg/day, quetiapine 200-1200 mg/day, or risperidone 1-16 mg/day. | Drug: Risperidone<br>* Continued treatment with the medication risperidone for schizophrenia for up to 6 months in study<br>* Other names: Risperdal;Drug: Olanzapine<br>* Continued treatment with the medication olanzapine for schizophrenia for up to 6 months in study<br>* Other names: Zyprexa;Drug: Quetiapine<br>* Continued treatment with the medication quetiapine for schizophrenia for up to 6 months in study<br>* Other names: Seroquel;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Non-HDL Cholesterol Level for Patients Assigned to Stay and Patients Assigned to Switch Over 24 Weeks | Change in non-HDL cholesterol measured at baseline and every 4 weeks for 24 weeks. The efficacy analysis corresponded to a comparison of change in non-HDL cholesterol from baseline to 24 weeks between treatment groups (stay versus switch). Repeated measurements mixed effects linear models were fit for the primary analysis. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Failure, Defined as Psychiatric Hospitalization, a 25 Percent Increase From Baseline on the Positive and Negative Syndrome Scale or Substantial Clinical Deterioration on the Clinical Global Impressions-Change (CGI-C) |  | Measured at Month 6 |