This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Atypical antipsychotic medications have many potential benefits to patients with Schizophrenia and other chronic mental illnesses, but also carry the risk of significant weight gain and associated medical co-morbidity possibly related to altered glucose metabolism. Insulin resistance is thought to be the mechanism underlying potentially serious weight gain in patients already suffering from a major mental illness. It is believed that the oral hypoglycemic agent metformin (Glucophage) will counteract the insulin resistance caused by the antipsychotic medications clozapine (Clozaril) and olanzapine (Zyprexa), and thereby inhibit weight gain or promote weight loss in at risk patients. The purpose of this study is to compare the effectiveness of metformin in curtailing the weight gain caused by the atypical antipsychotic medications clozapine and olanzapine. The study design is a randomized, double-blind, 12 month clinical trial. The primary outcome variable to be evaluated is body weight. This outcome has high clinical relevance because it is disfiguring, causes significant distress, and compounds the social isolation often associated with psychotic disorders. Secondary outcome measures will be cardiovascular risk factors and measures of insulin resistance.
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