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. The research project will address the impact of multi-class polypharmacy on the emerging epidemics of obesity and diabetes. Polypharmacy has been idenified as a source of rising health care costs and possible negative health consequences. Due in large part to increases in polypharmacy, spending on psychiatric medications in the Missouri Medicaid program has nearly doubled in the last 10 years, with similar increases reported nationwide. Despite largely unproven benefits, polypharmacy is associated with increased risk for medication interactions, poorer compliance, confounding of medication effects and can lead to further polypharmacy to treat side effects. The integrated research and training plan will develop the Applicant's expertise in the assessent of whole-body glucose and lipid metabolism and weight regulation in psychiatric patients receiving multi-class polypharmacy. Glucoregulatory abnormalities, diabetes, dyslipidemia, and increased adiposity have all been associated with antipsychotic treatment of schizophrenia. In addition, schizophrenia patients in clinical practice are commonly treated with multi-class polypharmacy, with up to 35% of atypical antipsychotic prescriptions accompanied by co-prescription of valproate, despite reports that the addition of valproate may further disturb glucose and lipid metabolism and weight regulation. Although sensitive methods are available, studies have not addressed the metabolic consequences of this common type of polypharmacy. This project aims to evaluate the effects of antipsychotic treatment in combination with valproate on glucose and lipid metabolism, abdominal fat, and total body fat using available gold standard methodologies that the Applicant requires instruction in.
The aims will be addressed in non-diabetic schizophrenia patients chronically treated with antipsychotics who will be randomized to receive either concomitant valproate versus no additional treatment. Relevant data are critically needed to target basic research, identify long-term cardiovascular risks, and plan therapeutic interventions.
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