Determining Metabolic Effects of Valproate and Antipsychotic Therapy

• Oral glucose tolerance test (fsOGTT) and hyperinsulinemic pancreatic clamp [ Time Frame: Measured at baseline and Weeks 6 and 12 ] [ Designated as safety issue: No ]
  

• Body composition using dual energy x-ray absorptiometry, magnetic resonance scans, and anthropomorphic measurements [ Time Frame: Measured at baseline and Weeks 6 and 12 ] [ Designated as safety issue: No ]
  

This project aims to study the whole-body metabolic processes responsible for hyperglycemia, dyslipidemia and increased adiposity in schizophrenia patients treated with antipsychotic medications in combination with valproate. The project hypothesizes that combined treatment with valproate and antipsychotic medications will decrease insulin sensitivity at the level of skeletal muscle, liver and adipose tissue, in comparison to antipsychotic monotherapy. The decrease in insulin sensitivity is hypothesized to be associated with defects in glucose and lipid metabolism and increased adiposity

Treatment effects of antipsychotic/valproate combination therapy on different components of insulin secretion and action, and treatment effects on abdominal versus peripheral adiposity, are unknown despite the availability of gold-standard methods and the prognostic significance of these issues. Relevant data are needed to target basic research, to identify the potential for acute and long-term complications, and to plan therapeutic interventions. The following specific aims will be addressed in non-diabetic schizophrenia patients treated with atypical antipsychotics who will be randomized to open label treatment with either valproate or no adjuvant. Evaluations are performed at baseline and 3 months of treatment.