• fsIVGTTs, lipid profiles and measurement of plasma hsCRP, ghrelin, adiponectin and leptin levels are done at baseline and 6 weeks on antipsychotic monotherapy, valproate is added, and a final evaluation is performed at 18 weeks.
  

• Body composition using dual energy x-ray absorptiometry, magnetic resonance scans and anthropomorphic measurements are done at baseline, 6 week and 18 week visits.
  

Hyperglycemia and type 2 diabetes mellitus may be more common in schizophrenia than in the general population. Hyperglycemia was first noted in patients with schizophrenia prior to the introduction of antipsychotic medications, but glucoregulatory defects, dyslipidemia and increased adiposity are all associated with both older and newer antipsychotic treatments. Schizophrenia is associated with increased rates of obesity, hyperglycemia, dyslipidemia and type 2 diabetes mellitus, causing increased morbidity and mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., vascular disease) complications.

Currently, olanzapine and risperidone are the most commonly prescribed antipsychotics, as well as being the first and second, respectively, most costly drugs for Medicaid in Missouri and many other states. In addition to antipsychotic medications, schizophrenia patients are commonly exposed to multi-class polypharmacy with medications other than antipsychotics. Valproate, another costly (i.e., top 10) medication for Medicaid, is frequently used in the adjunctive treatment of schizophrenia, recently co-prescribed to as many as 35% of schizophrenia patients. While polypharmacy often aims to improve treatment efficacy and effectiveness, little quantitative data is available concerning the metabolic consequences of such medication combinations.

This project aims to study the effect of antipsychotic treatment with and without valproate on glucose and lipid metabolism and weight regulation.

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 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 haloperidol, olanzapine or risperidone who will be receive open label treatment with valproate. Evaluations are performed at baseline and 6 weeks on antipsychotic monotherapy, valproate is added, and a final evaluation is performed at 18 weeks.