Side Effects of Antipsychotic Medications
Condition: Insulin Resistance; Metabolic Syndrome X; Schizophrenia and Disorders With Psychotic Features; Mood Disorders; Psychotic Disorders
MeSH terms: Metabolic Syndrome; Insulin Resistance; Schizophrenia; Mental Disorders; Psychotic Disorders; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders
Study type: Observational

Summary: 
      Medications like olanzapine have been associated with the development of weight gain and
      diabetes in some patients. It is not known if the increased risk of developing diabetes is a
      direct effect on insulin or simply related to weight gain.

      We hope to learn in this study whether or not olanzapine directly slows down insulin
      secretion from the pancreas, thereby increasing the risk of developing diabetes.
    

Detailed description: 
      Objectives: The use of atypical antipsychotics has been associated with increased weight
      gain, the development of type-2 diabetes, and, in rare cases, diabetic ketoacidosis. It is
      not clear if these changes are a direct function of antipsychotics on either insulin action
      or insulin secretion, or simply related to their ability to induce weight gain in a
      population at increased risk to develop hyperglycemia. The objective of this investigation is
      to determine if treatment with the atypical antipsychotics olanzapine impairs the ability of
      the pancreatic beta cell to increase its insulin secretory response to graded increases in
      plasma glucose concentration in non-diabetic, insulin resistant individuals. In addition, we
      will compare the range of insulin-mediated glucose uptake (IMGU) in olanzapine-treated versus
      non-antipsychotic treated patients.

      Research Plan and Methods: 120 subjects with psychiatric disorders will be enrolled; 60
      patients on olanzapine and 60 patients with similar psychiatric diagnoses on a different
      antipsychotic medication (ziprasidone, risperidone or aripiprazole). All subjects will have a
      fasting plasma glucose concentration <126 mg/dL, and on no medication with a direct effect on
      IMGU. Subjects will be admitted to the General Clinical Research Center (GCRC) at Stanford
      Medical Center and evaluated by an insulin suppression test (IST) to determine their IMGU.
      Subjects with a steady state plasma glucose (SSPG) concentration during the IST that is >180
      mg/dL will be defined as being insulin resistant. From this population of subjects, 15
      patients on olanzapine and 15 patients not on any antipsychotic, will return to the GCRC to
      determine their glucose-stimulated insulin secretory dose-response curves (GS-ISR). The
      GS-ISR at the same glucose concentration will be compared between the subjects on olanzapine
      (n=15) and the not on an antipsychotic (n=15) by analysis of variance. Analyses of the 120
      subjects screened for insulin resistance will compare 1) the means and distribution of the
      SSPG concentrations in olanzapine and non-olanzapine treated patients with psychiatric
      diagnoses; and 2) the means of the two experimental groups with psychiatric diagnoses to Dr.
      Reaven's data base of volunteers without psychiatric disorders.
    

Time perspective: Prospective
Keywords: Insulin resistance; Metabolic problems; Weight gain; Mental health problems; Mental disorders; Antipsychotic medication; Olanzapine