Glucose and Lipid Metabolism on Antipsychotic Medication
Condition: Schizophrenia; Schizoaffective Disorder; Type 2 Diabetes Mellitus; Hyperglycemia
MeSH terms: Diabetes Mellitus, Type 2; Hyperglycemia; Schizophrenia; Psychotic Disorders
Study type: Interventional

Summary: 
      This project aims to a) evaluate the effects of selected antipsychotic medications on insulin
      action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue
      (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on
      abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the
      longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid
      profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These
      hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the
      use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual
      energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in
      glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic
      schizophrenia patients chronically treated with risperidone, olanzapine, clozapine,
      quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will
      also be performed in patients who are randomized to switch from their current antipsychotic
      (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months.
      Relevant data is critically needed to target basic research, identify long-term
      cardiovascular consequences, and plan therapeutic interventions.
    

Detailed description: 
      Hyperglycemia and type 2 diabetes mellitus are more common in schizophrenia than in the
      general population. Type 2 diabetes mellitus is characterized by disturbances in insulin
      action on skeletal muscle, liver and adipose tissue. Diabetes causes increased morbidity and
      mortality due to acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular
      disease) complications. The combination of hyperglycemia, dyslipidemia and abdominal
      adiposity is even more strongly associated with increased cardiovascular morbidity and
      mortality. The association of type 2 diabetes and hyperglycemia with schizophrenia was first
      noted prior to the introduction of antipsychotic medications, suggesting that these patients
      may be at increased risk. Since then, however, additional glucoregulatory abnormalities
      (e.g., new onset diabetes), dyslipidemia, and increased weight and adiposity have all been
      associated with antipsychotic medications. Concern about antipsychotic effects on glucose,
      lipids and adiposity has increased recently, focusing on the widely-used newer medications,
      clozapine and olanzapine. Increased abdominal adiposity can secondarily decrease insulin
      sensitivity and antipsychotics can increase adiposity. However, medication effects on glucose
      control and insulin action may also occur independent of differences in adiposity. This
      project aims to a) evaluate the effects of selected antipsychotic medications on insulin
      action in skeletal muscle (glucose disposal), liver (glucose production) and adipose tissue
      (whole-body lipolysis), b) evaluate the effects of selected antipsychotic medications on
      abdominal adipose tissue mass, total body fat and total fat-free mass, and c) explore the
      longitudinal effects of treatment with selected antipsychotics on glucose tolerance, lipid
      profiles, abdominal adipose tissue mass, total body fat and total fat-free mass. These
      hypotheses will be evaluated by measuring 1) whole-body glucose and lipid kinetics with the
      use of "gold-standard" stable isotope tracer methodology, 2) body composition using dual
      energy x-ray absorptiometry and magnetic resonance imaging, and 3) longitudinal changes in
      glucose tolerance and lipid profiles. The aims will be addressed in non-diabetic
      schizophrenia patients chronically treated with risperidone, olanzapine, clozapine,
      quetiapine, ziprasidone, or haloperidol, and untreated healthy controls. Re-evaluations will
      also be performed in patients who are randomized to switch from their current antipsychotic
      (from the above groups) to risperidone, olanzapine, quetiapine, or ziprasidone for 6 months.
      Relevant data is critically needed to target basic research, identify long-term
      cardiovascular consequences, and plan therapeutic interventions.
    

Intervention name(s): risperidone; olanzapine; quetiapine; ziprasidone
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): randomized to 12 week trial of risperidone.; randomized to 12 week trial of olanzapine.; randomized to 12 week trial of quetiapine.; randomized to 12 week trial of ziprasidone.
Other intervention name(s): Risperdal; Zyprexa; Seroquel; Geodon
Intervention MeSH terms: Olanzapine; Risperidone; Quetiapine Fumarate; Ziprasidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: control; risperidone; olanzapine; quetiapine; ziprasidone