Side Effects of Antipsychotic Medications

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00363181
Recruitment Status : Unknown
Verified March 2007 by Stanford University.
Recruitment status was:  Recruiting
First Posted : August 15, 2006
Last Update Posted : March 21, 2007
Information provided by:
Stanford University

Brief 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.

Condition or disease
Insulin Resistance Metabolic Syndrome X Schizophrenia and Disorders With Psychotic Features Mood Disorders Psychotic Disorders

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.

Study Type : Observational
Enrollment : 120 participants
Observational Model: Defined Population
Observational Model: Natural History
Time Perspective: Cross-Sectional
Time Perspective: Prospective
Official Title: Does Olanzapine Inhibit the Secretory Response to Insulin Resistance?
Study Start Date : April 2006

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Ages Eligible for Study:   30 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants 30-66 years of age
  • Body mass index (BMI) >25 < 35 kg/m2.
  • Fasting plasma glucose concentration < 126 mg/dL
  • Stable on one of the following psychiatric medication: Olanzapine (Zyprexa®), Ziprasidone (Geodon®), Aripiprazole (Abilify®), or Risperidone (Risperdal®)
  • Stable on psychiatric medication for at least 3 months

Exclusion Criteria:

  • Medications that directly affect insulin-mediated glucose disposal
  • Intense suicidal impulses/intent
  • Alcohol or substance abuse for 3 months.
  • Major medical problems, i.e., clinically unstable medical disorder or condition; cardiovascular, hepatic, renal, gastrointestinal, pulmonary, endocrine or other systemic disease that would, in the investigator's clinical judgment interfere with the endocrine measures obtained in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00363181

Contact: Lilla Nikolics, Ms 650-493-5000 ext 67289
Contact: Contact email

United States, California
VA Palo Alto Health Care System Recruiting
Palo Alto, California, United States, 94304-1290
Principal Investigator: Steven E Lindley, MD, PhD         
Sponsors and Collaborators
Stanford University
Principal Investigator: Steven E Lindley, MD, PhD Stanford School of Medicine / VA Palo Alto
Principal Investigator: Gerald M Reaven, MD Stanford School of Medicine Identifier: NCT00363181     History of Changes
Other Study ID Numbers: F1DMC-X280
First Posted: August 15, 2006    Key Record Dates
Last Update Posted: March 21, 2007
Last Verified: March 2007

Keywords provided by Stanford University:
Insulin resistance
Metabolic problems
Weight gain
Mental health problems
Mental disorders
Antipsychotic medication

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Mental Disorders
Psychotic Disorders
Mood Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents