Effect of Antipsychotics on Appetite Regulation

Severe weight gain and glucose dysregulation are serious problems in patients treated with second-generation ('atypical') antipsychotics (SGA). These side effects frequently interfere with medication compliance and necessitate discontinuation of treatment. Although the causal mechanisms for weight and glucose dysregulation are not well understood, one promising area of investigation targets SGA-induced disturbances in appetite and in appetite-regulating hormones. Findings from our group (and others) demonstrate SGA treatment-related increases in fasting levels of the appetite-stimulating hormone, ghrelin, as well as increases in self-report hunger. This novel study will examine prospective changes in ghrelin and in the 'satiety-signaling' peptide YY (PYY) as measured before and after participants consume a standard mixed-macronutrient meal. Data are obtained at baseline (within 4 weeks of beginning medication), and again 2 months and 4 months later.

Inclusion criteria

• Meets DSM IV criteria for a psychotic disorder (schizophrenia, schizophreniform, brief psychotic disorder, schizoaffective disorder), bipolar disorder, or major depression with psychotic features;
• "Drug naïve" prior to most recent psychiatric diagnosis;
• Currently prescribed one of four atypical antipsychotic medications: olanzapine, risperidone, ziprasidone, or aripiprazole;
• Between the ages of 18 and 40, any race and either gender;
• Not obese (BMI < 30 kg/m2) (fasting and postprandial ghrelin levels are altered in obesity);
• Has negative histories for cardiovascular, metabolic, and endocrine disorders at screening;
• Is willing and able to eat animal-derived foods; and
• Is not exercising 3 or more times per week.

Exclusion criteria

• Use of medications to treat metabolic and endocrine abnormalities, corticosteroids, over-the-counter appetite suppressants that contain phentermine or Sibutramine;
• Active involvement with a weight loss program (i.e., Weight Watchers);
• Serious or unstable medical illness which requires ongoing treatment with medication (this does not include hypertension);
• Anemia;
• At serious suicidal risk;
• Current substance abuse or dependence;
• For female subjects, pregnancy or nursing (because pregnancy may influence appetite and because the body composition procedure involves low level X-ray exposure).
• Known history of mental retardation or dementia.
• Children and adolescents under age 18 will be excluded owing to the inherent confounding effects of normal growth on body weight and appetite.