Effect of Weight - Increasing Psychotropic Medications on Appetite Regulation

Project: Research project


Patients treated with second-generation (Â?atypicalÂ?) antipsychotic and mood stabilizers frequently experience severe weight gain that leads to obesity and obesity-related disorders, interferes with medication compliance, and necessitates discontinuation of treatment. Along with the weight gain, patients often report significant increases in appetite and persistent insatiability. The biological mechanisms underlying weight gain and increased appetite in patients treated with psychotropic medications are unknown.
Short-term (3 months) treatment with the atypical antipsychotic, olanzapine, increases respiratory quotient and central body fat %, suggesting an energy utilization/storage pathway leading to weight gain. Olanzapine also increases fasting levels of the appetite-stimulating hormone, ghrelin, suggesting another pathway hinged on appetite and energy over-consumption. In non-patient samples, fasting ghrelin is lower in obese vs. non-obese individuals. Therefore, the concomitant increase in ghrelin and body weight in patients secondary to antipsychotic treatment seems counterintuitive and warrants further investigation.
We have shown that obese individuals who experience less postprandial ghrelin suppression report increased postprandial Â?urge to eatÂ? and sweet cravings after high carbohydrate but not high fat meals. In addition, obese individuals have a deficiency in the appetite-suppressing neuropeptide YY (PYY). No studies have examined the effects of psychotropic medication use on PYY, nor postprandial ghrelin or PYY responses in patients treated with weight-increasing medications. Critical gaps include studies that assess changes in appetitive hormones over a typical course of antipsychotic treatment, that include fasting and postprandial hormone measurements, and that relate changes in biological and psychological appetitive constructs with weight and weight-related outcomes.
The proposed study will evaluate prospectively changes in ghrelin and PYY, perceived hunger, and resting metabolism in drug-naïve patients treated with atypical antipsychotics that have high weight-gain liability. Outcomes will be compared to those measured in patients treated with an antipsychotic with low weight gain liability, patients who refuse antipsychotic treatment, patients treated with a high weight gain liability mood stabilizing agent, and healthy unmedicated controls. We will also examine the relation of treatment-induced changes in appetitive hormones with changes in body composition, metabolism, and postprandial appetite.
Findings will address critical mechanistic questions regarding appetite dysregulation as it pertains to the pervasive clinical challenge of psychotropic medication-induced weight gain, obesity, and diabetes. Ultimately, information gained from this study may be instrumental in reducing obesity and obesity-related morbidities in patients with severe mental illness.
Effective start/end date9/15/078/31/12


  • NIH National Institute of Mental Health (NIMH)


Appetite Regulation
Weight Gain
Weights and Measures
Antipsychotic Agents
Medication Adherence
Body Composition
Adipose Tissue
Body Weight