Antipsychotic drug-induced weight gain

Summary

Principal Investigator: TIMOTHY NAGY
Abstract: The new atypical antipsychotic drugs have proven to be very effective in the treatment of psychoses, however, one very alarming side effect of these drugs is excessive weight gain. In humans it has been shown that average weight gains of 4 to 4.5 kg can occur during a 10-week treatment period to nearly a 12 kg increase after one year of treatment. This increase in body weight is associated with an increase in impaired glucose tolerance and hypertension and therefore is likely to increase mortality rates. The mechanisms involved in the drug-induced weight gain are currently unknown. We have developed a mouse model in which we can induce weight gain with three of the currently available and commonly prescribed antipsychotic drugs (olanzapine, quetiapine, and risperidone). Weight gain in our model is reproducible and occurs within four weeks using twice-daily oral treatment. We hypothesize that olanzapine and quetiapine produce weight gain via increased food intake and risperidone produces weight gain by decreasing energy expenditure. We further hypothesize that these drug-induced changes in food intake and energy expenditure are due to differential changes in hypothalamic gene expression patterns relating to alternative mechanisms of regulating energy balance. Lastly, alterations either in food intake, body weight, and/or body composition, or the direct action of the drugs will produce decreases in insulin sensitivity in vivo. With the proposed studies, we will determine the mechanisms of drug-induced weight gain associated with these drugs. Once known, attempts could be made to avoid the deleterious side effects, or at least allow one to more accurately consider benefits versus risks dependent upon the presence of other confounding variables (family history of obesity, diabetes, and hypertension).
Funding Period: 2009-08-01 - 2010-06-30
more information: NIH RePORT

Top Publications

  1. pmc Effects of risperidone on energy balance in female C57BL/6J mice
    Xingsheng Li
    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
    Obesity (Silver Spring) 21:1850-7. 2013
  2. ncbi Antipsychotic drug-induced weight gain: development of an animal model
    M B Cope
    Department of Nutrition Sciences, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Int J Obes (Lond) 29:607-14. 2005
  3. ncbi No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs
    M B Cope
    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294 3360, USA
    Int J Obes (Lond) 31:1014-22. 2007
  4. pmc Risperidone alters food intake, core body temperature, and locomotor activity in mice
    Mark B Cope
    Department of Nutrition Sciences, University of Alabama at Birmingham, United States
    Physiol Behav 96:457-63. 2009

Detail Information

Publications4

  1. pmc Effects of risperidone on energy balance in female C57BL/6J mice
    Xingsheng Li
    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama
    Obesity (Silver Spring) 21:1850-7. 2013
    ..To investigate the effect of risperidone on energy expenditure and weight gain in female C57BL/6J mice...
  2. ncbi Antipsychotic drug-induced weight gain: development of an animal model
    M B Cope
    Department of Nutrition Sciences, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Int J Obes (Lond) 29:607-14. 2005
    ..Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition...
  3. ncbi No effect of dietary fat on short-term weight gain in mice treated with atypical antipsychotic drugs
    M B Cope
    Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294 3360, USA
    Int J Obes (Lond) 31:1014-22. 2007
    ..Atypical antipsychotic drugs (AAD) induce significant weight gain in female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids in this model is unknown...
  4. pmc Risperidone alters food intake, core body temperature, and locomotor activity in mice
    Mark B Cope
    Department of Nutrition Sciences, University of Alabama at Birmingham, United States
    Physiol Behav 96:457-63. 2009
    ....