Pharmacogenetics of antipsychotic-induced weight gain

Abstract

Weight gain appears to be a serious side effect encountered during treatment with many antipsychotic drugs. Although the propensities of inducing weight gain vary considerably between antipsychotics, weight gain is mostly observed in atypical antipsychotics, increasingly prescribed for a variety of psychiatric disorders. Beside the psychological consequences weight gain may influence patients' compliance and secondary medical comorbidities related to being overweight may arise, including diabetes, hypertonia, respiratory problems, and some types of cancer. Obesity research generally suggests that a complex system of neurotransmitters, neuropeptides, hormones and immune related factors interact in neural circuits involving at least the hypothalamus, the solitary tract and cortical structures to regulate energy homeostasis and body weight. Antipsychotics that have weight gain inducing properties may disrupt associated pathways at any of these levels, although it remains unclear what the mechanisms of action might be. Given the potential deleterious effects of weight gain, individual predictors of weight gain would be extremely helpful at the beginning of pharmacological treatment with atypical antipsychotics, allowing obesity to be avoided or for counteractive steps such as dietary restrictions to be taken in predisposed individuals. So far, only a few predictors to detect individuals at high risk have been reported and these have limited power. It is likely that genetic factors play a major role in determining individual response to antipsychotics as well as their side effect profile. In this article, we have reviewed literature related to antipsychotic-induced weight gain and have discussed the major issues, before updating the reader on current obesity research findings. Finally, we emphasize previous studies relating to the pharmacogenetics of antipsychotic-induced weight gain.