Metabolic effects of atypical antipsychotics: Molecular targets

Atypical antipsychotics (AAPs) are commonly prescribed drugs in the treatment of schizophrenia, bipolar disorder and other mental diseases with psychotic traits. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with undesired metabolic side effects, including metabolic syndrome (MetS). MeS is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which predispose to type 2 diabetes (T2D) and cardiovascular disease. In this review, the molecular and cellular mechanisms involved in these undesired metabolic abnormalities induced by AAPs are described. These mechanisms are complex as AAPs have multiple cellular targets which significantly affect the activities of several hormones and neuromodulators. Additionally, AAPs affect all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better understanding of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinically different side effects of distinct AAPs is needed. This knowledge will help in the development of novel AAPs with less adverse effects as well as of adjuvant therapies to patients receiving AAPs.