Preclinical and Clinical Sex Differences in Antipsychotic-Induced Metabolic Disturbances: A Narrative Review of Adiposity and Glucose Metabolism

Antipsychotic (AP) medications are associated with an increased risk of developing metabolic side effects including weight gain, type 2 diabetes (T2D), dyslipidemia, and hypertension. In the majority of clinical studies, females on APs are noted to gain more weight, and are more likely to be diagnosed with metabolic syndrome when compared to males. However, the data is less clear when comparing sex disparities associated with other specific AP-induced metabolic risk factors. Accumulating evidence has demonstrated a role for AP-induced adipose tissue accumulation as well as whole body glucose dysregulation in male models that is independent of changes in body weight. The purpose of this narrative review is to explore the susceptibility of males and females to changes in adiposity and glucose metabolism across clinical and preclinical models of AP treatment. It is important that future research examining AP-induced metabolic side effects analyzes outcomes by sex to help clarify risk and identify the mechanisms of adverse event development to improve safe prescribing of medications.