Preclinical models of antipsychotic drug-induced metabolic side effects

Antipsychotic drugs (APDs), and the ‘atypical’ APDs in particular, are commonly associated with metabolic side effects in humans. These include glucose dysregulation, insulin resistance, hyperlipidemia, weight gain and hypertension, which put patients at increased risk of cardiometabolic disorders. The underlying biology of APD-induced side effects in humans is poorly understood, and therefore preclinical rodent models are essential for translational research. With numerous recent studies on the topic, there is an emerging consensus that some symptoms, such as glucose dysregulation and insulin resistance, are more reliably observed than others, such as weight gain and hypertension, but, comparison between preclinical studies is complicated by numerous factors, including drug-specific effects and variables such as diet and treatment regimen. In this paper, we provide a major review of this important and growing field of preclinical study, and address crucial issues for future research.