Antipsychotic-Induced Dysregulation of Glucose Metabolism Through the Central Nervous System: A Scoping Review of Animal Models

The use of antipsychotic drugs is associated with adverse metabolic effects. Disruptions in glucose metabolism such as hyperglycemia and insulin resistance have been shown to occur with antipsychotic use, independent of changes in body weight or adiposity. The regulation of whole-body glucose metabolism is partly mediated by the central nervous system. In particular, the hypothalamus and brainstem are responsive to peripheral energy signals and subsequently mediate feedback mechanisms to maintain peripheral glucose homeostasis. In this scoping review of preclinical in vivo studies, we aimed to explore central mechanisms through which antipsychotics dysregulate glucose metabolism. A systematic search for animal studies identified 29 studies that met our eligibility criteria for qualitative synthesis. The studies suggest that antipsychotic-induced changes in autonomic nervous system activity, certain neurotransmitter systems, expression of neuropeptides, and central insulin action mediate impairments in glucose metabolism. These findings provide insight into potential targets for the mitigation of the adverse effects of antipsychotics on glucose metabolism.