Can we run away from the metabolic side effects of antipsychotics?

Antipsychotic (AP) medications are used to treat schizophrenia and a number off-label conditions. Although effective in reducing psychoses these drugs increase the risk of developing cardiometabolic disease, and are one of the reasons why individuals with schizophrenia live ∼15–20 years less than the general population. While weight gain has traditionally been thought to be the primary culprit linked to increases in rates of cardiometabolic disease, there are weight-gain independent effects of antipsychotics. The purpose of the current review was to highlight the acute metabolic complications of antipsychotics and to address the question: are exercise and targeting “exercise-activated” signaling pathways, a viable approach to offset the metabolic complications of APs? The possibility of fibroblast growth factor 21 being a common factor mediating the protective effects of exercise and certain nutritional approaches against the acute metabolic complications of antipsychotics was also discussed. The research highlighted in this narrative review provides evidence, in preclinical models, that exercise and certain exercise-activated pathways, can protect against acute perturbations in glucose metabolism. While promising, further work is needed to confirm these findings in clinical populations prescribed antipsychotics.