Psychiatria pre prax 3/2026

Hyperprolactinemia as a potential cardiometabolic risk factor in antipsychotic treatment and the role of cariprazine

Schizophrenia is currently conceptualized as a multisystem disorder associated with significantly increased cardiovascular morbidity and mortality. This increased cardiometabolic risk is not solely attributable to antipsychotic treatment, but is already present prior to treatment initiation, driven by genetic factors and an unhealthy lifestyle. Antipsychotics may further potentiate this inherent risk through complex mechanisms involving modulation of receptor systems, hormonal regulation, and effects on peripheral organs. This review focuses primarily on hyperprolactinemia as a potential mediator of cardiometabolic risk. It discusses three major pathophysiological mechanisms underlying its potential effects: direct proatherogenic effects on blood vessels and the vascular endothelium; the development of hypogonadotropic hypogonadism, resulting in the loss of the cardioprotective effects of sex hormones; and the metabolic effects of prolactin in peripheral organs, including adipose tissue, the pancreas, and the liver. The review also examines subcellular mechanisms, including alterations in endothelial nitric oxide synthase (eNOS) and lipoprotein lipase activity, as well as prolactin-induced phenotypic switching of vascular smooth muscle cells. Large-scale clinical and epidemiological studies directly evaluating prolactin as a potential mediator of cardiovascular risk in patients with schizophrenia are currently lacking. Therefore, this review synthesizes available evidence from preclinical research and studies involving patients with prolactinomas. The final section summarizes current knowledge regarding the receptor profile of cariprazine. Its partial agonism at D2/D3 receptors is thought to underlie its minimal effects on prolactin levels, providing a potential rationale for reducing potential prolactin-mediated cardiometabolic risk, independently of the well-established cardiovascular risk factors associated with antipsychotic treatment. This review aims to provide a broader perspective on the role of prolactin in cardiovascular health and to contribute to the individualization of antipsychotic treatment.

Keywords: schizophrenia, hyperprolactinemia, cardiometabolic risk, antipsychotics, insulin resistance, cariprazine