[Modern systemic therapy for pruritus].

Chronic pruritus (CP) is a highly prevalent, difficult to treat, and burdensome condition. Nowadays, multiple substances are available for the treatment of CP. Systemic therapies play a pivotal role in modern CP therapy, particularly in severe cases and those refractory to general antipruritic measures. Current guidelines recommend the use of a vast array of, mostly off-label, drugs with different mechanisms, including antihistamines, gabapentinoids, antidepressants, immunosuppressive drugs, and μ‑opioid receptor antagonists. The choice of the right agent depends on the indication, safety profile of the drug, and patient-specific features, such as comorbidities and comedication. Owing to a deeper understanding of the pathophysiology of CP, novel drugs have been developed and have already shown anti-pruritic efficacy in clinical studies and case reports. Of note, monoclonal antibodies, neurokinin‑1 receptor antagonists, Janus kinase inhibitors, and opioid receptor modulators are on the frontline of innovative CP treatment. Other promising targets include structures of the peripheral and central nervous system, e.g., histamine 4 receptors, which are involved in itch signaling. This review provides an overview of currently available systemic therapies for CP and their indications and discusses novel innovative agents and promising new targets in CP.