Serotonergic effects of chlorpheniramine: An unexplored advantage of the first-generation antihistamine

Chronic and refractory pruritus remains a therapeutic challenge, often unresponsive to traditional antihistamines and associated with significant psychiatric comorbidity. Conditions such as refractory urticaria and senile pruritus frequently coexist with anxiety, depression, and sleep disturbances, complicating management. While chlorpheniramine is a well-established first-generation antihistamine, its lesser-known serotonergic activity presents a unique opportunity for repurposing. This article explores the serotonergic profile of chlorpheniramine and its potential to alleviate both somatic and psychological components of pruritus. By synthesizing evidence from dermatology, neuropharmacology, and psychodermatology, we assess how chlorpheniramine represents a low-cost, centrally acting agent capable of addressing the multidimensional burden of chronic pruritus.