Diphenhydramine: It is time to say a final goodbye

Diphenhydramine, once a pioneering antihistamine, is now overshadowed by second-generation antihistamines with similar efficacy and fewer adverse effects. Current data suggest that the adverse side-effect profile of diphenhydramine is higher among children and older adults. This has led to countries such as Germany and Sweden restricting access to first-generation antihistamines and societal guidelines advocating for the use of second-generation antihistamines. Despite its well-documented problematic therapeutic ratio, diphenhydramine remains available in over 300 formulations, most of which are over-the-counter. Based on a comprehensive evaluation of practice patterns and the prevalence and incidence of adverse clinical events, we believe that diphenhydramine has reached the end of its life cycle, and in its class of therapies it is a relatively greater public health hazard. We recommend it should no longer be widely prescribed or continue to be readily available over the counter.