Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: A literature review

First-generation antihistamines can have adverse effects on the central nervous system and thereby complicate discharge planning from the emergency department (ED). Newer antihistamines are potentially safer, causing less sedation with similar efficacy. The aim of this study was to review the literature to better define which antihistamines are good options for the treatment of acute allergic reactions. A Medline search was conducted to identify English language articles published between January 1975 and March 2006 on antihistamines, sedation, and acute allergic reactions. Bibliographies from included studies were further investigated. We focused on sedative potential, effect on cognitive function, efficacy, onset of clinical activity, and cost of antihistamines. Diphenhydramine impairs psychomotor performance and cognitive function. Loratadine and desloratadine are nonsedating but less efficacious than cetirizine or fexofenadine. The incidence of sedation with cetirizine is less than that of first-generation antihistamines but is greater than placebo. Cetirizine has the fastest onset of action among the newer antihistamines. Fexofenadine does not impair psychomotor or cognitive skills and shows no dose-related increase in sedation but has a slower onset of action than diphenhydramine and cetirizine. Newer antihistamines cost $0.52–2.39 more per dose than diphenhydramine ($0.37). Newer antihistamines provide similar efficacy as first-generation antihistamines but with less sedation. We believe this benefit outweighs the small increase in cost and that newer antihistamines should be considered in the management of acute allergic reactions. Although comparative ED-based trials are not available, newer antihistamines are an option for management of acute allergic reactions when sedation is a concern.