The effects of antihistamines on cognition and performance

Allergic diseases are responsible for substantially more disability than is generally realized. Allergic rhinitis alone results in 3.5 million lost wo rkdays and 2 million missed school days in the United States each year. Com orbid conditions such as asthma and sinusitis can be disabling as well, res ulting each year in more than 10 million missed school days and more than 7 3 million days of restricted activity, respectively. Antihistamines continu e to be the mainstay of treatment for allergic disorders. In the case of th e first-generation antihistamines, however, the treatment may well be worse than the disease. Although these agents are effective H-1-receptor antagon ists, they are also highly lipophilic and readily cross the blood-brain bar rier, causing considerable sedation. The second-generation agents are more lipophobic and possess different ionic charges than the first-generation an tihistamines, As a result, they are far less likely to cross the blood-brai n barrier and, for that reason, cause little if any sedation. In a recent c omparative trial, subjects who were treated with the first-generation agent diphenhydramine were found to have significant performance deficits on tes ts of divided attention, working memory, vigilance, and speed. By contrast, subjects who were treated with the second-generation antihistamine loratad ine performed as well as subjects who were treated with placebo. The sedati ve effects of the first-generation agents persist well into the next day an d thus can potentially interfere with daytime performance and safety even w hen taken the night before. It is therefore recommended that patients whose occupations require vigilance, divided attention, or concentration receive only second-generation antihistamines.