This article evaluates and summarizes the results of studies investigating the central nervous system effects of second-generation antihistamines, with particular emphasis on psychomotor and cognitive effects. The data sources were computer-assisted MEDLINE searches using the search terms histamine H1antagonists, psychomotor performance, sleep, and specific drug names, including astemizole, cetirizine, loratadine, and terfenadine; the searches were limited to studies in humans. Only controlled studies (placebo or active control or both) using standardized or quantitative methods for defining drug-induced effects on sedation, psychomotor performance, or cognition were reviewed. Additional published studies were identified within the references of the first group of studies. Finally, representative studies were selected for summarization. Objective and subjective measures of sedation show that loratadine and terfenadine produce sedation at a rate comparable with placebo. Moreover, these agents, when used at standard therapeutic doses, do not produce detrimental effects on objective measures of psychomotor or cognitive function. Cetirizine is associated with sedation or psychomotor impairment in some studies but not in others. The data on central nervous system effects of astemizole are limited and were not evaluated. The absence of sedation and psychomotor or cognitive impairment in patients receiving loratadine or terfenadine justifies the cost of these agents, particularly for patients who drive, pilot aircraft, or operate machinery. Whether the potential for rare but serious cardiovascular events (associated with astemizole and terfenadine) is justifiable must be decided on a case-by-case basis.
Arch Intern Med. 1997;157:494-500
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