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Are Nonsedating Antihistamines Really Nonsedating?

Although many patients find second-generation antihistamines to be less sedating, both first- and second-generation drugs can cause psychomotor impairment.

Second-generation antihistamines have become extremely popular because they are thought to be less sedating than their older counterparts. In this meta-analysis, researchers in Denver examined sedation and psychomotor impairment that resulted from either the first-generation antihistamine diphenhydramine or second-generation antihistamines (e.g., cetirizine, fexofenadine, loratadine). Eighteen randomized blinded studies were identified.

Both diphenhydramine and second-generation antihistamines caused significantly more psychomotor impairment and sedation than placebo did. Moreover, diphenhydramine caused significantly more psychomotor impairment and sedation than did the second-generation antihistamines. However, there were exceptions: In some individual studies, diphenhydramine did not cause more sedation or impairment than did placebo or second-generation drugs.

Comment: Although this meta-analysis supports the conclusion that second-generation antihistamines are less sedating than diphenhydramine on average, the authors note that outcomes were not consistent across all studies. The authors also suggest that the research was biased against diphenhydramine because most studies used 50-mg doses instead of the more commonly used 25-mg dose. In my own experience: (1) many, but certainly not all, patients find second-generation antihistamines to be less sedating; (2) some patients find diphenhydramine to be more sedating than other over-the-counter antihistamines, and (3) some patients prefer the expensive second-generation drugs as long as their cost is covered by insurance.

— Allan S. Brett, MD

Published in Journal Watch General Medicine May 6, 2003

Citation(s):

Bender BG et al. Sedation and performance impairment of diphenhydramine and second-generation antihistamines: A meta-analysis. J Allergy Clin Immunol 2003 Apr; 111:770-6.

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