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Editor's Correspondence
September 28, 1998

First-Generation vs Second-Generation Antihistamines

Arch Intern Med. 1998;158(17):1949-1950. doi:

In reply

I appreciate the interest of Aelony in our study. His comments, however, suggest that he missed an important point of our article. Our study focused on determining the initial and steady-state effects of loratadine, a second-generation antihistamine, not demonstrating the well-established fact that diphenhydramine is a sedating drug. Prior to our study, there was only 1 other that reported on an investigation of the steady-state effects of loratadine on cognition, and that article is written in German.1 Diphenhydramine was included in our study as a positive-control substance. A positive control is used in pharmacological studies to demonstrate the sensitivity of the tests being used to measure the effect under investigation. If we had failed to demonstrate sedation with diphenhydramine, the sensitivity of our test battery would be called into question. The information that is considered useful to clinicians is not the fact that diphenhydramine is a sedating drug. Diphenhydramine is the most popular over-the-counter sleep aid! Rather, the information considered useful to clinicians was the finding that initial and steady-state doses of loratadine were no more sedating than placebo, and that its effects on measures of cognition, psychomotor performance, mood, and self-reported sleepiness were not different from those with placebo.