Sleepiness and performance during three-day administration of cetirizine or diphenhydramine

The sedative effects of cetirizine (10 mg once daily), diphenhydramine (50 mg three times daily), and placebo, each administered during a 3-day period, were compared with objective measures of sleepiness and performance.

Twelve atopic subjects received each of the three treatments for 3 consecutive days in a double-blind Latin square design. Subjects received either cetirizine at 8:00 AM and placebo at 3:00 PM and 10:00 PM; diphenhydramine at 8:00 AM, 3:00 PM, and 10:00 PM; or placebo at all three times. Sleepiness was measured on days 1 and 3 with the multiple sleep latency test at 9:00 AM, 11:00 AM, 1:00 PM, 3:00 PM, and 5:00 PM. Performance was assessed with a 60-minute simulated assembly line task at 9:30 AM, 11:30 AM, 1:30 PM, and 3:30 PM. Nightly sleep duration was estimated with actigraphy.

Compared with placebo and cetirizine, diphenhydramine produced marked impairment only on the first day of drug administration. The multiple sleep latency test and the simulated assembly line task values remained stable across days with cetirizine and placebo but improved with diphenhydramine, resulting in no differences among the three conditions on the third day.

Unlike cetirizine, diphenhydramine produced acute impairment of alertness and performance. By the third day of administration, however, this impairment was no longer present, apparently because of development of tolerance to the sedative effects.