Characterization of daytime sleepiness and psychomotor performance following H1 receptor antagonists

While first generation H1-receptor antagonists are widely used, there are relatively few data describing their comparative effects on subjective daytime sleepiness and psychomotor performance.

To compare the effects of first generation H1 receptor antagonists on subjective daytime sleepiness and psychomotor performance.

We conducted two single-dose, cross-over studies. In the first, we validated our methodology in 18 healthy subjects by examining the response to diphenhydramine (50 mg), terfenadine (60 mg), and placebo. In the second trial, we evaluated the relative effects following diphenhydramine (50 mg), diphenhydramine (25 mg), chlorpheniramine (4 mg), and placebo. Psychomotor tests included choice reaction time, hand steadiness, and a test that divided attention between tracking and reaction time. Introspective drowsiness was measured using a visual analog scale and the Stanford Sleepiness Scale. Assessments were made prior to dosing and at one, three, and five hours after dosing; a 7-hour post-drug assessment was included in the second trial.

In the first trial, 50 mg diphenhydramine produced significant impairment relative to placebo in both subjective and objective assessments (P < .05). Responses following terfenadine did not differ from placebo. In the second study, all three regimens produced subjective and objective soporific effects to a significantly greater degree than placebo. For example, significant introspective sleepiness was noted three hours following all three regimens (P < .05) and slower choice reaction times were noted one and three hours after dosing (P < .05). The general rank order of effects was diphenhydramine (50 mg), followed by diphenhydramine (25 mg), followed by chlorpheniramine (4 mg). Significant differences among the three regimens were, for the most part, confined to greater soporific effects from diphenhydramine relative to chlorpheniramine (P < .05).

Taken together, our observations confirm that subjective and objective measures of sleepiness and psychomotor performance occur following single doses of diphenhydramine and chlorpheniramine, but not terfenadine. Differences in soporific effects do exist among regimens of first-generation compounds.