CHARACTERIZATION OF DAYTIME SLEEPINESS AND PSYCHOMOTOR PERFORMANCE FOLLOWING H-1 RECEPTOR ANTAGONISTS

Background: While first generation H-2-receptor antagonists are widely used, there are relatively few data describing their comparative effe cts on subjective daytime sleepiness and psychomotor performance. Obje ctive: To compare the effects of first generation H-1 receptor antagon ists on subjective daytime sleepiness and psychomotor performance. Met hods: We conducted two single-dose, cross-over studies. In the first, we validated our methodology in 18 healthy subjects by examining the r esponse to diphenhydramine (50 mg), terfenadine (60 mg), and placebo. In the second trial, we evaluated the relative effects following diphe nhydramine (50 mg), diphenhydramine (25 mg), chlorpheniramine (4 mg), and placebo. Psychomotor tests included choice reaction time, hand ste adiness, and a test that divided attention between tracking and reacti on time. Introspective drowsiness was measured using a visual analog s cale 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. Results: In the firs t trial, 50 mg diphenhydramine produced significant impairment relativ e to placebo in both subjective and objective assessments (P <.05). Re sponses following terfenadine did not differ from placebo. In the seco nd study, all three regimens produced subjective and objective soporif ic 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 not ed one and three hours after dosing (P <.05). The general rank order o f effects was diphenhydramine (50 mg), followed by diphenhydramine (25 mg), followed by chlorpheniramine (4 mg). Significant differences amo ng the three regimens were, for the most part, confined to greater sop orific effects from diphenhydramine relative to chlorpheniramine (P <. 05). Conclusions: Taken together, our observations confirm that subjec tive 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 r egimens of first-generation compounds.