The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel.

Background: Sedation and functional impairments are side effects associated with the use of first-generation antihistamines that preclude their use in aviation. Selected second-generation antihistamines do not have such side effects and have been proposed for use in aircrew. Methods: Forty-two healthy naval aviation personnel served as subjects in this double-blind, randomized, placebo-controlled crossover study. Subjective drowsiness, cognitive performance, and vigilance were measured under three conditions: 180 mg fexofenadine (F), 50 mg diphenhydramine (D) as a positive control, or placebo (P). Results: Subjects receiving F vs. D tended to have a faster mean hit reaction time (adjusted mean difference ± SE, -10.5 ± 6.8 ms, p = 0.127). Subjects performed faster and better with F vs. D on measures of omission errors and commission errors (p < 0.05). Variable symbol digit coding delayed recall accuracy was better for F vs. D (p = 0.023), and approached significance for shifting attention and divided attention tasks (p = 0.062 and p = 0.057, respectively). Subjects reported significantly more drowsiness (p < 0.005) with D than F. Conclusions: Diphenhydramine administration resulted in significant psychomotor decrements compared with fexofenadine, while the effects of fexofenadine were similar to placebo. These results provide additional support for the safe use of fexofenadine by aviation personnel.