Vacchiano C, Moore J, Rice GM, Crawley G. Fexofenadine effects on cognitive performance in aviators at ground level and simulated altitude. Aviat Space Environ Med 2008; 79:754–60.Introduction: Antihistamines are used for the treatment of allergic rhinitis (AR) symptoms. However, the cognitive effects of some antihistamines can dramatically impair individuals in occupations that require sustained vigilance. Methods: The cognitive effects of fexofenadine were compared to a placebo (passive control) and cetirizine (active control) in healthy naval flight personnel. All subjects received one dose of each treatment in one of six possible sequences with two washout periods in between, and were assessed for aviation-related cognitive skills using the Aeromedical Vigilance Test (AVT) at both ambient atmospheric conditions and normobaric hypoxic conditions. Drowsiness was self-assessed by participants using a visual analog scale (VAS). Results: There was no significant difference between fexofenadine and placebo over the entire 60-min test period, under ambient atmospheric conditions, or under either hypoxic condition. Compared with placebo, cetirizine significantly increased AVT errors over the entire 60-min test period, at 10,000 ft, and at 15,000 ft. No statistical difference was found between treatments under ambient atmospheric conditions, although cetirizine treatment resulted in a greater change from baseline in adjusted average number of AVT errors (0.2124 ± 0.06) than fexofenadine treatment (0.1989 ± 0.07) and placebo (0.0745 ± 0.07). Furthermore, at 10,000 ft there were significantly more AVT errors with cetirizine than with fexofenadine. There were no significant increases in self-reported drowsiness (VAS) for both cetirizine and fexofenadine compared with placebo. Conclusion: Fexofenadine is comparable to placebo in its effect on the cognitive skills important for piloting an aircraft, while cetirizine impairs cognition and may affect piloting ability.