Antihistamines, drowsiness, and psychomotor impairment: central nervous system effect of cetirizine

Altered central nervous system function as indicated by drowsiness and impaired psychomotor performance is often a consequence of the use of traditional antihistamines. Demonstration that newer agents lack these CNS effects requires quantitive and objective measurements that are sensitive enough to assess the psychomotor capabilities required for such activities ad driving an automobile. These capabilities include extended attention span, vigilance, visual tracking, rapid information processing, and reaction time. We have used several psychomotor function tests to conduct two investigations assessing the CNS effects of cetirizine. In the first study, 12 healthy, atopic subjects received single oral doses of hydroxyzine 25 mg, cetirizine 10 mg and 20 mg, and placebo in a double-blind, four-way crossover study. Skin-wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 36 hours after each dose. The CNS effects were measured using critical flash-fusion frequency tests and Stroop word testing. Perceived feelings of drowsiness were measured using a visual analogue scale (VAS). In the second study, 15 healthy subjects received single oral doses of diphenhydramine 50 mg, cetirizine 5 mg, 10 mg, and 20 mg, and placebo in a double-blind, five-way crossover study. Skin-wheal response to intradermal histamine, psychomotor effects, and serum concentrations of each drug were measured for 24 hours after each dose. The CNS effects were measured using digit-symbol substitution testing, 'Trails-B' maze tracking, and an analyzer of driving performance that assessed reaction time and vigilance. These studies made possible a comprehensive assessment of cetirizine's pharmacokinetics and pharmacodynamics, relative to traditional antihisamines. Results from these trials suggest that cetirizine produces significant antihistaminic effects without significant CNS effects.