ABSTRACT
Objectives: To evaluate the acute effects of two histamine H1-receptor antagonists on nocturnal sleep architecture and on next day cognitive function and psychomotor performance.
Methods: This was a single-site, randomized, double-blind, 3-way crossover study, comparing the effects of a single dose of chlorpheniramine (6 mg), fexofenadine (120 mg) and placebo in 18 healthy (male and female) Japanese volunteers aged 20–55 years. Volunteers were resident for 3 days and each period was separated by a minimum 5‐day washout period. The three treatments were administered at 23.00 h. Overnight sleep was measured from 23.00 h to 07.00 h using polysomnography. Residual effects were studied at 07.00 h and 9.00 h the next morning, with the latency to sleep (sleep latency test) measured at 09.30 h.
Results: Compared with placebo, chlorpheniramine increased the latencies to sleep onset and rapid eye movement (REM) sleep ( p ≤ 0.05 for both), and reduced the duration of REM sleep ( p ≤ 0.01), but this was not observed with fexofenadine. As far as residual effects the next morning were concerned there were decrements in performance with chlorpheniramine, but not with fexofenadine. Chlorpheniramine 6 mg impaired divided attention ( p < 0.001), vigilance ( p < 0.05), working memory ( p < 0.0001) and sensori-motor performance ( p < 0.01), and the latency to daytime sleep was reduced ( p < 0.0001). Six adverse events possibly related to study medication were reported during the study, three of which were related to placebo, two to fexofenadine and one to chlorpheniramine.
Conclusion: These findings suggest that a single nocturnal dose of fexofenadine has advantages over the first-generation antihistamine chlorpheniramine, being free of disruption of night-time sleep and detrimental effects on cognitive performance the next day. It is likely that this advantage will remain with chronic ingestion, but this would need to be confirmed.