To evaluate the acute effects of two histamine H(1)-receptor antagonists on nocturnal sleep architecture and on next day cognitive function and psychomotor performance.
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.
Compared with placebo, chlorpheniramine increased the latencies to sleep onset and rapid eye movement (REM) sleep (p < or = 0.05 for both), and reduced the duration of REM sleep (p <or= 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.
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.
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"Allergic rhinitis, for instance, is associated with sleep loss or an impaired sleep pattern  through nasal obstruction and the enlargement of tonsils and adenoids. On the other hand, allergy medication may impair sleep architecture for instance by increasing the latencies to sleep onset and reducing the REM sleep duration . However, due to the cross-sectional nature of this study, we do not know the cause-effect direction of the association and it is not possible to rule out that lack of sufficient sleep is a risk factor for allergy onset instead of the more intuitive relationship between allergy nasal obstructive symptoms and sleep disturbances. "
[Show abstract][Hide abstract] ABSTRACT: Some health behaviours are liable to affect the incidence of allergies and/or common infections in young people; however, the extent and ways in which these might occur are mostly unknown. This study examines the association of health behaviours related to physical activity, sedentariness, diet and sleep with allergy and infection symptoms in adolescents, and also with biological markers that might mediate disease incidence.
The study comprised a total of 2054 adolescents (50.7% girls) from the Madrid region of Spain. The incidence of infection and allergy symptoms three months prior to the study was obtained from a self-administered questionnaire. Physical and sedentary activities, height and weight, food habits and sleep duration were also self-reported and their influence on infection and allergy incidence was assessed by logistic regression analysis. Blood biomarkers (IgE, eosinophil percentage, leptin, interleukin (IL)-2, IL-4, IL-5 and IL-10) were evaluated in a subsample of 198 subjects.
Adequate sleep duration (OR = 0.79, 95%CI: 0.64 to 0.97) and unhealthy weight status (overweight/obesity) (OR = 1.35, 95%CI: 1.04-1.74) were independently associated with decreased and increased allergy incidence, respectively. No significant association was observed with infection incidence. IgE and leptin differed between adolescents with and without allergy symptoms. In regression models IgE was significantly associated with inadequate sleep duration and leptin with weight status.
Excess weight and inadequate sleep duration are independently associated with the incidence of allergy symptoms in adolescents. Adequate sleep duration and weight during adolescence might be relevant for a decreased risk of suffering allergy symptoms.
BMC Public Health 01/2014; 14(1):19. DOI:10.1186/1471-2458-14-19 · 2.26 Impact Factor
"This psychoactive drug blocks histamine H1 receptors in the brain and often results in sleepiness and psychomotor disturbances (Tashiro et al., 2008). Not surprisingly, approximately 2–6 mg of chlorpheniramine has been shown to delay psychomotor responses and impair driving performance (Boyle et al., 2006; Tashiro et al., 2008; Van Ruitenbeek et al., 2008; Verster and Volkerts, 2004). Such side effects could be the cause or a factor in accidents and road traffic injury (Cimbura et al., 1982; Sen et al., 2007; Skegg et al., 1979; Woratanarat et al., 2009). "
[Show abstract][Hide abstract] ABSTRACT: This study aimed to evaluate the effects of chlorpheniramine on psychomotor performance and the counteracting effects of caffeine on those sedative antihistamine actions. Sixteen healthy young men participated in this study. Using a double-blind placebo-controlled crossover design, each subject was administered one of the following conditions in a random order with a one-week interval: 'placebo-placebo', '4 mg of chlorpheniramine-placebo', 'placebo-200 mg of caffeine' or '4 mg of chlorpheniramine-200 mg of caffeine'. Before and after the treatments, psychomotor functions were assessed using a battery of tests. Additionally, subjective responses were assessed using a visual analogue scale (VAS). Psychomotor performance changed over time in different ways according to the combination of study medications. In the 'chlorpheniramine-placebo' condition, reaction times of the compensatory tracking task were significantly impaired compared with the other three conditions. In addition, the number of omission errors of the continuous performance test were significantly greater compared with the 'placebo-caffeine' condition. However, the response pattern of the 'chlorpheniramine-caffeine' condition was not significantly different from that of the 'placebo-placebo' condition. Changes of VAS for sleepiness were significantly greater in the 'chlorpheniramine-placebo' condition compared with the other three conditions. In conclusion, chlorpheniramine significantly increases subjective sleepiness and objectively impairs psychomotor performance. However, caffeine counteracts these sedative effects and psychomotor impairments.
Journal of Psychopharmacology 06/2012; 27(1). DOI:10.1177/0269881112450784 · 3.59 Impact Factor
"When taken at night, first-generation H1-antihistamines increase the
latency to the onset of rapid eye movement sleep and reduce the duration of rapid
eye movement sleep[19-21]. The residual effects of poor sleep, including impairment
of attention, vigilance, working memory, and sensory-motor performance, are still
present the next morning[20,22]. The detrimental central nervous system
effects of first-generation H1-antihistamines on learning and examination
performance in children and on impairment of the ability of adults to work, drive,
and fly aircraft have been reviewed in detail in a recent review. "
[Show abstract][Hide abstract] ABSTRACT: This article reviews the molecular biology of the interaction of histamine with its H1-receptor and describes the concept that H1-antihistamines are not receptor antagonists but are inverse agonists i.e. they produce the opposite effect on the receptor to histamine. It then discourages the use of first-generation H1-antihistamines in clinical practice today for two main reasons. First, they are less effective than second generation H1-antihistamines. Second, they have unwanted side effects, particularly central nervous system and anti-cholinergic effects, and have the potential for causing severe toxic reactions which are not shared by second-generation H1-antihistamines. There are many efficacious and safe second-generation H1-antihistamines on the market for the treatment of allergic disease. Of the three drugs highlighted in this review, levocetirizine and fexofenadine are the most efficacious in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals while fexofenadine has a relatively short duration of action requiring twice daily administration for full all round daily protection. While desloratadine is less efficacious, it has the advantages of rarely causing somnolence and having a long duration of action. Lastly, all H1-antihistamines have anti-inflammatory effects but it requires regular daily dosing rather than dosing ‘on-demand’ for this effect to be clinically demonstrable.
World Allergy Organization Journal 02/2011; 4(3):S22-S27. DOI:10.1097/WOX.0b013e3181f385d9