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Internal Medicine World Report
January 2005

Newer Antihistamines May Cause Cognitive Impairment at High Doses

Newer Antihistamines May Cause Cognitive Impairment at High Doses

By John Schieszer

Physicians are generally told that second-generation antihistamines are causing less cognitive impairment than the first-generation agents, but some of the newer medications may produce impairment if used at or above the recommended doses. In fact, according to new data presented at the American College of Allergy, Asthma & Immunology meeting, fexofenadine (Allegra) was suggested to be the only antihistamine not causing sedation among these antihistamines.

Overall, second-generation, nonsedating antihistamines have a lower tendency to cross the blood-brain barrier and thus cause fewer central nervous system side effects than their first-generation counterparts. However, researchers have cautioned that there are differences among the second-generation agents in their effects on cognitive function.

“Even though these are all second-generation antihistamines, it doesn’t mean they all have no sedation, and physicians need to be aware of these kinds of side effects when prescribing these types of medications,” said Dennis Spangler, MD, lead author and cochair of the allergy division of Children’s Health Care, Atlanta, Ga, and past president of the American Association of Certified Allergists.

Dr Spangler and colleagues conducted a MEDLINE search of randomized, placebo-controlled studies analyzing cognitive impairment in trials involving second-generation antihistamines. The meta-analysis included 43 studies with objective assessment parameters (ie, driving performance, critical flicker confusion, and divided attention tasks).

“We found that fexofenadine had the lowest incidence of any side effects of the central nervous system, including sedation and/or effects. We also found that almost all the other drugs had several studies that did show sedation,” said Dr Spangler.

However, he noted that there was a wide variation in the number of available, well-designed studies. The most rigorously assessed agents were cetirizine (Zyrtec) and fexofenadine. Several agents, including acrivastine (Semprex-D) and loratadine (Claritin), were found as not impairing cognitive function at recommended doses but impairing at higher-than recommended doses.

The newer antihistamines, desloratadine (Clarinex) and levocetirizine (Xyzal) did not produce cognitive impairment at recommended doses (5 mg once/day); however, neither drug was investigated at higher doses.

Results for cetirizine were mixed, although cognitive impairment at ³10 mg (recommended dose, 5 or 10 mg once/day) was seen in a number of studies. In comparison, fexofenadine was shown nonimpairing in several studies, even in doses up to 360 mg (recommended dose, 60 mg twice daily), with 1 exception—one study showed cognitive impairment in critical tracking with the first doses (120 or 180 mg) but not with subsequent doses.

“If you look at the information distributed to doctors, there is the insinuation that all second-generation antihistamines are nonsedative. But our study shows that there are studies that show a good number of the second-generation antihistamines do have sedation, and you need to take that into consideration when prescribing these medications,” said Dr Spangler.

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