Antihistamines and driving-related behavior: A review of the evidence for impairment.

A review of the scientific literature concerning the effects of antihistamines on driving-related skills was conducted. After reviewing all pertinent publications from 1998 and earlier, a total of 130 publications were found to meet criteria for inclusion in the data summaries. A data base was created with study results being indexed, and summarized, by specific drug, dose, dosing schedule (i.e., single versus repeated) and H1-antagonist generation as well as by behavioral area or subjective measure. For each H1-antagonist generation, five drugs were evaluated: chlorpheniramine, clemastine, diphenhydramine, hydroxyzine and tripolidine for the 1 st-generation, and astemizole, cetirizine, fexofenadine, loratadine and terfenadine for the 2 nd-generation. It was concluded that: 1. There is some slight, but ambiguous, evidence from epidemiological studies of a connection between antihistamine use and traffic collision rates. However, these studies were done primarily when use of only 1st-generation (but not 2 nd-generation) antihistamines was prevalent; thus, more study is needed. 2. There is overwhelming evidence from the experimental literature that the 1 st-generation antihistamines produce objective signs of skills performance impairment as well as subjective symptoms of sedation. 3. While 2 nd-generation antihistamines represent a major triumph for the pharmaceutical industry in reducing potential side effects, there still remains some evidence that all antihistamines, even the 2 nd-generation drugs, may cause sedation and objective skills impairment at least in some cases and for some individuals. 4. Within both the 1 stand 2 nd-generation antihistamine groupings, there is considerable variation in objective evidence of impairment and in subjective effects such as sedation. Thus, there clearly are drugs that are to be preferred for use to avoid side effects such as sedation and driving-related performance impairment. 5. Methodologically, it is apparent that among the many diverse techniques for investigating driving-related impairment, some methods and behavioral domains are more sensitive to the effects of antihistamines. Future studies of antihistamines, therefore, must utilize the most methodologically-sound techniques so as to permit a better comparison between different drugs.