Antihistamines and Driving-Related Behavior: A Review of the Evidence for Impairment

Moskowitz, Herbert, 1925- · 2004 · ROSA P / United States. Department of Transportation. National Highway Traffic Safety Administration

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Summary

This report reviews the scientific literature regarding the effects of antihistamines (H1-receptor antagonists) on driving-related skills and behavior. Motivated by traffic safety concerns over the widespread use of these medications, particularly their potential to cause sedation and central nervous system dysfunction, the study aims to evaluate the impairment risks associated with first-generation versus second-generation antihistamines. While epidemiological data suggests a slight, ambiguous link between antihistamine use and crash rates, the authors note significant limitations in such studies, including small sample sizes and lack of control groups. Consequently, the review focuses primarily on experimental studies that allow for controlled assessment of drug effects on performance. The methodology involved a comprehensive search of bibliographic databases, identifying 130 publications from 1998 and earlier that met strict inclusion criteria. These studies involved healthy human subjects or allergy patients, included placebo controls, and measured driving-related performance tasks. The analysis focused on ten specific drugs: five first-generation agents (chlorpheniramine, clemastine, diphenhydramine, hydroxyzine, and tripolidine) and five second-generation agents (astemizole, cetirizine, fexofenadine, loratadine, and terfenadine). Results were coded for significant impairment across ten behavioral categories, including driving/piloting, psychomotor skills, perception, cognitive tasks, divided attention, vigilance, tracking, reaction time, and physiological measures of sedation. The findings indicate overwhelming evidence that first-generation antihistamines produce objective signs of skills performance impairment and subjective symptoms of sedation. In contrast, second-generation antihistamines generally represent a significant reduction in side effects; however, the review concludes that some evidence remains suggesting that even second-generation drugs may cause sedation and objective skills impairment in certain cases or for specific individuals. There is considerable variation in impairment levels within both drug generations, indicating that some drugs are safer than others regarding driving performance. Additionally, the review highlights that methodological sensitivity varies across different testing techniques, with some behavioral domains being more sensitive to antihistamine effects than others. The significance of this review lies in its confirmation that while second-generation antihistamines offer a superior benefit-risk profile compared to first-generation drugs, they are not entirely free of impairment risks. The authors conclude that future studies must utilize the most methodologically sound techniques to allow for better comparisons between drugs. The report underscores the importance of selecting specific antihistamines that minimize sedation and performance impairment for individuals who drive, pilot aircraft, or operate machinery, thereby informing clinical choices and traffic safety policies.

Key finding

First-generation antihistamines produce significant objective driving impairment and sedation, while second-generation drugs generally show reduced effects but still cause impairment in some individuals.

Methodology

review

Provenance

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Summary generated by qwen3.6-27b-prismaquant on 2026-06-10; verification: verified_with_issues.

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