Effects of second generation antihistamines on daily driving with and without subtasks measured in a driving simulator

Second-generation antihistamines are widely used for the management of allergic conditions. In addition, many second-generation antihistamines are readily available over the counter at pharmacies. However, the effects of these medications on driving performance when subtasks are involved remain unclear. This study investigated the impact of second-generation antihistamines—known for their reduced sedative effects compared with first-generation antihistamines—on driving performance. Specifically, we aimed to quantify the class-level effect of second-generation antihistamines on driving performance under everyday conditions—including periods with and without conversational subtasks—and to test whether performance decrements are greater during subtask than non-subtask periods. Participants (N = 21; mean age 34.6 ± 7.73 years) completed a driving-simulator task under four within-subject conditions (2 × 2): with vs. without a subtask and while taking vs. not taking a second-generation antihistamine (fexofenadine, bepotastine, levocetirizine, ketotifen, or desloratadine). Driving performance was assessed across six predefined events under each condition. The findings revealed that, on average, the class-level effect of second-generation antihistamines on driving performance was minimal, regardless of the driving events. However, although statistical significance was not reached, the data showed a consistent trend suggesting that performing subtasks while taking second-generation antihistamines may increase driving risk across all events. At the class level, second-generation antihistamines exert minimal effects on overall driving performance; nevertheless, concurrent subtasks (e.g., conversation) may diminish safety margins. While not definitive, these exploratory findings support heightened caution during everyday multitasking and motivate larger, sex-balanced studies to confirm and characterize medication–subtask interactions. Many drivers use second-generation antihistamines, but their effects during multitasking in daily driving were unclear. Our results suggest that, as a class, these drugs do not impair everyday driving averaged across subtasks that appear and disappear. Although not statistically significant, we observed a consistent trend that subtasking while taking second-generation antihistamines may increase driving risk.