Road traffic crash risk associated with prescription of hydroxyzine and other sedating H1-antihistamines: A responsibility and case-crossover study

Background: H1 antihistamines differ from each other by their ability to cross the blood-brain barrier. The resulting sedating effect can be sought in therapy but may be a driving hazard. The aim of this study was to estimate the impact of sedating H1-antihistamines on the risk of road traffic crash, with a particular focus on hydroxyzine which is also indicated as an anxiolytic in France.

Methods: The study consisted in extracting and matching data from three French nationwide databases: the national healthcare insurance database, police reports and the police national database of injurious crashes. All sedating H1-antihistamines, including hydroxyzine, were considered in the study. A case-control analysis, in which responsible drivers were cases and non-responsible were controls was performed. A case-crossover analysis, comparing for the same subject exposure during a period immediately before the crash with exposure during an earlier period, was also conducted.

Results: The extraction and matching procedures over the July 2005-December 2011 period led to the inclusion of 142,771 drivers involved in an injurious road traffic crash. The responsibility study found an increased risk of being responsible for an injurious road traffic crash in hydroxyzine users who were registered with a long-term chronic disease (mostly psychiatric disorders) on the day of the crash (OR=1.67 [1.22-2.30]). Among them, the risk was even higher in drivers with highest exposure levels (OR=2.60 [1.23-5.50]). There was no impact of sedating H1 antihistamine treatment initiation on the risk of crash.

Conclusion: Even if it is difficult to disentangle the part of the increased risk that would be causally related to hydroxyzine and the part related to behaviours of patients with a heavy psychiatric disorder, our study raises the alarm on the crash risk linked to hydroxyzine utilization in countries in which the anxiolytic indication is widespread.