Driving Impairment and Altered Ocular Activity Under the Effects of Alprazolam and Alcohol: A Randomized, Double-blind, Placebo-controlled Study

Background: Alprazolam, also known by trade-name Xanax, is regularly detected along with alcohol in blood samples of drivers injured or killed in traffic collisions. While their co-consumption is principally legal, policy guidelines concerning fitness-to-drive are lacking and methods to index impairment are underdeveloped.

Methods: In this randomized, double-blind, placebo-controlled, crossover trial, we examined whether legally permissible levels of alcohol [target 0.04% blood alcohol concentration (BAC)], alprazolam (1mg), and their combination impacts driving performance, and whether driving impairment can be indexed by ocular activity. Participants completed a test battery consisting of a 40-minute simulated highway drive with ocular parameters assessed simultaneously, the Karolinska Sleepiness Scale, and a confidence to drive assessment following four separate treatment combinations. The predictive efficacy of ocular parameters to identify alcohol and alprazolam-related driving impairment was also examined.

Results: Among 21 healthy, fully licensed drivers (37% female, mean age 28.43, SD ± 3.96), driving performance was significantly impacted by alprazolam, alcohol, and their combination. Linear regression models revealed that the odds of an out-of-lane event occurring increased five-fold under the influence alprazolam alone and when combined with alcohol. An increase in gaze transition entropy (GTE) demonstrated the strongest association with the odds of an out-of-lane event occurring in the same minute, with both microsleeps and fixation rate achieving moderate accuracy across treatments.

Conclusions: Alprazolam and alcohol, alone and in combination, impaired select aspects of vehicle control over time. GTE, microsleeps, and fixation rate show potential as real-time indicators of driving impairment and crash risk associated with alcohol and alprazolam consumption.