Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study

Blair Aitken; Amie C Hayley; Talitha C Ford; Lauren Geier; Brook A Shiferaw; Luke A Downey

doi:10.1016/j.drugalcdep.2023.110919

Driving impairment and altered ocular activity under the effects of alprazolam and alcohol: A randomized, double-blind, placebo-controlled study

Drug Alcohol Depend. 2023 Oct 1:251:110919. doi: 10.1016/j.drugalcdep.2023.110919. Epub 2023 Aug 8.

Authors

Blair Aitken¹, Amie C Hayley², Talitha C Ford³, Lauren Geier⁴, Brook A Shiferaw⁵, Luke A Downey⁶

Affiliations

¹ Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia.
² Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia; Institute for Breathing and Sleep (IBAS), Austin Hospital, Heidelberg, Victoria, Australia.
³ Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia; Cognitive Neuroscience Unit, Deakin University, Geelong, Victoria, Australia.
⁴ Forensic Science South Australia, Adelaide, Australia.
⁵ Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia; Institute for Breathing and Sleep (IBAS), Austin Hospital, Heidelberg, Victoria, Australia; Seeing Machines, Fyshwick, Australian Capital Territory (ACT), Australia.
⁶ Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, Victoria, Australia; Institute for Breathing and Sleep (IBAS), Austin Hospital, Heidelberg, Victoria, Australia. Electronic address: ldowney@swin.edu.au.

PMID: 37611483
DOI: 10.1016/j.drugalcdep.2023.110919

Abstract

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.

Keywords: Alcohol; Alprazolam; Driving; Gaze entropy; Ocular monitoring; Road safety.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Accidents, Traffic
Adult
Alprazolam* / pharmacology
Automobile Driving*
Blood Alcohol Content
Double-Blind Method
Ethanol / adverse effects
Female
Humans
Male

Substances

Alprazolam
Blood Alcohol Content
Ethanol