Evaluation of simulated driving in comparison to laboratory-based tests to assess the pharmacodynamics of alprazolam and alcohol

Huizinga, Coen R.H.; Zuiker, Rob; Kam, Marieke L. de; Ziagkos, Dimitrios; Kuipers, Jorrit; Mejia, Yuri; Gerven, Joop Ma van; Cohen, Adam F.

doi:10.1177/0269881119836198

Cited by 13 publications

(34 citation statements)

References 34 publications

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“…All data used in the present study were collected during two previous studies (Huizinga et al 2019;Koopmans et al 2020). In both studies subjects were healthy adults who were in possession of a valid drivers license.…”

Section: Data Collection For the Modelmentioning

confidence: 99%

“…Subsequently, this model was used to demonstrate sleepdeprived driving characteristics in subjects after intake of alprazolam or alcohol. The effect of alprazolam and alcohol on driving was previously studied in our institution by Huizinga et al (2019). (Huizinga et al 2019) In short, this was a single-center, randomized, double-blind, doubledummy, placebo-controlled, four-way crossover-study on alcohol and alprazolam in 24 healthy subjects (12 males, 12 females, age range 20-43 years), while performing neurocognitive and psychomotor tests on the NeuroCartV Ra comprehensive battery that can test all functional domains of the central nervous system (CNS)and a driving simulator (Green Dino BV, Wageningen, The Netherlands).…”

Section: Data Collection For the Modelmentioning

confidence: 99%

“…The effect of alprazolam and alcohol on driving was previously studied in our institution by Huizinga et al (2019). (Huizinga et al 2019) In short, this was a single-center, randomized, double-blind, doubledummy, placebo-controlled, four-way crossover-study on alcohol and alprazolam in 24 healthy subjects (12 males, 12 females, age range 20-43 years), while performing neurocognitive and psychomotor tests on the NeuroCartV Ra comprehensive battery that can test all functional domains of the central nervous system (CNS)and a driving simulator (Green Dino BV, Wageningen, The Netherlands). The interventions consisted of intravenously administered alcohol to obtain steady state concentrations of 0.5 g L À1 and 1.0 g L À1 , oral administration of 1 g alprazolam, or placebo (Zoethout et al 2012).…”

Section: Data Collection For the Modelmentioning

confidence: 99%

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Using machine learning techniques to characterize sleep-deprived driving behavior

Wall

Doll

Koopmans

et al. 2021

Traffic Injury Prevention

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Objective: Sleep deprivation is known to affect driving behavior and may lead to serious car accidents similar to the effects from e.g., alcohol. In a previous study, we have demonstrated that the use of machine learning techniques allows adequate characterization of abnormal driving behavior after alprazolam and/or alcohol intake. In the present study, we extend this approach to sleep deprivation and test the model for characterization of new interventions. We aimed to classify abnormal driving behavior after sleep deprivation, and, by using a machine learning model, we tested if this model could also pick up abnormal driving behavior resulting from other interventions. Methods: Data were collected during a previous study, in which 24 subjects were tested after being sleep-deprived and after a well-rested night. Features were calculated from several driving parameters, such as the lateral position, speed of the car, and steering speed. In the present study, we used a gradient boosting model to classify sleep deprivation. The model was validated using a 5-fold cross validation technique. Next, probability scores were used to identify the overlap of driving behavior after sleep deprivation and driving behavior affected by other interventions. In the current study alprazolam, alcohol, and placebo are used to test/validate the approach. Results: The sleep deprivation model detected abnormal driving behavior in the simulator with an accuracy of 77 ± 9%. Abnormal driving behavior after alprazolam, and to a lesser extent also after alcohol intake, showed remarkably similar characteristics to sleep deprivation. The average probability score for alprazolam and alcohol measurements was 0.79, for alcohol 0.63, and for placebo only 0.27 and 0.30, matching the expected relative drowsiness. Conclusion:We developed a model detecting abnormal driving induced by sleep deprivation. The model shows the similarities in driving characteristics between sleep deprivation and other interventions, i.e., alcohol and alprazolam. Consequently, our model for sleep deprivation may serve as a next reference point for a driving test battery of newly developed drugs.

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Section: Data Collection For the Modelmentioning

confidence: 99%

Section: Data Collection For the Modelmentioning

confidence: 99%

Section: Data Collection For the Modelmentioning

confidence: 99%

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Using machine learning techniques to characterize sleep-deprived driving behavior

Wall

Doll

Koopmans

et al. 2021

Traffic Injury Prevention

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“…Prior work shows that even young people demonstrate benzodiazepine-related decrements in a broad array of neurocognitive functions, with psychomotor speed prominently affected to a degree beyond that attributed to sedation alone (Fluck et al, 1998; Loring et al, 2012; Pomara et al, 2015). Accordingly, benzodiazepines have been found to diminish simulated driving performance (Huizinga et al, 2019), double the risk of motor vehicle accidents (Thomas, 1998 ) , and increase fall risk in older adults (Diaz-Gutierrez et al, 2017). However, the practicing clinician who prescribes these medications does not have a clinical means to determine whether their medical decision has influenced subtle changes.…”

Section: Introductionmentioning

confidence: 99%

A clinical method of evaluating simple reaction time and reaction accuracy is sensitive to a single dose of lorazepam

et al. 2020

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Rationale: Benzodiazepines are useful and commonly prescribed. Unfortunately, they are associated with subtle but functionally significant neurocognitive side effects that increase the risk of motor vehicle accidents and falls. Objective: The objective of this study was to determine whether clinically feasible measures of simple reaction time and reaction accuracy are sensitive to a single dose of lorazepam. Methods: Using a randomized, double-blind, crossover design, 26 healthy adults (13 women; age = 26.9 ± 8.2 yr) were given 1.0 mg lorazepam or placebo 90 minutes prior to two data collection sessions. Participants completed simple and reaction accuracy tasks using a standardized “ruler drop” testing paradigm during each session. Outcomes were mean and variability of simple reaction time and reaction accuracy, which evaluates a participant’s ability to catch the device solely on the random 50% of trials that lights affixed to it illuminate on release. Reaction accuracy requires a go/no-go decision within 420 ms before the falling device strikes the floor. Results: As compared with placebo, lorazepam increased simple reaction time variability (range = 43 ± 18 vs. 60 ± 23 ms, respectively; p = 0.004 and standard deviation = 14.6 ± 5.7 vs. 19.7 ± 7.3 ms, respectively; = 0.006) and decreased reaction accuracy (90 ± 7% vs. 84 ± 11%, respectively; p = 0.010). Conclusion: Given prior work demonstrating associations between simple reaction time and reaction accuracy and functional outcomes such as self-protection, response to perturbations, and fall risk, these clinically available measures may have a role in identifying subtle, functionally significant cognitive changes related to short-term benzodiazepine use.

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“…For impairment regarding both reaction time and impulsivity, increase in crash risk is expected (Fillmore et al 2008;Christoforou et al 2013). Different laboratory tests are also shown to be relevant for driving, as measured by standard deviation of lateral position (Huizinga et al 2019).…”

Section: Introductionmentioning

confidence: 99%

A comparison of driving related skills impaired by ethanol and zopiclone

Høiseth

Hjelmeland

Mørland

2020

Traffic Injury Prevention

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Objective: Ethanol and zopiclone are both sedating drugs that impair traffic relevant skills, but that show vast differences in epidemiological traffic risk. One explanation for this could be that they impair various kinds of skills differently, but this is less previously studied. The aim of this study was to compare effects of zopiclone and ethanol on a large battery of computerized psychomotor and cognitive tests according to different test classifications. Methods: Ethanol (50 grams), zopiclone 5 mg, zopiclone 10 mg or placebo was administered in a randomized trial with a cross-over design. Blood was sampled nine times after administration and analyzed for zopiclone and ethanol using fully validated methods. The computerized tests Connors Continuous Performance Test (CPT), Stockings of Cambridge (SOC) and choice reaction time (CRT) was performed at baseline and after administration. The three tests yielded fifteen different test components, which were categorized according to the three well-known behavior levels (automative behavior, control behavior and executive planning). Secondly, they were categorized into tests measuring "reaction time", "impulsivity" and "attention/cognition". Results: On all tests belonging to behavior level 1 and on all tests measuring "reaction time", more subjects were impaired by zopiclone than ethanol. On all tests measuring "impulsivity", more subjects were impaired by ethanol than zopiclone. Conclusion: Zopiclone and ethanol both lead to impairment, but have a different profile on what kind of tests and neurocognitive functions they mostly impair. This could be important in the understanding of the differences in traffic risk connected to these two drugs.

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Evaluation of simulated driving in comparison to laboratory-based tests to assess the pharmacodynamics of alprazolam and alcohol

Cited by 13 publications

References 34 publications

Using machine learning techniques to characterize sleep-deprived driving behavior

Using machine learning techniques to characterize sleep-deprived driving behavior

A clinical method of evaluating simple reaction time and reaction accuracy is sensitive to a single dose of lorazepam

A comparison of driving related skills impaired by ethanol and zopiclone

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