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Sensitivity to dose or blood levels of alprazolam in predicting driving impairment
Traffic Injury Prevention
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. 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 (1 mg), 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. 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. 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.
Background:
The COVID-19 pandemic has had a significant impact on public mental health. Therefore, monitoring and oversight of the population mental health during crises such as a panedmic is an immediate priority. The aim of this study is to analyze the existing research works and findings in relation to the prevalence of stress, anxiety and depression in the general population during the COVID-19 pandemic.
Method:
In this systematic review and meta-analysis, articles that have focused on stress and anxiety prevalence among the general population during the COVID-19 pandemic were searched in the Science Direct, Embase, Scopus, PubMed, Web of Science (ISI) and Google Scholar databases, without a lower time limit and until May 2020. In order to perform a meta-analysis of the collected studies, the random effects model was used, and the heterogeneity of studies was investigated using the I2 index. Moreover. data analysis was conducted using the Comprehensive Meta-Analysis (CMA) software.
Results:
The prevalence of stress in 5 studies with a total sample size of 9074 is obtained as 29.6% (95% confidence limit: 24.3-35.4), the prevalence of anxiety in 17 studies with a sample size of 63,439 as 31.9% (95% confidence interval: 27.5-36.7), and the prevalence of depression in 14 studies with a sample size of 44,531 people as 33.7% (95% confidence interval: 27.5-40.6).
Conclusion:
COVID-19 not only causes physical health concerns but also results in a number of psychological disorders. The spread of the new coronavirus can impact the mental health of people in different communities. Thus, it is essential to preserve the mental health of individuals and to develop psychological interventions that can improve the mental health of vulnerable groups during the COVID-19 pandemic.
: Alprazolam is one of the most widely prescribed benzodiazepines for the treatment of generalized anxiety disorder and panic disorder. Its clinical use has been a point of contention as most addiction specialists consider it to be highly addictive, given its unique psychodynamic properties which limit its clinical usefulness, whereas many primary care physicians continue to prescribe it for longer periods than recommended. Clinical research data has not fully shed light on its "abuse liability," yet it is one of the most frequently prescribed benzodiazepines. "Abuse liability" is the degree to which a psychoactive drug has properties that facilitate people misusing it, or becoming addicted to it, and is commonly used in the literature. We have replaced it in our manuscript with "misuse liability" as it reflects a more updated terminology consistent with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In this paper, we have reviewed alprazolam's indications for use, its effect on pregnant women, misuse liability, withdrawal syndrome, pharmacodynamic properties, and suggest better clinical prescription practice of alprazolam by presenting an indepth theory of its clinical effects with use and withdrawal.
Objective: The COVID-19 pandemic has created a stressful environment of fear, isolation, and economic instability. This study quantifies rates of self-reported increases in use of anxiety-related medications and sleep aids, and identifies demographic, health and psychosocial correlates during the initial stay-at-home period of the COVID-19 pandemic.
Methods: An online survey was administered to U.S. adults (n = 2,739), aged 18 and older, from April 14 to April 22, 2020 to assess self-reported change in anti-anxiety and sleep aid use during the stay-at-home protocols. Data were weighted to the US population for analysis.
Results: Weighted results indicate anti-anxiety and sleep aid medications increased for 35.7% and 41.2% of the population, respectively. Major depressive disorder (MDD), generalized anxiety disorder (GAD), and somatization disorder (SD) symptoms were associated with increased use of anti-anxiety medications. GAD and SD were associated with increased use of sleep aids. Perceived stress, quality of life, fatigue and concentration were associated with increased use of anti-anxiety medication and sleep aids.
Conclusions: These findings provide critical insights necessary in preparing for future outbreaks of similar magnitude. Developing policies to support economic and healthcare infrastructure is a necessary first step to ameliorating secondary health consequences from an infectious disease outbreak.
The anxiolytic triazolobenzodiazepine alprazolam was administered to six male patients, aged 26 to 46 years, with panic disorder or agoraphobia (with panic attacks) to assess clinical effects and steady-state pharmacokinetics following multiple dosing at three levels: 3.0 mg/d, 6.0 mg/d, and 9.0 mg/d. Multiple-dose kinetics of alprazolam were compared with alprazolam disposition after a 1.0-mg oral dose in the same patients. Kinetic variables after the single dose were very similar to those reported previously for healthy young male volunteers. Mean values were peak plasma concentration, 19 ng/mL; time of peak, 1.33 hours after dosage; elimination half-life, 10.0 hours; total oral clearance, 1.11 mL/min/kg. During multiple dosage, mean steady-state plasma concentrations (Css) was proportional to dosing rate, and steady-state clearance was independent of dosage. Clinical improvement was rapid, with the greatest decrement in symptoms at the 3-mg/d dosage, at a mean Css of 30 ng/mL. Further improvement was not seen at 6 mg/d (Css, 62 ng/mL), or at 9 mg/d (Css, 103 ng/mL). Side effects, however, were directly related to dosage and plasma level, and increased progressively in number at the 3-, 6-, and 9-mg/d dosage levels. Thus, the disposition of alprazolam in young male patients with panic disorder is essentially identical to that in healthy male volunteers of similar age. Alprazolam clearance is independent of dose and plasma concentration up to daily doses of at least 9 mg/d, with steady-state plasma level proportional to dosing rate.