Alprazolam and Simulated Driving Performance: Next Day Effects

摘要 年，醉酒驾驶以及相关的交通事故和死亡人数显著增加。 在过去的十年里，美国。而违禁药物占醉酒驾车的大部分 在某些情况下，有许多处方药也会损害驾驶能力。最令人担忧的是 在假定的治疗作用持续时间后可能损害驾驶能力的处方药。这 当FDA要求所有含有唑吡坦的催眠药物重新贴标签时，这一现象得到了突显 由于即使在8小时后也存在潜在损害药物的血液浓度；这种影响 严重程度上有性别上的差异。与男性相比，这种影响在女性中加剧。阿普唑仑股份 唑吡坦的许多药理特性和聚集的证据表明，它也可能导致 延长精神运动障碍，超过建议的治疗时间。这个项目提出了 一项研究招募了同等数量的男性和女性健康志愿者，他们将在6个晚上参加 评估阿普唑仑是否对认知或精神运动表现有负面影响 给药后早晨与阳性对照和阴性对照进行比较。在高度的 具有高外部效度的复杂驾驶模拟器将在服药前和服药后第二天早上进行测试 行政管理。这项随机双盲研究将测试阿普唑仑的三种治疗剂量，一种 潜在损害剂量的唑吡坦和安慰剂在混合因素设计中-每个受试者都接受所有 毒品状况。为了评估性行为是否会影响第二天的阿普唑仑效应，性行为将被分析为- 主体因素。拟议的实验将使用敏感的行为和分析评估来产生 关于阿普唑仑以前未被探索的性质的定量和定性数据。根据流行的情况 在美国的麻醉驾驶中，从这项研究中获得的模拟驾驶数据将具有重要意义 对公共健康和安全的影响。

ABSTRACT There has been a significant rise in drugged driving, and associated traffic accidents and fatalities, in the United States over the last decade. While illegal substances account for the majority of drugged–driving cases, there are a number of prescription medications that can also impair driving ability. Most concerning are the prescription drugs which may impair driving ability after the presumed duration of therapeutic action. This phenomenon was highlighted when the FDA mandated relabeling of all hypnotic drugs containing zolpidem due to the presence of potentially impairing blood concentrations of the drug even after 8 hours; an effect that had sex-specific in its severity. This effect was exacerbated in females compared to males. Alprazolam shares many pharmacological properties with zolpidem and converging evidence suggests it may also cause prolonged psychomotor impairment beyond the proposed therapeutic duration of action. This project proposes a study enrolling an equal number of male and female healthy volunteers who will participate in six overnight sessions to evaluate if alprazolam has a negative impact on cognitive or psychomotor performance the morning after administration compared to positive and negative controls. Performance on a highly sophisticated driving simulator with high external validity will be tested before and the morning after drug administration. This randomized, double-blind study will test three therapeutic doses of alprazolam, a potentially impairing dose of zolpidem, and placebo in a mixed-factorial design—with each subject receiving all drug conditions. To evaluate if sex influences next-day alprazolam effects, sex will be analyzed as a between- subjects factor. The proposed experiment will use sensitive behavioral and analytic assessments to yield quantitative and qualitative data on previously unexplored properties of alprazolam. In light of the prevalence of drugged driving in the United States, the simulated driving data obtained from this study will have significant public health and safety implications.