LONG-TERM LORAZEPAM USE AND ACUTE TOXICITY IN THE AGED

描述：苯二氮卓类（BZP）劳拉西泮广泛用于 治疗患有广泛性焦虑症（GAD）的老年人， 可能是这个人群中最常见的焦虑症劳拉西泮 通常推荐用于老年人的治疗，由于缺乏 与年龄相关的肝脏代谢和清除率显著降低。然而，在这方面， 急性劳拉西泮剂量已经显示出对言语产生有害影响， 记忆和姿势摇摆的增加，这与更大的 福尔斯的风险。急性剂量的劳拉西泮对记忆和 精神功能在劳拉西泮治疗21天后仍然存在。 在一项研究中，每名受试者都接受了他或她通常的早晨剂量的挑战。 此外，在长期BZP的主要年轻人群中， 治疗多年，通常单位剂量的急性BZP挑战已被 会导致严重的神经认知障碍这些研究表明 急性BZP剂量的不良性能影响可能持续存在， 经过长期治疗。流行病学研究也表明 老年人长期使用BZP，福尔斯和运动风险增加 车辆事故。然而，没有研究已经检查了急性 BZP对接受长期BZP治疗的老年患者的性能影响 治疗，以及可能影响治疗的各种因素。 对这些不良急性反应的敏感性。我们的研究表明 劳拉西泮的剂量，而不是血浆药物水平，影响急性 劳拉西泮慢性治疗3周后诱导的认知毒性。我们 也有初步数据表明，白色物质纤维组织，如 通过扩散张量成像（DTI）测量，可能会影响 在未经治疗的健康老年人中劳拉西泮诱导的急性损伤。但 这些因素对老年人急性绩效的影响程度 接受这种药物长期治疗的个人尚不清楚。 确定可能最强烈地导致有害物质的因素 劳拉西泮对记忆和姿势平衡的急性作用是理论上的， 临床利益，并可能指导临床实践，更安全地使用 劳拉西泮长期治疗老年广泛性焦虑症患者。的 拟议的研究旨在回答以下问题： 长期接受劳拉西泮治疗GAD的个体， 认知和心理表现存在有害影响，或 每日最高单位剂量给药后的姿势摇摆？这 主体因素（i.例如，最高每日单位剂量、每日总剂量 给药频率、治疗持续时间和脑白色物质指数 组织）对劳拉西泮的急性作用贡献最大， 认知/运动表现或姿势摇摆的老年人接受 劳拉西泮长期治疗广泛性焦虑症

DESCRIPTION: The benzodiazepine (BZP) lorazepam is widely utilized in the treatment of elderly individuals with Generalized Anxiety Disorder (GAD), probably the most common anxiety disorder in this population. Lorazepam is usually recommended for the treatment of the elderly due to the lack of significant age-related reduction in hepatic metabolism and clearance. However, acute lorazepam doses have been shown to produce deleterious effects on verbal memory and increases in postural sway, which has been associated with greater risk for falls. The adverse effects of acute doses of lorazepam on memory and psychomotor functioning are still present after 21 days of lorazepam treatment. In one study, each subject was challenged with his or her usual morning dose. Additionally, among predominantly younger populations on long-term BZP treatment for years, acute BZP challenges with the usual unit dose have been found to result in significant neurocognitive impairment. These studies suggest that the adverse performance effects of acute BZP doses may persist even following long-term treatment. Epidemiological studies have also linked long-term BZP use in the elderly with increased risk for falls and motor vehicle accidents. However, there are no studies that have examined the acute performance effects of BZP in elderly patients receiving long-term BZP treatment, and the various subject factors that may influence the susceptibility to these adverse acute effects. There is evidence from our study that the dose of lorazepam, but not the plasma drug levels, influences acute lorazepam-induced cognitive toxicity following chronic three-week treatment. We also have preliminary data suggesting that white matter fiber organization, as measured by diffusion tensor imaging (DTI), may influence the magnitude of lorazepam-induced acute impairment in untreated healthy elderly. However, the extent to which these factors influence acute performance effects among elderly individuals receiving long-term treatment with this medication is not known. Identifying the factors that may contribute most strongly to the deleterious acute effects of lorazepam on memory and postural balance is of theoretical and clinical interest, and may guide clinical practice in the safer use of lorazepam for the long-term treatment of elderly patients with GAD. The proposed study is designed to answer the following questions: Among elderly individuals on long-term treatment with lorazepam for GAD, what significant deleterious effects are present in cognitive and psychomotor performance or postural sway following administration of their highest daily Unit dose? Which subject factors (i. e., strength of highest daily Unit dose, total daily dose, frequency of dosing, duration of treatment, and an index of brain white matter organization) contribute most strongly to the acute effects of lorazepam on cognitive/motor performance or postural sway in elderly individuals receiving long-term lorazepam treatment for GAD?