LONG-TERM LORAZEPAM USE AND ACUTE TOXICITY IN THE AGED

老年人长期使用劳拉西泮和急性毒性

• 批准号: 6499284
• 负责人: Nunzio Pomara
• 金额: $ 26.65万
• 依托单位: NATHAN S. KLINE INSTITUTE FOR PSYCH RES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-10 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499284
• 关键词: aging; anxiety disorders; cognition; drug adverse effect; human old age (65+); human subject; lorazepam; mental disorder chemotherapy; patient oriented research; posture; psychological aspect of aging; psychomotor function

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?

描述：苯二氮(BZP)劳拉西潘广泛应用于 老年人广泛性焦虑障碍(GAD)的治疗， 可能是这个人群中最常见的焦虑症。劳拉西潘是 通常推荐用于治疗因缺乏营养不良的老年人 与年龄相关的肝脏代谢和清除量显著降低。然而， 急性剂量的劳拉西潘已被证明会对言语产生有害影响 记忆力和姿势摆动的增加，这与更大的 有跌倒的风险。急性剂量劳拉西潘对记忆和神经功能的不良影响 在劳拉西潘治疗21天后，精神运动功能仍然存在。 在一项研究中，每个受试者都接受了他或她通常早上服用的剂量的挑战。 此外，在长期服用BZP的主要是年轻人群中 治疗多年来，急性BZP挑战与通常的单位剂量 会导致严重的神经认知障碍。这些研究表明 急性剂量的BZP的不良影响甚至可能持续下去 经过长期治疗后。流行病学研究也将 长期服用BZP的老年人跌倒和运动风险增加 车祸。然而，目前还没有研究对急性呼吸道疾病进行研究 BZP对老年患者长期服用BZP的影响 治疗，以及可能影响治疗的各种主观因素。 对这些不利的急性影响的易感性。我们的研究有证据表明 劳拉西潘的剂量，而不是血浆药物浓度，会影响急性 劳拉西潘慢性治疗三周后引起的认知毒性。我们 也有初步数据表明白质纤维组织，如 通过弥散张量成像(DTI)测量，可能会影响 未经治疗的健康老年人中劳拉西潘所致的急性损伤。然而， 这些因素在多大程度上影响老年人的急性绩效 接受这种药物长期治疗的个人尚不清楚。 确定可能对有害因素起最大作用的因素 劳拉西潘对记忆和姿势平衡的急性影响是理论和 临床兴趣，并可能指导临床实践中更安全地使用 劳拉西潘用于长期治疗老年广泛性AD患者。这个 拟议的研究旨在回答以下问题：在老年人中 长期使用劳拉西潘治疗广泛性AD的患者，有什么意义？ 有害的影响存在于认知和精神运动表现或 服用最高每日单位剂量后的体位摆动？哪一个 受试者因素(例如，每日最高单位剂量的强度，每日总剂量， 给药频率、治疗时间和脑白质指数 组织)对劳拉西潘的急性影响贡献最大 接受治疗的老年人的认知/运动表现或姿势摆动 劳拉西潘长期治疗广泛性焦虑症？