LONGTERM LORAZEPAM USE AND ACUTE TOXICITY IN THE ELDERLY

老年人长期使用劳拉西泮和急性毒性

• 批准号: 7605694
• 负责人: Nunzio Pomara
• 金额: $ 0.47万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605694
• 关键词: Acute; Adverse effects; Anxiety Disorders; Benzodiazepines; Brain; Chronic; Clinical; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Daily; Data; Diffusion Magnetic Resonance Imaging; Dose; Elderly; Epidemiologic Studies; Fiber; Frequencies; Funding; Generalized Anxiety Disorder; Grant; Hepatic; Impairment; Individual; Institution; Link; Lorazepam; Measures; Memory; Metabolism; Motor; Musculoskeletal Equilibrium; Neurocognitive; Performance; Plasma; Population; Predisposition; Psychomotor Performance; Research; Research Design; Research Personnel; Resources; Risk; Source; Toxic effect; United States National Institutes of Health; Week; age related; day; falls; indexing; interest; older patient; treatment duration; vehicular accident; white matter

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Our group has demonstrated that the adverse effects of lorazepam on memory and psychomotor functioning are still present after 21 days of lorazepam treatment. In this study, each subject was challenged with his or her usual morning dose. Additionally, among predominantly younger population on long-term BZP treatment for years, acute BZP challenges of his or her usual morning 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 on 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 durg levels influence 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 on long-term treatment 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 serve to guide clinical practice in the safer use of lorazepam for the long-term treatment of elderly patients with GAD. The objectives of the proposed study are designed to answer the following questions: 1. Among elderly individuals on long-term treatment with lorazepam for GAD, what significant deleterious effects are present in terms of cognitive and psychomotor performance or postural sway following administration of their highest daily unit dose? 2. Which subject factors (i.e., strength of highest daily unit 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 on long-term lorazepam treatment for GAD?

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 苯二氮卓类药物（BZP），劳拉西泮，被广泛用于治疗老年广泛性焦虑症（GAD），可能是该人群中最常见的焦虑症。 劳拉西泮通常被推荐用于老年人的治疗，因为老年人的肝脏代谢和清除率没有明显的年龄相关性降低。然而，急性劳拉西泮剂量已被证明对语言记忆产生有害影响，并增加姿势摇摆，这与更大的福尔斯风险有关。 我们的小组已经证明，劳拉西泮对记忆和精神功能的不良影响在劳拉西泮治疗21天后仍然存在。 在本研究中，每例受试者均接受其常规早晨剂量的激发。 此外，在长期接受BZP治疗多年的主要年轻人群中，发现他或她通常早晨剂量的急性BZP挑战导致显著的神经认知障碍。 这些研究表明，即使在长期治疗后，急性BZP剂量的不良性能影响也可能持续存在。 流行病学研究也将老年人长期使用BZP与福尔斯和机动车事故的风险增加联系起来。 然而，尚无研究检查BZP对长期BZP治疗老年患者的急性性能影响以及可能影响对这些急性不良反应敏感性的各种受试者因素。 我们的研究有证据表明，劳拉西泮的剂量，而不是血浆杜尔格水平影响急性劳拉西泮诱导的认知毒性后，慢性三周的治疗。 我们也有初步的数据表明，白色物质纤维组织，通过扩散张量成像（DTI）测量，可能会影响未经治疗的健康老年人劳拉西泮诱导的急性损伤的程度。 然而，这些因素在多大程度上影响老年人长期治疗的急性性能效应尚不清楚。 确定可能导致劳拉西泮对记忆和姿势平衡的有害急性效应的最强烈因素具有理论和临床意义，并可用于指导临床实践，以更安全地使用劳拉西泮长期治疗老年GAD患者。 拟议研究的目标旨在回答以下问题： 1. 在长期接受劳拉西泮治疗GAD的老年人中，给予最高日单位剂量后，在认知和精神表现或姿势摇摆方面存在哪些显著的有害影响？ 2. 哪些主体因素（即，最高每日单位剂量的强度、给药频率、治疗持续时间和脑白色组织指数）对劳拉西泮对接受长期劳拉西泮治疗的老年人GAD的认知/运动表现或姿势摇摆的急性效应的贡献最大。