PROBING DRUG RELATED MENTAL DISORDERS OF AGING

探索与药物相关的衰老精神障碍

• 批准号: 2750713
• 负责人: IRA R KATZ
• 金额: $ 44.13万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750713
• 关键词: aging; antihypercholesterolemic agent; antihyperlipoproteinemic agent; behavior disorders; behavioral /social science research tag; clinical research; cognition disorders; comorbidity; disease /disorder etiology; drug adverse effect; drug interactions; geriatrics; human old age (65+); human subject; mood disorders; naproxen; psychopharmacology; sertraline

Adverse effects of medications prescribed for elderly patients are common causes of the mental disorders of aging. Therefore, studies of the cognitive, affective, and behavioral symptoms that result from the administration of centrally-acting medications can provide information about the symptoms that characterize the toxic encephalopathies. From a practical perspective, they can provide clinicians and patients with information on the risks associated with use of the tested medications that could facilitate the prevention of disability. Accordingly, we are proposing to conduct randomized, double-blind, placebo-controlled challenge studies in which we will administer commonly prescribed medications for a period of several weeks to healthy, medically stable elderly volunteers. We will test for effects of active medications versus placebo with weekly tests of cognition, depression, other mood states, and sleepiness/alertness, and with daily self-reports of events and of both positive and negative affects. The medications to be studied were selected because they are commonly used, sufficiently safe to allow administration to elderly volunteers, and are suspected as causes of cognitive or affective toxicity. We propose two studies: Study I will compare the effects of 5 weeks of metoclopramide (up to 40 mg/day), sertraline (up to 200 mg/day), naproxen (up to 1000 mg/day), and placebo. Study II will compare 14 weeks of simvastatin (up to 20 mg/day) with placebo. Analyses will include modeling using random regression models. The hypotheses to be tested are that the medications under investigation can cause behavioral toxicity manifest by changes in cognitive performance assessed through weekly assessments; depressive or related symptoms manifest through weekly clinical interviews or self- reports on depression and behavioral rating scales; and increased negative affect and/or decreased positive affect as assessed through daily self-reports. We will also explore the impact of medications on daily reports of positive or negative events and on the relationship between daily events and daily affect.

老年患者服用药物的不良反应是 衰老性精神障碍的常见原因。 因此，研究 由以下原因引起的认知、情感和行为症状 中枢作用药物的管理可以提供信息 关于中毒性脑病的特征症状。 从 从实用的角度来看，他们可以为临床医生和患者提供 有关使用受测药物的相关风险的信息 这可以促进残疾的预防。 据此，我们是 提议进行随机、双盲、安慰剂对照 挑战研究，我们将在其中进行常用处方 服用几周的药物以保持健康、病情稳定 老年志愿者。 我们将测试活性药物的效果 与安慰剂相比，每周测试认知、抑郁和其他情绪 状态、困倦/警觉性以及每日事件自我报告 以及积极和消极的影响。 所要服用的药物 选择研究的原因是它们常用、足够安全 允许对老年志愿者进行管理，并被怀疑 认知或情感毒性的原因。 我们提出两项研究： 研究 I 将比较甲氧氯普胺 5 周（最多 40 毫克/天）、舍曲林（高达 200 毫克/天）、萘普生（高达 1000 毫克/天）、 和安慰剂。 研究 II 将比较 14 周的辛伐他汀（最多 20 毫克/天）与安慰剂。 分析将包括使用随机模型进行建模 回归模型。 要检验的假设是药物 正在调查中可能会导致行为毒性，并通过变化表现出来 通过每周评估评估认知表现；抑郁的 或通过每周临床访谈或自我检查表现出相关症状 关于抑郁症和行为评级量表的报告；并增加了 通过评估负面影响和/或减少的积极影响 每日自我报告。 我们还将探讨药物对 积极或消极事件以及关系的每日报告 日常事件和日常情感之间。