PROBING DRUG RELATED MENTAL DISORDERS OF AGING

为老年患者处方的药物的不良反应是 老年精神障碍的常见原因。 因此，研究 认知，情感和行为症状，导致从 中枢作用药物的给药可以提供 中毒性脑病的症状 从 从实用的角度来看，它们可以为临床医生和患者提供 与使用试验药物相关的风险信息 这将有助于预防残疾。 因此，我们 建议进行随机、双盲、安慰剂对照 挑战性研究中，我们将管理通常规定 几周的药物治疗，以健康，医学稳定 老年志愿者 我们将测试活性药物的作用 与安慰剂相比，每周进行认知、抑郁、其他情绪测试 状态和嗜睡/警觉性，以及每日自我报告事件 积极和消极的影响。 这些药物将 选择这些研究是因为它们是常用的，足够安全， 允许老年志愿者服用，并被怀疑是 认知或情感毒性的原因。 我们提出两项研究： 研究I将比较5周甲氧氯普胺（最多40 100 mg/天），舍曲林（高达200 mg/天），萘普生（高达1000 mg/天）， 和安慰剂。 研究II将比较14周的辛伐他汀（最多20周） mg/天）。 分析将包括使用随机 回归模型 有待检验的假设是， 可能导致行为毒性，表现为 通过每周评估评估认知表现;抑郁 或相关症状通过每周临床访谈或自我- 抑郁症和行为评定量表的报告; 消极影响和/或积极影响减少， 每日自我报告 我们还将探讨药物对 积极或消极事件的日常报告以及 日常事件和日常情绪之间的联系

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.