Pharmacotherapy of Latelife Generalized Anxiety Disorder

描述（由申请方提供）：本R 01重新提交资料来自一名新的主要研究者，重点关注老年人的广泛性焦虑症（GAD），这是一个重要的公共卫生问题，因为该年龄组的GAD患病率和负担很高。然而，晚年广泛性焦虑症的治疗证据是不够的，这种疾病仍然在很大程度上治疗不足。本研究是一项为期12周的随机、双盲、安慰剂对照艾司西酞普兰研究，艾司西酞普兰是一种耐受性良好且对5-羟色胺转运蛋白（SERT）具有高度特异性的SSRI。我们将从初级保健实践中招募176名60岁及以上的受试者进行治疗。受试者将患有GAD，目前无重度抑郁症。这项研究将允许纳入常见于焦虑老年人的合并症，包括抑郁症。我们将检查症状反应。作为次要的探索性分析，我们将检查功能障碍和神经心理学指标的治疗相关变化。我们将根据SERT多态性对受试者进行基因分型，SERT多态性被认为是SSRI治疗结果的调节剂，我们将确定SERT中的等位基因变异是否有助于治疗反应的变异性。我们的第一个目标是证明SSRI在初级保健部门对晚期GAD的疗效。我们期望在这一人群中证明药物疗效（以及结果的传播）将导致这种疾病的药物治疗利用率增加。疗效评价将包括检查治疗后的功能和神经心理学改善。第二个目标是检查治疗反应的遗传调节剂-这样的发现不仅可以改善晚年GAD治疗的个体化，而且可以更好地理解这种疾病的异质性的神经生物学来源。

DESCRIPTION (provided by applicant): This R01 resubmission from a new principal investigator focuses on generalized anxiety disorder (GAD) in elderly persons, a significant public health issue because of the high prevalence and burden of GAD in this age group. However, the treatment evidence in late life GAD is inadequate, and the illness remains vastly under treated. This study is a 12 week randomized, double-blind, placebo-controlled examination of escitalopram, an SSRI that is well-tolerated and highly specific for the serotonin transporter (SERT). We will recruit 176 subjects aged 60 and older from primary care practices for treatment. Subjects will have GAD without current major depressive disorder. The study will allow inclusion of comorbidity commonly seen in anxious elderly, including depression. We will examine symptomatic response. As secondary, exploratory analyses, we will examine treatment-attributable changes in functional disability and neuropsychological measures. We will genotype subjects in terms of a SERT polymorphism which has been posited as a moderator of SSRI treatment outcome, and we will determine whether allelic variation in the SERT contributes to the variability of treatment response. Our first goal is to demonstrate SSRI efficacy for late life GAD in the primary care sector. It is our expectation that demonstration of medication efficacy in this population (and dissemination of the results) would lead to increased utilization of pharmacotherapy for this disorder. Efficacy evaluation will include examination of functional and neuropsychological improvements from treatment. The second goal is the examination of a genetic moderator of treatment response - such findings could lead not only to improvements in the individualization of treatment for late life GAD, but also to a greater understanding of the neurobiological sources of heterogeneity in this disorder.