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.
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