• change from baseline in HAM-A total score [ Time Frame: nine weeks from baseline ] [ Designated as safety issue: No ]
  

Generalized anxiety disorder (GAD) is a serious and distinct illness that occurs in significant numbers, affecting at least 7 million people in the United States alone. The prevalence of GAD is higher in the primary care setting with rates twice as high as the rates reported in community samples. GAD is a life-long disorder with low remission rates, resulting in high disability and morbidity. Of significance are emerging epidemiological data suggesting that GAD is highly prevalent in the geriatric population with prevalence rates ranging from 1.9% to 7.1% and accounting for the majority of anxiety disorder cases in this age group. More alarming is the fact that the presence of anxiety symptoms leads to considerable functional impairment, increased morbidity, and mortality among the affected elderly population, thus leading to increases in the costs of their care. However, despite advances made in GAD treatment in the adult population, no prospective data are presently available on the treatment of GAD in the elderly population, forcing clinicians to provide treatment without the guidance of scientific data. These findings are of particular relevance to the Veterans Affairs Health Care System where the average age of patients treated in primary care clinics is currently 60-64 years. The present application focuses on this target subpopulation of elderly veterans.

This proposal aims to provide evidence-based guidelines for pharmacological management of elderly veterans suffering from generalized anxiety disorder. This will be accomplished by conducting a clinical trial in elderly veterans suffering from GAD by evaluating the efficacy and safety of sertraline - a proven anxiolytic compound widely used in the young adult population.

We believe that this proposed study will be one of the first studies in this area. Thus, it may also serve as a first step in a future line of research aimed at developing comprehensive pharmacological and psychosocial interventions in the treatment of anxiety in the elderly.

(b) HYPOTHESIS/RESEARCH QUESTIONS Study Hypothesis In a double-blind, placebo-controlled trial in elderly veterans diagnosed with GAD, sertraline will be more effective and equally safe as placebo in reducing symptoms of generalized anxiety disorder.

Research Question Will the presence of differences in PK (i.e., mean population values of steady state plasma concentrations) and plasma levels of sertraline explain differences in efficacy and side effect profile between and within the two fixed sertraline doses studied, if detected? (c) SPECIFIC OBJECTIVE The objective of the proposed study is to conduct a multi-site, double-blind, placebo-controlled trial evaluating the efficacy and safety of sertraline at fixed doses vs. placebo in the treatment of GAD among elderly primary care outpatient veterans.

Inclusion Criteria:

• Males and females of any race, ages 60 years and older.
• Willingness to accept randomization.
• Subjects who meet current DSM-IV criteria for a principal diagnosis of GAD
• Patients must have a minimum of a "moderately ill" rating on the Clinicians
• Global Impression-Severity Scale for GAD.
• Patients will have a score of 10 or more on the Hospital Anxiety and
• Depression Rating Scale-HADS-Anxiety subscale.
• Subjects entering the study will be free of psychotropic medications.

Exclusion Criteria:

• Subjects with DSM-IV current major depressive episode will be excluded.
• Subjects who exhibit suicidal ideation or are judged to be a significant
• suicide risk.
• Subjects who meet DSM-IV criteria for a substance (drug and alcohol) abuse and dependence disorder within the past 6 months
• Subjects who meet current or past DSM-IV criteria for psychotic disorder, or bipolar disorder.
• Subjects who meet DSM-IV criteria for dementia.
• Subjects with DSM-IV current major depressive episode will be excluded.
• Subjects who exhibit suicidal ideation or are judged to be a significant suicide risk.
• Subjects who meet DSM-IV criteria for a substance (drug and alcohol) abuse and dependence disorder within the past 6 months
• Subjects who meet current or past DSM-IV criteria for psychotic disorder, or bipolar disorder.
• Subjects who meet DSM-IV criteria for dementia.