Generalized Anxiety Disorder
Conditions
Keywords
sertraline, pharmacotherapy, geriatric
Brief summary
Generalized anxiety disorder (GAD) is a very common disorder in the geriatric population with prevalence rates reaching 7% and even higher rates of 8% among elderly veterans. However, despite such high prevalence treating clinicians are presently forced to address treatment issues in this population without the guidance of scientific data. This proposal aims to begin to address this void. In light of emerging information regarding efficacy of the newer anti anxiety agents, specifically the selective serotonin reuptake inhibitors (SSRIs), in the treatment of young adult GAD patients it is time to prospectively evaluate the safety and efficacy of these medications in the treatment of elderly GAD patients. Therefore, this study will examine the effects and safety of the SSRI sertraline at different doses (50mg and 100mg per day) for older patients with GAD.
Detailed description
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 pharmacokinetics (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.
Interventions
50 mg daily
DRUGsertraline 100 mg daily
100 mg daily
DRUGPlacebo 50 or 100 mg
50mg or 100mg matching placebo
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females of any race, ages 60 years and older. * Willingness to accept randomization. * Subjects who meet current (Diagnostic and Statistical Manual of Psychiatric Disorders forth edition (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparisons of End of Study HAM-A Score Means for Sertraline 50 mg vs Placebo, Sertraline 100 mg vs Placebo, and Sertraline 50 mg vs. Sertraline 100 mg | 11 weeks from baseline | Least squares (LS) means estimate and p-value from mixed effects model with baseline and site as covariates and Tukey-Kramer adjustment for multiple comparisons Hamilton Rating Scale for Anxiety (HAM-A) is a widely used rating scale for anxiety describes the presence/absence of the severity of anxiety symptoms. It's clinician-rated scale of 14 items rated from 0-4. Generally, total score of \<17 is mild anxiety; 18-24 is mild to moderate, and 25 and up is moderate to severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sertraline 50mg sertraline 50mg per day
sertraline 50 mg daily: 50 mg daily | 14 |
| Sertraline 100mg sertraline 100mg per day
sertraline 100 mg daily: 100 mg daily | 14 |
| Placebo matching placebo
Placebo 50 or 100 mg: matching placebo | 14 |
| Total | 42 |
Baseline characteristics
| Characteristic | Sertraline 50mg | Sertraline 100mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 9 Participants | 9 Participants | 26 Participants |
| Gender Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Gender Male | 13 Participants | 14 Participants | 14 Participants | 41 Participants |
| Region of Enrollment United States | 14 participants | 14 participants | 14 participants | 42 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 14 | 4 / 14 | 3 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
Comparisons of End of Study HAM-A Score Means for Sertraline 50 mg vs Placebo, Sertraline 100 mg vs Placebo, and Sertraline 50 mg vs. Sertraline 100 mg
Least squares (LS) means estimate and p-value from mixed effects model with baseline and site as covariates and Tukey-Kramer adjustment for multiple comparisons Hamilton Rating Scale for Anxiety (HAM-A) is a widely used rating scale for anxiety describes the presence/absence of the severity of anxiety symptoms. It's clinician-rated scale of 14 items rated from 0-4. Generally, total score of \<17 is mild anxiety; 18-24 is mild to moderate, and 25 and up is moderate to severe.
Time frame: 11 weeks from baseline
Population: sertraline 50mg group and placebo group each had 2 subjects with missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sertraline 50mg | Comparisons of End of Study HAM-A Score Means for Sertraline 50 mg vs Placebo, Sertraline 100 mg vs Placebo, and Sertraline 50 mg vs. Sertraline 100 mg | 10.638 units on a scale |
| Sertraline 100mg | Comparisons of End of Study HAM-A Score Means for Sertraline 50 mg vs Placebo, Sertraline 100 mg vs Placebo, and Sertraline 50 mg vs. Sertraline 100 mg | 10.008 units on a scale |
| Placebo | Comparisons of End of Study HAM-A Score Means for Sertraline 50 mg vs Placebo, Sertraline 100 mg vs Placebo, and Sertraline 50 mg vs. Sertraline 100 mg | 9.357 units on a scale |