Generalized Anxiety Disorder
Conditions
Brief summary
This study will assess whether adding cognitive behavioral therapy to the antidepressant escitalopram is effective in reducing anxiety in older adults with generalized anxiety disorder.
Detailed description
Generalized anxiety disorder (GAD) affects nearly 6.8 million adults in the United States. GAD is diagnosed when a person spends at least 6 months excessively worrying over everyday problems to the point that carrying out normal life becomes difficult. People with GAD face each day with intense anxiety and tension and are unable to alleviate their worries. Physical symptoms of GAD include muscle aches, nausea, sweating, exhaustion, irritability, frequent urination, shaking, and hot flashes. People with GAD often experience other anxiety disorders, depression, or substance abuse, all of which can worsen symptoms of GAD. This makes early and appropriate treatment for GAD important. Current treatments for GAD include medication and/or types of psychotherapy. This study will assess whether adding cognitive behavioral therapy (CBT) to the antidepressant escitalopram is effective in reducing anxiety in older adults with GAD. Participation in this double-blind study will last up to 13 months. Participants will be asked to stop any current treatments for anxiety or depression for the duration of the study. Participants will begin taking one pill of the medication escitalopram daily for 12 weeks. Dosage will be increased to two pills each day if symptoms do not improve within 4 weeks. After 12 weeks, all participants will continue taking escitalopram for an additional 16 weeks. In addition, some participants will be randomly assigned to receive 16 weekly sessions of CBT, lasting 1 hour each. CBT sessions will involve learning relaxation techniques and other skills to manage anxiety and completing 30-minute at-home practice assignments each day. A family member will accompany participants to the first four CBT sessions. All participants will be asked to provide information for a close contact, who will be interviewed at baseline, Month 3, and Month 7 about how the participant's anxiety is affecting his or her relationships. After the 16-week period, participants will again be randomly assigned to receive either continued escitalopram or a placebo for an additional 28 weeks. Participants assigned to the placebo will be gradually tapered off escitalopram over a 6-week period. Participants who were receiving CBT will receive three more sessions. Throughout the study, participants will be asked to complete various assessments, including questionnaires, memory and thinking tests, and attention evaluations. Blood samples will be taken at Weeks 2 and 8, and saliva samples will be taken at baseline and Weeks 12, 28, and 56.
Interventions
DRUGEscitalopram
20 mg daily oral escitalopram
DRUGPlacebo
Placebo pill of daily oral escitalopram
BEHAVIORALCognitive behavioral therapy (CBT)
16 weekly 1-hour sessions
Sponsors
National Institute of Mental Health (NIMH)
Veterans Medical Research Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Principal (i.e., most severe or pressing problem) or co-principal current diagnosis of generalized anxiety disorder * Pretreatment score of at least 17 on Hamilton Anxiety Rating Scale
Exclusion criteria
* Principal diagnosis other than GAD * Clinically judged too psychiatrically unstable to participate in the study * Cognitive impairment or dementia * Alcohol or other substance use disorder within 6 months prior to study entry * Lifetime diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or bipolar disorder * Serious, unstable, or terminal medical condition that would compromise study participation or preclude the use of escitalopram, as determined by a review of medical records * Use of psychotropics that could not be safely tapered and discontinued for at least 2 weeks prior to study entry * Use of depot neuroleptics within 6 weeks prior to study entry * Unwillingness to terminate other forms of psychotherapy * Already received adequate trial of escitalopram or CBT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Anxiety Rating Scale | 56 weeks | The Hamilton Anxiety Rating Scale is a clinician-rated measure of cognitive and somatic anxiety symptoms. It consists of 14 items, each of which is scored on a 0-4 scale, summed for a total score ranging from 0 to 56. Inclusion criteria for this study included a Hamilton score \>= 17. The Hamilton, administered by blind raters, will be used to test hypotheses number 1 and 2. The outcome of interest is the number of participants who relapse, defined as having a Hamilton increase of \>=5, for a total Hamilton \>=14, relative to the end of the continuation phase (week 28), for a duration of at least 2 weeks, plus both clinician's and participant's judgment that the participant is experiencing a recurrence of anxiety symptoms. HAMA scores range from 0 (no anxiety) to 56 (high anxiety). |
| Penn State Worry Questionnaire | 56 weeks | The Penn State Worry Questionnaire is a 16-item measure of pathological worry. Scores range from 16-80, with higher scores indicating higher levels of worry. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram + CBT 12 weeks open-label escitalopram, 16 weeks cognitive behavioral therapy plus continuation escitalopram, 28 weeks maintenance escitalopram
Escitalopram: 20 mg daily oral escitalopram
Cognitive behavioral therapy (CBT): 16 weekly 1-hour sessions | 18 |
| Escitalopram + no CBT 12 weeks open-label escitalopram, 16 weeks continuation escitalopram, 28 weeks maintenance escitalopram
Escitalopram: 20 mg daily oral escitalopram | 18 |
| Placebo + CBT 12 weeks open-label escitalopram, 16 weeks cognitive behavioral therapy plus continuation escitalopram, 28 weeks pill placebo
Escitalopram: 20 mg daily oral escitalopram
Placebo: Placebo pill of daily oral escitalopram
Cognitive behavioral therapy (CBT): 16 weekly 1-hour sessions | 19 |
| Placebo + no CBT 12 weeks open-label escitalopram, 16 weeks continuation escitalopram, 28 weeks pill placebo
Escitalopram: 20 mg daily oral escitalopram
Placebo: Placebo pill of daily oral escitalopram | 18 |
| Total | 73 |
Baseline characteristics
| Characteristic | Total | Escitalopram + CBT | Escitalopram + no CBT | Placebo + CBT | Placebo + no CBT |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 46 Participants | 12 Participants | 11 Participants | 11 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 6 Participants | 7 Participants | 8 Participants | 6 Participants |
| Age, Continuous | 69.5 years STANDARD_DEVIATION 7.5 | 70.5 years STANDARD_DEVIATION 7.7 | 70.3 years STANDARD_DEVIATION 8.6 | 70.2 years STANDARD_DEVIATION 8.1 | 66.9 years STANDARD_DEVIATION 5.7 |
| Race/Ethnicity, Customized African American | 10 participants | 4 participants | 4 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Caucasian | 57 participants | 13 participants | 13 participants | 16 participants | 15 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants | 1 participants | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 73 participants | 18 participants | 18 participants | 19 participants | 18 participants |
| Sex: Female, Male Female | 52 Participants | 12 Participants | 14 Participants | 13 Participants | 13 Participants |
| Sex: Female, Male Male | 21 Participants | 6 Participants | 4 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 19 | 0 / 18 |
Outcome results
Primary
Hamilton Anxiety Rating Scale
The Hamilton Anxiety Rating Scale is a clinician-rated measure of cognitive and somatic anxiety symptoms. It consists of 14 items, each of which is scored on a 0-4 scale, summed for a total score ranging from 0 to 56. Inclusion criteria for this study included a Hamilton score \>= 17. The Hamilton, administered by blind raters, will be used to test hypotheses number 1 and 2. The outcome of interest is the number of participants who relapse, defined as having a Hamilton increase of \>=5, for a total Hamilton \>=14, relative to the end of the continuation phase (week 28), for a duration of at least 2 weeks, plus both clinician's and participant's judgment that the participant is experiencing a recurrence of anxiety symptoms. HAMA scores range from 0 (no anxiety) to 56 (high anxiety).
Time frame: 56 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram + CBT | Hamilton Anxiety Rating Scale | 18 participants |
| Escitalopram + no CBT | Hamilton Anxiety Rating Scale | 15 participants |
| Placebo + CBT | Hamilton Anxiety Rating Scale | 14 participants |
| Placebo + no CBT | Hamilton Anxiety Rating Scale | 8 participants |
p-value: <0.001Log Rank
Primary
Penn State Worry Questionnaire
The Penn State Worry Questionnaire is a 16-item measure of pathological worry. Scores range from 16-80, with higher scores indicating higher levels of worry.
Time frame: 56 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram + CBT | Penn State Worry Questionnaire | 52.8 units on a scale | Standard Deviation 2.6 |
| Escitalopram + no CBT | Penn State Worry Questionnaire | 53.4 units on a scale | Standard Deviation 10.3 |
| Placebo + CBT | Penn State Worry Questionnaire | 54.4 units on a scale | Standard Deviation 11.7 |
| Placebo + no CBT | Penn State Worry Questionnaire | 57.7 units on a scale | Standard Deviation 12.7 |
p-value: 0.01Mixed Models Analysis