Combined Treatment for Generalized Anxiety Disorder (GAD)

Study Overview
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Brief Summary
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The purpose of this study is to conduct a preliminary evaluation of the efficacy of combined medication and psychotherapy for generalized anxiety disorder (GAD). The general goals of the current study are to conduct a late stage treatment development study. The goal of this stage of research is to provide a preliminary answer to the question and to gather data to estimate intervention parameters (e.g., effect size, attrition rates, response rates) that would assist in planning further research.

Detailed Description
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The specific aims of this study are to collect preliminary data relevant to the following hypotheses: Primary Hypothesis: Acute phase improvement for combined cognitive behavioral therapy (CBT) plus medication will be superior to medication alone. Secondary Hypotheses: Combined CBT plus medication will be superior to medication alone on a number of secondary outcome measures, including the core feature of GAD (worry), depressive symptoms, functional impairment, and quality of life. Additional Exploratory Aim: We will explore the comparative relapse rates for the combined CBT plus medication treatment and the medication alone treatment condition at 6-month follow-up.

Official Title
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Combined Treatment for Generalized Anxiety Disorder (GAD)

Conditions
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Generalized Anxiety Disorder

Intervention / Treatment
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* Behavioral: Cognitive Behavioral Therapy
* Drug: Venlafaxine XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GAD diagnosis by structured interview Hamilton Anxiety Scale score of 18 or less Clinical Global Impressions Scale score of at least 4 Hamilton Depression Scale score of 18 or less Hamilton Depression Scale suicide item score less than 2 Use of an effective form of contraception throughout the s Exclusion Criteria: Hypersensitivity to venlafaxine XR History of seizures Episode of major depressive disorder in the previous 6 months History of any psychotic illness, bipolar disorder, or dementia Substance abuse and dependence during the past 6 months Other anxiety disorders with the exception of social phobia as long as GAD is primary Regular use of anxiolytics or antidepressants within 7 days of study onset Use of fluoxetine or monoamine oxidase inhibitors within 28 days of study onset (low dose usage of benzodiazepines will not prevent participation) Use of other psychotic medication besides benzodiazepines

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Treatment<br>Patients who receive combined cognitive behavioral therapy (CBT) plus medication (venlafaxine XR, flexibly dosed between 75-225 mg/day) treatment for GAD. CBT was once/week sessions for 12 weeks. Medication continued for the full 6 months. | Behavioral: Cognitive Behavioral Therapy<br>* This cognitive behavioral therapy for GAD has a cognitive restructuring component and an applied relaxation component. Patients will be educated about the nature of anxiety and be trained in the recognition and monitoring of situational, physiological, cognitive, and behavioral cues associated with anxious responding. They will be guided through copings skill rehearsals in addition to imaginal and in vivo exposure to anxiety cues. This cognitive behavioral treatment will consist of 1 to 1.5 hour sessions of psychotherapy, which will be held once weekly over a period of 12 weeks.<br>Drug: Venlafaxine XR<br>* Venlafaxine XR, 75-225 mg/d, oral administration. 14 days at 75 mg/d, 150 mg/d for the remaining 6 months, 225 mg/3 for patients unimproved at week 6, tapered at 75 mg/week (this intervention is provided by protocol 709012).<br>* Other names: Effexor extended release;|
| Active Comparator: Venlafaxine XR 75-225 mg alone<br>These patients receive only medication treatment for GAD. Patients take venlafaxine (flexibly dosed from 75-225 mg/day) as part of NCT00183274 and are assessed over a 6 month period. Medication continued for the full 6 months. | Drug: Venlafaxine XR<br>* Venlafaxine XR, 75-225 mg/d, oral administration. 14 days at 75 mg/d, 150 mg/d for the remaining 6 months, 225 mg/3 for patients unimproved at week 6, tapered at 75 mg/week (this intervention is provided by protocol 709012).<br>* Other names: Effexor extended release;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Anxiety Rating Scale (HAM-A) | The HAM-A was used to measure the severity of anxiety symptoms. The scale consists of 14 items; each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate and 25-30 moderate to severe anxiety. This measure was conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Anxiety Depression Scale (HAD)-Anxiety Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater anxiety. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 
| Hospital Anxiety Depression Scale (HAD)-Depression Score | The HAD was used to assess patients' report of anxiety and depressive symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. A higher score indicates greater depression. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 
| Hamilton Rating Scale for Depression (HAM-D)-17-item Score | The 17-item version of the HAM-D was used to assess severity of depressive symptoms. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.The total score is the sum of the 17 items, with a range from 0 to 50. A higher scores indicates greater depression. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. The evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 
| Clinical Global Impression (CGI)-Severity Score | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (1=normal; 7 = extremely ill) that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 
| Clinical Global Impression (CGI)-Improvement Score | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale (1= very much improved; 7 = very much worse) that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The ratings were conducted by research psychiatrists trained and highly experienced in the use of these scales. Evaluators were blind to group assignment. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 
| Quality of Life Subscale of the General Health Questionnaire (GHQ) | The General Health Questionnaire (GHQ) is a psychometric screening tool to identify common psychiatric conditions. Patients completed the 12 quality of life questions (each on a 0 to 3 scale) on this questionnaire. Scores on the 12 items were added up to create summary score (range = 0 to 36). Higher scores indicate worse health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 
| Penn State Worry Questionnaire (PSWQ) | The Penn State Worry Questionaire is a 16-item inventory that aims to measure the trait of worry, using Likert rating from 1 (not at all typical of me) to 5 (very typical of me). A total score is calculated (range = 16 to 80), with higher scores indicating greater worry. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 
| Physical Component Score of the 12-Item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 
| Mental Component Score of the 12-item Short Form Survey (SF-12) | The Short Form (12) Health Survey is a 12-item, patient-reported survey of patient health. Physical and Mental Health Component Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 
| Clinical Response Rate | Clinical response on the HAM-A was defined as a 50% or greater reduction from baseline to last value with the 24-week open label medication phase. | Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24 | 
| 50 Percent or Greater Reduction in PSWQ Score | Clinically significant change was defined on the PSWQ as an estimated (based on linear mixed effects model) endpoint score of less than 50.9. This score was calculated using the PSWQ normative data provided by Gillis, Haaga, and Ford (1995) and the baseline PSWQ mean and standard deviation (SD) from the current sample. The PSWQ mean and SD from the normative and current GAD samples were entered into the Jacobson et al. (1984) formula c for clinically significant change. This method provides a cutoff indicating whether or not the level of functioning by a patient is statistically more likely to be in the functional rather than the dysfunctional population. | Data collected as part of protocol 709012 at baseline, week 12, and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined treatment, Generalized Anxiety Disorder, Cognitive Behavioral Therapy, Psychotherapy plus medication