Combined Treatment for Generalized Anxiety Disorder (GAD)

Phase 2

Completed

Conditions: Generalized Anxiety Disorder

Interventions: Behavioral: Cognitive Behavioral Therapy
Drug: Venlafaxine XR

Registration Number: NCT00620776

Lead Sponsor: University of Pennsylvania

Brief Summary: 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: The specific aims of this study are to collect preliminary data relevant to the following hypotheses:

1. Primary Hypothesis: Acute phase improvement for combined cognitive behavioral therapy (CBT) plus medication will be superior to medication alone.

2. 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.

3. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 69

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combined Treatment	Venlafaxine XR	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.
Venlafaxine XR 75-225 mg alone	Venlafaxine XR	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.
Combined Treatment	Cognitive Behavioral Therapy	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.

Primary Outcome Measures

Name	Time	Method
Hamilton Anxiety Rating Scale (HAM-A)	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.

Secondary Outcome Measures

Name	Time	Method
Hospital Anxiety Depression Scale (HAD)-Depression Score	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.
Clinical Global Impression (CGI)-Severity Score	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.
Clinical Global Impression (CGI)-Improvement Score	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.
Clinical Response Rate	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.
Hospital Anxiety Depression Scale (HAD)-Anxiety Score	Data collected as part of protocol 709012 at baseline, week 2, 4, 6, 8, 12, 16, 20, and 24	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.
Hamilton Rating Scale for Depression (HAM-D)-17-item Score	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.
Penn State Worry Questionnaire (PSWQ)	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.
Physical Component Score of the 12-Item Short Form Survey (SF-12)	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.
Quality of Life Subscale of the General Health Questionnaire (GHQ)	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.
Mental Component Score of the 12-item Short Form Survey (SF-12)	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.
50 Percent or Greater Reduction in PSWQ Score	Data collected as part of protocol 709012 at baseline, week 12, and week 24	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.