Combined Treatment for Generalized Anxiety Disorder (GAD)

• ClinicalTrials.gov Identifier: NCT00620776
• Recruitment Status: Completed
• First Posted: February 21, 2008
• Results First Posted: February 16, 2017
• Last Update Posted: February 16, 2017
• Sponsor: University of Pennsylvania
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Paul Crits-Christoph, University of Pennsylvania

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Generalized Anxiety Disorder	Behavioral: Cognitive Behavioral Therapy; Drug: Venlafaxine XR	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combined Treatment for Generalized Anxiety Disorder (GAD)
• Study Start Date: October 2006
• Actual Primary Completion Date: March 2008
• Actual Study Completion Date: March 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Combined Treatment; 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; 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.; Drug: Venlafaxine XR; 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).; Other Name: Effexor extended release
Active Comparator: Venlafaxine XR 75-225 mg alone; 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; 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).; Other Name: Effexor extended release

Outcome Measures

Primary Outcome Measures :

1. Hamilton Anxiety Rating Scale (HAM-A) [ Time Frame: 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 :

1. Hospital Anxiety Depression Scale (HAD)-Anxiety Score [ Time Frame: 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.
2. Hospital Anxiety Depression Scale (HAD)-Depression Score [ Time Frame: 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.
3. Hamilton Rating Scale for Depression (HAM-D)-17-item Score [ Time Frame: 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.
4. Clinical Global Impression (CGI)-Severity Score [ Time Frame: 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.
5. Clinical Global Impression (CGI)-Improvement Score [ Time Frame: 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.
6. Quality of Life Subscale of the General Health Questionnaire (GHQ) [ Time Frame: 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.
7. Penn State Worry Questionnaire (PSWQ) [ Time Frame: 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.
8. Physical Component Score of the 12-Item Short Form Survey (SF-12) [ Time Frame: 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.
9. Mental Component Score of the 12-item Short Form Survey (SF-12) [ Time Frame: 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.
10. Clinical Response Rate [ Time Frame: 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.
11. 50 Percent or Greater Reduction in PSWQ Score [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Pennsylvania

University of Pennsylvania, 3535 Market Street, Suite 650

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

University of Pennsylvania

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Paul Crits-Christoph, PhD; University of Pennsylvania

More Information

• Responsible Party: Paul Crits-Christoph, Professor of Psychology in Psychiatry, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00620776
• Other Study ID Numbers: 802307; 5R34MH072678-02 ( U.S. NIH Grant/Contract )
• First Posted: February 21, 2008
• Results First Posted: February 16, 2017
• Last Update Posted: February 16, 2017
• Last Verified: December 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Paul Crits-Christoph, University of Pennsylvania:

Generalized Anxiety Disorder; Cognitive Behavioral Therapy; Psychotherapy plus medication; Combined treatment

Additional relevant MeSH terms:

Disease; Anxiety Disorders; Pathologic Processes; Mental Disorders; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs