Combined Treatment for Generalized Anxiety Disorder (GAD)

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.

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.

• 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).

• Experimental: Combined Treatment
  Patients who receive combined cognitive behavioral therapy (CBT) plus medication treatment for GAD
  Interventions:

  • Behavioral: Cognitive Behavioral Therapy
  • Drug: Venlafaxine XR
• Active Comparator: Medication alone
  These patients receive only medication treatment for GAD. Patients take venlafaxine as part of protocol 709012 and are assessed over a 6 month period.
  Intervention: Drug: Venlafaxine XR

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