Clinical trial NCT00219349: Cognitive-Behavioral Therapy and Escitalopram for Generalized Anxiety Disorder(GAD)
Official title: Cognitive-Behavioral Therapy and Pharmacotherapy Augmentation for Generalized Anxiety Disorder: A Pilot Investigation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Generalized Anxiety Disorder
Keywords: Anxiety Disorders
Anxiety Neuroses
Behavior Therapy, Cognitive
Escitalopram
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2005-09-22
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goals of this pilot study are as follows:

1) To disseminate and examine the effectiveness of a manualized, individual, cognitive-behavioral psychotherapy (CBT) for adults with Generalized Anxiety Disorder(GAD), 2) to test the effectiveness of augmentation (the addition of) antidepressant therapy in participants who do not fully respond to CBT, and 3) to examine individual and clinical predictors of non-response to CBT and predictors of response to augmentation antidepressant therapy. A related goal is to examine the maintenance of treatment gains obtained from CBT alone and CBT with augmentation antidepressant therapy, over a twenty-four month follow-up period. This study will serve as a pilot investigation in preparation for a larger federally funded study using this treatment approach. We hypothesize that CBT will result in remission (no longer having GAD) and/or high endstate functioning (clinically meaningful improvement) in approximately 40-50% of participants. Further, we hypothesize that augmentation antidepressant therapy in participants who do not fully respond to CBT will result in further clinically significant improvement.

Detailed description: This pilot investigation will examine the effectiveness of augmenting cognitive behavioral therapy (CBT) with antidepressant pharmacotherapy (escitalopram\[Lexapro\]) in adults with generalized anxiety disorder (GAD) who do not fully respond to a temporally primary trial of CBT. A secondary aim of this study is to assess the maintenance of treatment gains made by patients in response to CBT, and to CBT with antidepressant augmentation therapy, over a two-year follow-up period.

CBT is an empirically supported psychotherapy that has been found to be effective in treating GAD in approximately 50 percent of patients enrolled in controlled clinical trials. However, a substantial proportion (nearly half) of individuals with GAD do not achieve full remission or clinically significant improvement at the cessation of CBT. Escitalopram (Lexapro)is a selective serotonin reuptake inhibitor (SSRI) antidepressant, which has been shown to be effective in treating GAD in several large-scale controlled clinical trials. The Food and Drug Administration has approved ecitalopram for the treatment of GAD.

The proposed research plan encompasses the conduct of an open clinical trial (No randomized placebo control) of 14 sessions of manualized individual CBT for persons meeting DSM-IV-TR diagnostic criteria for GAD. This study will use a treatment manual developed by Dr. Thomas Borkovec and colleagues at the Pennsylvania State University. Participants who meet high endstate functioning criteria and/or achieve remission following CBT will be evaluated periodically during a twenty-four month follow-up phase. Participants who do not meet high endstate functioning criteria and/or achieve remission following completion of CBT will be offered entry into a twelve-week, open-label, flexible-dose trial of escitalopram therapy. Participants receiving escitalopram therapy will be evaluated periodically during a twenty-four month follow-up phase, as well. It is anticipated that patients who do not fully respond to CBT will show a significant increment in improvement in GAD symptoms, over and above their CBT posttreatment level, following pharmacotherapy with escitalopram.

At present, no studies with GAD populations have examined the additive or sequenced effects of psychosocial therapy and SSRI antidepressant pharmacotherapy. The proposed research is a first step in this direction and may provide evidence supporting the use of combined treatment modalities in CBT partial and non-responders.

Eligibility criteria: Inclusion Criteria:

1. Males or females between the ages of 18 and 65 (inclusive)
2. Primary DSM-IV-TR diagnosis of Generalized Anxiety Disorder (GAD) with no significant co-morbid anxiety disorder for which CBT for GAD is not appropriate including PTSD, OCD, and prominent panic disorder with or without agoraphobia
3. A negative urine toxicology, i.e., a urine specimen that does not test positive for use of drugs of abuse, or use of benzodiazepines, in the previous three weeks
4. Penn State Worry Questionnaire score of 55 or greater
5. Have a score of equal to or \> 4 (Moderately Ill) on Clinical Global Impression (CGI) Scale (severity of illness item) for GAD
6. Ability to give informed consent
7. Fluent in English
8. Willingness to have Cognitive-Behavioral Therapy sessions audiotaped -

Exclusion Criteria:

1. Patients who have a diagnosis of Major Depressive Disorder within 60 days prior to the clinical interview, and patients who have a "lifetime" history of being diagnosed with one or more of the following disorders: Schizophrenia, Major Depressive Disorder with Psychotic or Catatonic features, Bipolar I Affective Disorder, or Organic Mental Disease
2. DSM-IV substance abuse or dependence within the past 6 months (except nicotine or caffeine)
3. Active suicidal or homicidal ideation, or judged to be at serious suicide risk
4. Hamilton Rating Scale for Depression score of greater than 20 at Screening or Baseline evaluation
5. Any unstable medical or neurological condition
6. Women who are pregnant or lactating
7. Having received CBT treatment for GAD previously
8. Concurrent psychosocial therapy
9. Current psychotropic medication with exception of zolpidem at hs for insomnia
10. History of nonresponse to an adequate trial of escitalopram or intolerable adverse effects to escitalopram -

Primary outcomes:
measure: Change in Hamilton Anxiety Rating Scale Score
timeFrame: week 14 to week 26
measure: Change in Clinical Global Impressions-Severity Index
timeFrame: week 14 to week 26
measure: Change in Generalized Anxiety Disorder Severity Scale
timeFrame: week 14 to week 26
measure: Change in Penn State Worry Questionnaire
timeFrame: week 14 to week 26
measure: Change in State-Trait Anxiety Inventory, State Subscale
timeFrame: week 14 to week 26
Secondary outcomes:
measure: Clinical Global Impressions-Improvement Index
timeFrame: week 26
measure: Change in Hamilton Rating Scale for Depression
timeFrame: week 14 to week 26
measure: Change in Beck Depression Inventory-II
timeFrame: week 14 to week 26
Other outcomes:
Locations:
city: New York
country: United States
facility: Anxiety Disorders Clinic, New York State Psychiatric Institute
state: New York
Study officials:
affiliation: New York State Psychiatric Institute
name: Franklin R. Schneier, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: New York State Psychiatric Institute
name: Kenneth D Belzer, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schneier FR, Belzer KD, Kishon R, Amsel L, Simpson HB. Escitalopram for persistent symptoms of generalized anxiety disorder after CBT: a pilot study. J Nerv Ment Dis. 2010 Jun;198(6):458-61. doi: 10.1097/NMD.0b013e3181da4d77.