Cognitive-Behavioral Therapy and Escitalopram for Generalized Anxiety Disorder(GAD)

Cognitive-Behavioral Therapy and Pharmacotherapy Augmentation for Generalized Anxiety Disorder: A Pilot Investigation

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00219349

Enrollment

Registered

2005-09-22

Start date

2005-01-31

Completion date

2008-07-31

Last updated

2017-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Generalized Anxiety Disorder

Keywords

Anxiety Disorders, Anxiety Neuroses, Behavior Therapy, Cognitive, Escitalopram

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.

Interventions

BEHAVIORALCognitive Behavioral Therapy

14 weekly sessions of individualized CBT

DRUGescitalopram

10-20 mg per day for 12 weeks

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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 -

Design outcomes

Primary

Measure	Time frame	Description
Change in Hamilton Anxiety Rating Scale Score	week 14 to week 26	The Hamilton Anxiety Rating Scale is a clinician administered rating scale assessing severity of anxiety from 0 (low) to 64 (high). The greater the magnitude of decrease in score during treatment, the greater the improvement in anxiety.
Change in Clinical Global Impressions-Severity Index	week 14 to week 26	7 point scale of overall severity of psychopathology from 1 mildest to 7 most severe.
Change in Generalized Anxiety Disorder Severity Scale	week 14 to week 26	measures severity of symptoms of generalized anxiety disorder, reported as a total score summing 10 items that are each rated from 0, never to 4, all of the time. Range is 0 to 40, with 40 most severe.
Change in Penn State Worry Questionnaire	week 14 to week 26	total score (of 16 items) ranging from 16 (least worry) to 80 (most worry)
Change in State-Trait Anxiety Inventory, State Subscale	week 14 to week 26	only the total score of the state anxiey subscale was used. Range is from 20 (mildest) to 80 (most severe)

Secondary

Measure	Time frame	Description
Clinical Global Impressions-Improvement Index	week 26	This is a single item rating overall symptomatic improvement. Range is 0 (very much worse) to 7 (very much improved)
Change in Hamilton Rating Scale for Depression	week 14 to week 26	24 item version of this standard depression scale, total score ranges from 0 (not depressed) to 58 (most severe)
Change in Beck Depression Inventory-II	week 14 to week 26	total score ranges from 0 (not depressed) to 63 (most severe)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Cognitive-behavioral Therapy 14 weekly sessions of individual cognitive-behavioral therapy	25
Total	25

Withdrawals & dropouts

Period	Reason	FG000
Cognitive Behavioral Therapy Phase	Lost to Follow-up	6
Cognitive Behavioral Therapy Phase	Protocol Violation	2
Cognitive Behavioral Therapy Phase	Withdrawal by Subject	2
Escitalopram Phase	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Cognitive-behavioral Therapy
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	25 Participants
Age, Continuous	41 years STANDARD_DEVIATION 11.8
Region of Enrollment United States	25 participants
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	14 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	2 / 25
serious Total, serious adverse events	0 / 25