Official Title: “Imaging Antidepressant vs. Cognitive Behavior Therapy Effects on Unipolar Depression”

Our goals are 1) to use functional magnetic resonance imaging (fMRI) to predict which depressed individuals will respond to different validated treatments for unipolar depression including Cognitive Therapy (CT) and antidepressant medications (selective serotonin reuptake inhibitors; SSRIs) and 2) to understand whether CT and SSRIs affect similar aspects of brain function underlying cognition and emotion. Thus, we will examine depressed adults ages 18-55 using fMRI during cognitive and emotional information processing tasks, before and after treatment with an SSRI (n=25) or CT (n=40). We hypothesize that: 1) Recovery will occur in treatment with an SSRI primarily for individuals with increased reactivity in limbic brain regions associated with emotion generation and prefrontal regions associated with regulation,. 2) Recovery with CT will occur for patients with increased activity in brain regions associated with emotion generation but decreased activity in prefrontal regions associated with emotion regulation. 3) Recovery with an SSRI will yield similar changes in brain function to CT in brain regions associated with emotion generation but less change in brain regions responsible for emotion regulation such as the prefrontal cortex. Findings from this study may have a profound impact on reducing the burden of clinical depression by providing evidenced-based diagnostic and treatment guidelines.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment

Study Primary Completion Date: May 2010

Same as above.

Intervention(s) in this Clinical Trial

• Drug: SSRI
  • SSRI: 25 patients will receive 14 weeks of an FDA approved selective serotonin reuptake inhibitor (SSRI), administered under the supervision of a staff psychiatrist. After an initial 30-45 minute session patients will be seen for 15-30 minute sessions for 16-20 sessions over 14 weeks. Medication will begin with 10mg escitalopram daily (or its equivalent), increased to 30 mg/day (or its equivalent) by week 6 if pt has not achieved a minimum level of response (i.e., CGI < 2) and tolerability is adequate. Nonresponse at week 10 (CGI < 2) will be cause for medication switch or augmentation.
• Behavioral: CBT
  • Cognitive Behavior Therapy: 40 patients will receive 16- 20 60 minute sessions of procedurally determined Cognitive Therapy (Beck, 1979) over 14 weeks. Patients will begin with 2 sessions per week which may be reduced to once per week in the latter part of the study period if the patient is responding to the therapy. Cognitive Therapy is designed to teach skills that help to reduce depressive severity. Each session will be videotaped and will include homework to be completed and brought to the following session.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: SSRIs
  • Selective Serotonin Reuptake Inhibitors
• Active Comparator: CBT
  • Cognitive Behavior Therapy

Primary Measures

• Treatment outcome will be assessed on a variety of dimensions including change in symptoms, self-reported rumination, behavioral performance on cognitive tasks, and physiological reactivity to emotional information processing tasks.
  • Time Frame: 14-16 weeks
    Safety Issue?: No

Inclusion Criteria:

• 1. Meet DSM-IV criteria for major depressive disorder (one or more lifetime episodes, separated by at least two months of a return to normal functioning, in a current episode).
• 2. Male or female outpatients between the ages of 18 and 55 at time of enrollment.
• 3. Females only must be surgically sterile, post-menopausal for at least one year, or not pregnant and using a method of birth control that is acceptable to the investigator.
• 4. Have a total score of 14 or more on the first 17-items of the HRSD at both the initial and secondary interviews.
• 5. Be in reasonably good health. Patients with hypothyroidism, diabetes, high blood pressure, chronic respiratory, or other medical conditions may be considered candidates for study enrollment at the discretion of the investigator if their conditions are stable, they have been receiving standard therapies for the treatment of the condition, the prescribed dose and regiment of medication has been stable for at least 3 months, and all appropriate clinical and lab parameters are within normal limits for the condition that are clinically acceptable to the investigator
• 6. Be free of prescription psychotropic medications for two weeks (four weeks for fluoxetine) before study entry.
• 7. Provide written informed consent

Exclusion Criteria:

• 1. Being unable to complete questionnaires written in English, representing an active suicide risk (see below), active alcohol or drug dependence, having any eye problems or difficulties in corrected vision, having a North American Adult Reading Test (NAART) equivalent FSIQ < 85.
• 2. Pregnant women and those planning to become pregnant during the first 11 months after intake will also be excluded from the study. Pregnancy will be determined by self-report at the interview and by a pregnancy test at the time of the MRI scan.
• There will be no cost to the participant for the pregnancy test.
• 3. People who have metallic foreign objects in their body, such as aneurysm clips or pacemakers, as well as individuals prone to panicking in enclosed spaces will be excluded from the study. Subjects with a questionable history of metallic fragments will also be excluded.
• 4. Participants who are taking psychotropic medications, particularly antidepressant medications within two weeks of study entry (4 weeks for fluoxetine) will be excluded.
• 5. Participants will not be excluded on the basis of herbs, supplements, and other prescription or over the counter drugs other than those noted. HIV serostatus will not be evaluated for the research study.
• 6. At the initial screening visit, if girth seems to present a potential issue for the MRI, than width of participant will be assessed using a hula-hoop that is approximately the same diameter as the MR scanner. If subject exceeds the width of the hula-hoop, then they will be excluded from the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Pittsburgh

Overall Clinical Trial Officials and Contacts

Greg J Siegle, PhD Principal Investigator University of Pittsburgh  

Overall Contact: Susan R Berman 412-246-6111 bermansr@upmc.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00787501

Study ID Number: PRO07100326

ClinicalTrials.gov Identifier: NCT00787501

Health Authority: United States: Institutional Review Board

Dr. Siegle's PICAN lab website

MDTRP website