Official Title: “Pediatric MDD: Sequential Treatment With Fluoxetine and Relapse Prevention”

This study will compare the effectiveness of fluoxetine alone with the effectiveness of fluoxetine with cognitive behavioral therapy in increasing recovery and preventing relapse in youth with major depressive disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: January 2013

Major depressive disorder (MDD) is a serious psychiatric disorder that affects approximately 1 out of every 12 to 15 children and adolescents. Depression can cause problems with school, family, and friends, and if left untreated, these difficulties can persist into adulthood.

Treatments using antidepressants and forms of psychotherapy have been shown to be effective in reducing symptoms of depression. However, many youth experience a return of depressive symptoms within 1 to 2 years of remission. Recent studies have shown that adding cognitive behavioral therapy (CBT), a form of psychotherapy that focuses on behavioral modification, to initial antidepressant treatment may increase remission and reduce relapse rates. This study will compare the effectiveness of fluoxetine alone versus fluoxetine plus added CBT in increasing recovery and preventing relapse in youth with MDD.

Participation in this study will last 78 weeks. Potential participants will undergo initial screening, which will include interviews and questionnaires about mood, behavior, and medical history; vital sign measurements; blood draws; urine drug and pregnancy tests; a learning assessment; and a meeting with a psychiatrist. All eligible participants will then begin 6 weeks of treatment with fluoxetine. During this 6-week period, participants will attend weekly study visits, which will include vital sign measurements, questionnaires on symptoms and mood, and medication dosage adjustments. At Week 6, participants will be evaluated by an independent evaluator who will determine whether their depression has improved. Participants who have not improved with fluoxetine will end their study participation and will be provided with recommendations for other treatment options.

All participants who have shown improvement will continue to receive fluoxetine for another 24 weeks, for a total of 30 weeks of treatment. Half of these participants will be randomly assigned to additionally receive CBT for the remaining 24 weeks. All participants will attend study visits that will occur every other week for 3 months and then monthly for 3 months.

These visits will last 20 to 30 minutes and will include vital sign measurements and questions about mood and behavior. Participants receiving CBT will also attend 10 to 12 CBT sessions, which will last 50 minutes each and will occur weekly for the first 4 weeks, every other week for 1.5 months, and monthly for the last 3 months. The CBT sessions will involve both individual child and parent-child sessions, which will focus on modifying depressive thoughts, feelings, and behaviors. Participants will undergo repeat evaluations with the independent evaluator at Weeks 12, 18, 24, 30, 52, and 78.

Intervention(s) in this Clinical Trial

• Drug: Fluoxetine
  • Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.
• Behavioral: Relapse prevention cognitive behavioral therapy (CBT)
  • After the first 6 weeks of treatment with fluoxetine, some participants will be assigned to additionally receive relapse prevention CBT for the remaining 24 weeks of treatment. These participants will attend 10 to 12 CBT sessions, during which they will learn specific skills to reduce and prevent the occurrence of residual depressive symptoms.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Participants will receive antidepressant treatment with fluoxetine for 30 weeks
• Experimental: 2
  • Participants will receive antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment

Primary Measures

• Remission
  • Time Frame: Measured at Weeks 6, 12, 18, 24, 30, 52, and 78
    Safety Issue?: No
• Relapse
  • Time Frame: Measured at Weeks 6, 12, 18, 24, 30, 52, and 78
    Safety Issue?: No

Secondary Measures

• K-Life (percent time well and percent time ill)
  • Time Frame: Measured at Weeks 6, 12, 18, 24, 30, 52, and 78
    Safety Issue?: No

Inclusion Criteria:

• Primary diagnosis of nonpsychotic MDD (single or recurrent) for at least 4 weeks before study entry
• In good general medical health
• Normal intelligence

Exclusion Criteria:

• Lifetime history of any psychotic disorder, including psychotic depression
• Lifetime history of bipolar I and II disorders
• Alcohol or substance abuse or dependence within the 6 months before study entry
• Anorexia nervosa or bulimia within the 6 months before study entry
• Pregnant or breastfeeding females, or sexually active females not using medically acceptable means of birth control (e.g., IUD, birth control pills, barrier devices)
• Chronic medical illness (medically unstable and requires regular medication that may interfere with treatment interventions)
• Concurrent medication(s) with psychotropic effects (e.g., anticonvulsants, steroids, etc.) other than stable stimulant medication
• First degree relatives with bipolar I disorder
• Severe suicidal ideation or previous history of serious suicide attempt within this episode
• Prior failure to respond to an adequate treatment with fluoxetine (defined as at least 40 mg/day for 4 weeks)
• Non-English speaking

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 8 Years

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Graham J. Emslie, MD Principal Investigator University of Texas Southwestern Medical Center at Dallas  

Overall Contact: Jaime Murphy, BA 214-456-8918 jaime.murphy@utsouthwestern.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00612313

Study ID Number: 2-R01 MH039188-14A2

ClinicalTrials.gov Identifier: NCT00612313

Health Authority: United States: Federal Government