Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse

NCT ID: NCT00612313

Last Updated: 2016-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2014-01-31

Brief Summary

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.

Detailed Description

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; a meeting with a psychiatrist; and lab draws and/or urine drug or pregnancy tests if indicated by the 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 significantly 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 significant 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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Continued medication alone

Participants will receive antidepressant treatment with fluoxetine for 30 weeks

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.

Continued medication plus CBT

Participants will receive antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment

Group Type: EXPERIMENTAL

Fluoxetine

Intervention Type: DRUG

Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.

Relapse prevention cognitive behavioral therapy (CBT)

Intervention Type: BEHAVIORAL

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.

Interventions

Fluoxetine

Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Prozac; CBT

Eligibility Criteria

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 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 ADHD 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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Graham Emslie

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Graham J. Emslie, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Beth D. Kennard, PsyD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Southwestern Medical Center at Dallas

Locations

Children's Medical Center of Dallas, Outpatient Psychiatry Clinic

Dallas, Texas, United States

Countries

United States

References

Kennard BD, Emslie GJ, Mayes TL, Nakonezny PA, Jones JM, Foxwell AA, King J. Sequential treatment with fluoxetine and relapse--prevention CBT to improve outcomes in pediatric depression. Am J Psychiatry. 2014 Oct;171(10):1083-90. doi: 10.1176/appi.ajp.2014.13111460.

Reference Type: RESULT

PMID: 24935082 (View on PubMed)

Croarkin PE, Nakonezny PA, Morris DW, Rush AJ, Kennard BD, Emslie GJ. Performance and Psychometric Properties of Novel Brief Assessments for Depression in Children and Adolescents. JAACAP Open. 2024 May 27;3(2):335-343. doi: 10.1016/j.jaacop.2024.05.002. eCollection 2025 Jun.

Reference Type: DERIVED

PMID: 40520979 (View on PubMed)

Emslie GJ, Kennard BD, Mayes TL, Nakonezny PA, Moore J, Jones JM, Foxwell AA, King J. Continued Effectiveness of Relapse Prevention Cognitive-Behavioral Therapy Following Fluoxetine Treatment in Youth With Major Depressive Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):991-8. doi: 10.1016/j.jaac.2015.09.014. Epub 2015 Oct 8.

Reference Type: DERIVED

PMID: 26598474 (View on PubMed)

Croarkin PE, Nakonezny PA, Husain MM, Port JD, Melton T, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. Brain Stimul. 2014 Mar-Apr;7(2):243-51. doi: 10.1016/j.brs.2013.11.006. Epub 2013 Dec 3.

Reference Type: DERIVED

PMID: 24360599 (View on PubMed)

Other Identifiers

R01MH039188-01

Identifier Type: NIH

Identifier Source: secondary_id

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DSIR 84-CTS

Identifier Type: -

Identifier Source: secondary_id

R01MH039188-01

Identifier Type: NIH

Identifier Source: org_study_id

View Link

NCT00599300

Identifier Type: -

Identifier Source: nct_alias