Clinical trial NCT00612313: Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse
Official title: Pediatric MDD: Sequential Treatment With Fluoxetine and Relapse Prevention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Keywords: Major Depressive Disorder
MDD
Children
Adolescents
Antidepressant
CBT
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2008-02-11
Enrollment: 144
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Remission
timeFrame: 30 weeks
measure: Relapse
timeFrame: Measured at Weeks 12, 18, 24, and 30
measure: Remission
timeFrame: Measured at Weeks 12, 18, 24, and 30
Secondary outcomes:
measure: K-Life (Time Well)
timeFrame: 30 weeks
measure: Remission
timeFrame: Weeks 52 and 78
measure: Relapse
timeFrame: Weeks 52 and 78
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Children's Medical Center of Dallas, Outpatient Psychiatry Clinic
state: Texas
Study officials:
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Graham J. Emslie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas, Southwestern Medical Center at Dallas
name: Beth D. Kennard, PsyD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.