| ID | Type | Description | Link |
|---|---|---|---|
| R01MH039188-01 | U.S. NIH Grant/Contract | View source | |
| DSIR 84-CTS |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continued medication alone | Active Comparator | Participants will receive antidepressant treatment with fluoxetine for 30 weeks |
|
| Continued medication plus CBT | Experimental | Participants will receive antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluoxetine | Drug | Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Remission | Remission is defined as CDRS-R <=28. Timing of remission is based on clinical assessment using the CDRS-R and K-Life to identify the week at which point the patient remitted. | 30 weeks |
| Relapse | Relapse was defined as: 1) CDRS-R score >=40 with a history of 2 weeks of clinical deterioration or 2) CDRS-R<40, but with a 2 week history of significant clinical deterioration. | Measured at Weeks 12, 18, 24, and 30 |
| Remission | Remission is defined as CDRS-R <=28. | Measured at Weeks 12, 18, 24, and 30 |
| Measure | Description | Time Frame |
|---|---|---|
| K-Life (Time Well) | K-Life interview was conducted at Weeks 6, 12, 18, 24, and 30, with ratings for depressive illness for each week throughout the study. Ratings definitions: 1=Normal, no residual symptoms; 2=Presence of 1 or more symptosm in no more than mild degree; 3=Considerably less psychopathology than full criteria, but still obvious evidence of disorder with no more than moderate impairment; 4=Does not meet full criteria, but has major symptoms or impairment from the disorder; 5=Meets full criteria, but no extreme impairment; 6=Meets full criteria, and either has prominent psychotic symptoms or extreme impairment. Time well is defined as each week the depression rating was a 1 or 2. Percent time well was defined as each week the depression rating was a 1 or 2 divided by the total number of weeks in the study. Statistic: anova |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Graham J. Emslie, MD | University of Texas, Southwestern Medical Center at Dallas | Principal Investigator |
| Beth D. Kennard, PsyD | University of Texas, Southwestern Medical Center at Dallas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Medical Center of Dallas, Outpatient Psychiatry Clinic | Dallas | Texas | 75235 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24935082 | Result | 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. | |
| 40520979 | Derived | 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. |
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200 participants began acute phase open-label treatment with fluoxetine. Of these, 144 entered the randomized control study. Results data presented are for 144 participants randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Continued Medication Alone | n=69 Participants will receive antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks. |
| FG001 | Continued Medication Plus CBT | n=75 Participants will receive antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment Fluoxetine: Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks. 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Continued Medication Alone | Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks. |
| BG001 | Continued Medication Plus CBT |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Remission | Remission is defined as CDRS-R <=28. Timing of remission is based on clinical assessment using the CDRS-R and K-Life to identify the week at which point the patient remitted. | Posted | Mean | Standard Error | weeks | 30 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Continued Medication Alone | Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks. N=69 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for Suicide Attempt | Psychiatric disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Graham Emslie and Dr. Betsy Kennard | UT Southwestern Medical Center | 214-456-5900 | beth.kennard@utsouthwestern.edu |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
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| ID | Term |
|---|---|
| D005473 | Fluoxetine |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Relapse prevention cognitive behavioral therapy (CBT) | 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. |
|
|
| 30 weeks |
| Remission | Remission is defined as CDRS-R <=28 (up through week 30) or at least 8 consecutive weeks of a K-Life rating of 1 or 2. Timing of remission is based on clinical assessment using the CDRS-R and K-Life to identify the week at which point the patient remitted. | Weeks 52 and 78 |
| Relapse | Up through week 30, relapse was defined as: 1) CDRS-R score >=40 with a history of 2 weeks of clinical deterioration or 2) CDRS-R<40, but with a 2 week history of significant clinical deterioration. From week 31-78, relapse was assessed using the K-Life. Relapse was defined as at least 2 weeks of a K-Life rating of 5 or 6; participants may also be identified as relapsing with a K-Life rating of 4 if the rating was for several weeks and not strictly related to stressful life events. | Weeks 52 and 78 |
| 26598474 | Derived | 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. |
| 24360599 | Derived | 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. |
Participants received antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment
Fluoxetine: Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.
Relapse prevention cognitive behavioral therapy (CBT): After the first 6 weeks of treatment with fluoxetine, these participants were assigned to additionally receive relapse prevention CBT for the remaining 24 weeks of treatment. These participants attended 10 to 12 CBT sessions, during which they will learn specific skills to reduce and prevent the occurrence of residual depressive symptoms.
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline CDRS-R | Childhood Depression Rating Scale - Revised (CDRS-R) Total score range: 17-113 Scoring thresholds: >=40: moderate to severe depression; <=28: remission | Mean | Standard Deviation | units on a scale |
|
| Baseline CGI Severity | Clinical Global Impression - Severity Range: 1-7
| Mean | Standard Deviation | units on a scale |
|
|
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| Primary | Relapse | Relapse was defined as: 1) CDRS-R score >=40 with a history of 2 weeks of clinical deterioration or 2) CDRS-R<40, but with a 2 week history of significant clinical deterioration. | Only participants who achieved remission were analyzed for relapse rates, as only remitted patients can experience a relapse of depression. | Posted | Number | probability of relapse (%) | Measured at Weeks 12, 18, 24, and 30 |
|
|
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| Secondary | K-Life (Time Well) | K-Life interview was conducted at Weeks 6, 12, 18, 24, and 30, with ratings for depressive illness for each week throughout the study. Ratings definitions: 1=Normal, no residual symptoms; 2=Presence of 1 or more symptosm in no more than mild degree; 3=Considerably less psychopathology than full criteria, but still obvious evidence of disorder with no more than moderate impairment; 4=Does not meet full criteria, but has major symptoms or impairment from the disorder; 5=Meets full criteria, but no extreme impairment; 6=Meets full criteria, and either has prominent psychotic symptoms or extreme impairment. Time well is defined as each week the depression rating was a 1 or 2. Percent time well was defined as each week the depression rating was a 1 or 2 divided by the total number of weeks in the study. Statistic: anova | Posted | Mean | Standard Deviation | Weeks spent well | 30 weeks |
|
|
|
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| Secondary | Remission | Remission is defined as CDRS-R <=28 (up through week 30) or at least 8 consecutive weeks of a K-Life rating of 1 or 2. Timing of remission is based on clinical assessment using the CDRS-R and K-Life to identify the week at which point the patient remitted. | Posted | Number | Probability of remission (%) | Weeks 52 and 78 |
|
|
|
| Secondary | Relapse | Up through week 30, relapse was defined as: 1) CDRS-R score >=40 with a history of 2 weeks of clinical deterioration or 2) CDRS-R<40, but with a 2 week history of significant clinical deterioration. From week 31-78, relapse was assessed using the K-Life. Relapse was defined as at least 2 weeks of a K-Life rating of 5 or 6; participants may also be identified as relapsing with a K-Life rating of 4 if the rating was for several weeks and not strictly related to stressful life events. | Only participants who achieved remission were analyzed for relapse rates, as only remitted patients can experience a relapse of depression. | Posted | Number | Probability of Relapse (%) | Weeks 52 and 78 |
|
|
|
| Primary | Remission | Remission is defined as CDRS-R <=28. | Posted | Number | probability of remitting (%) | Measured at Weeks 12, 18, 24, and 30 |
|
|
|
| 7 |
| 69 |
| 0 |
| 69 |
| EG001 | Continued Medication Plus CBT | Participants received antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks. Relapse prevention cognitive behavioral therapy (CBT): After the first 6 weeks of treatment with fluoxetine, these participants were 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 learned specific skills to reduce and prevent the occurrence of residual depressive symptoms. N=75 | 9 | 75 | 0 | 75 |
| Hospitalization for Suicidal Ideation | Psychiatric disorders |
|
| Hospitalization for Agitation | Psychiatric disorders |
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| Hospitalization for medical conditions | General disorders |
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| Suicidal behavior that did not result in hospitalization | Psychiatric disorders |
|
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| D001523 |
| Mental Disorders |
| Week 24 |
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| Week 30 |
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| Week 24 |
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| Week 30 |
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