DepressionNCT00612313
Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse
A study testing Fluoxetine and Relapse prevention cognitive behavioral therapy (CBT) in people with Depression, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Depression
- What is being tested?
- Fluoxetine and Relapse prevention cognitive behavioral therapy (CBT)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Jan 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Primary diagnosis of nonpsychotic MDD (single or recurrent) for at least 4 weeks before study entry
- In good general medical health
- Normal intelligence
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Medical Center of Dallas, Outpatient Psychiatry Clinic
Dallas, Texas, 75235
About this study
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.
Read the 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
- Being tested
- Fluoxetine, Relapse prevention cognitive behavioral therapy (CBT)
- Keywords
- Major Depressive Disorder, MDD, Children, Adolescents, Antidepressant, CBT
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluoxetineDrug
Also called Prozac
Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.
Relapse prevention cognitive behavioral therapy (CBT)Behavioural
Also called 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.
| Study group | Role | What they receive |
|---|---|---|
| Continued medication alone | Active comparator | Participants will receive antidepressant treatment with fluoxetine for 30 weeks Receives: Drug: Fluoxetine |
| 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 Receives: Drug: Fluoxetine; Behavioral: Relapse prevention cognitive behavioral therapy (CBT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 weeks
Relapse
Relapse was defined as:
- 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: Measured at Weeks 12, 18, 24, and 30
Remission
Remission is defined as CDRS-R <=28.
Measured: Measured at Weeks 12, 18, 24, and 30
Secondary outcomes (3)
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
Measured: 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.
Measured: Weeks 52 and 78
Relapse
Up through week 30, relapse was defined as:
- 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.
Measured: Weeks 52 and 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionFeb 2013
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of Texas Southwestern Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Graham Emslie, University of Texas Southwestern Medical Center
- Investigators
- Graham J. Emslie, MD, Principal investigator, University of Texas, Southwestern Medical Center at DallasBeth D. Kennard, PsyD, Principal investigator, University of Texas, Southwestern Medical Center at Dallas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612313
- Sponsor's protocol ID
- R01MH039188-01
- Other IDs
- R01MH039188-01, DSIR 84-CTS
- Status last verified
- Dec 2015
- First submitted
- 7 Feb 2008
- Last updated
- 7 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24935082Croarkin 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.
PubMed 40520979Emslie 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.
PubMed 26598474Croarkin 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.
PubMed 24360599
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric MDD: Sequential Treatment With Fluoxetine and Relapse Prevention
- ClinicalTrials.gov ID
- NCT00612313
- Acronym / sponsor ID
- R01MH039188-01
- Conditions
- Depression
- Keywords
- Major Depressive Disorder, MDD, Children, Adolescents, Antidepressant, CBT
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2008
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 17 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continued medication alone | Active comparator | Drug: FluoxetineParticipants will receive antidepressant treatment with fluoxetine for 30 weeks |
| Continued medication plus CBT | Experimental | Drug: Fluoxetine, Behavioral: Relapse prevention cognitive behavioral therapy (CBT)Participants will receive antidepressant treatment with fluoxetine for 30 weeks plus relapse prevention cognitive behavioral therapy for the last 24 weeks of treatment |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Primary diagnosis of nonpsychotic MDD (single or recurrent) for at least 4 weeks before study entry
- In good general medical health
- Normal intelligence
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluoxetineAlso: ProzacParticipants will take 10 to 40 mg per day of fluoxetine for 30 weeks. | Drug | Continued medication alone, Continued medication plus CBT |
| Relapse prevention cognitive behavioral therapy (CBT)Also: CBTAfter 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. | Behavioural | Continued medication plus CBT |
Primary outcome
Time to Remission
Time frame: 30 weeks
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.
Relapse
Time frame: Measured at Weeks 12, 18, 24, and 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.
Remission
Time frame: Measured at Weeks 12, 18, 24, and 30
Remission is defined as CDRS-R <=28.
3 secondary outcomes
K-Life (Time Well)
Time frame: 30 weeks
Remission
Time frame: Weeks 52 and 78
Relapse
Time frame: Weeks 52 and 78
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24935082Kennard 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.
- Derived from this study: PubMed 40520979Croarkin 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.
- Derived from this study: PubMed 26598474Emslie 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.
- Derived from this study: PubMed 24360599Croarkin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Graham J. Emslie, MD principal investigator
University of Texas, Southwestern Medical Center at Dallas
Beth D. Kennard, PsyD principal investigator
University of Texas, Southwestern Medical Center at Dallas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fluoxetine and Relapse prevention cognitive behavioral therapy (CBT) in people with Depression, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Remission (time frame: 30 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00612313, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2016.