Depression
Conditions
Keywords
Major Depressive Disorder, MDD, Children, Adolescents, Antidepressant, CBT
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.
Interventions
DRUGFluoxetine
Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.
BEHAVIORALRelapse 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.
Sponsors
National Institute of Mental Health (NIMH)
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Remission | 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 | 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 | Measured at Weeks 12, 18, 24, and 30 | Remission is defined as CDRS-R \<=28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| K-Life (Time Well) | 30 weeks | 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 |
| Remission | Weeks 52 and 78 | 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. |
| Relapse | Weeks 52 and 78 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 69 |
| 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 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. | 75 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 4 |
| Overall Study | Withdrawal by Subject | 6 | 9 |
Baseline characteristics
| Characteristic | Continued Medication Alone | Continued Medication Plus CBT | Total |
|---|---|---|---|
| Age, Continuous | 14.2 Years STANDARD_DEVIATION 2.4 | 13.5 Years STANDARD_DEVIATION 2.7 | 13.8 Years STANDARD_DEVIATION 2.6 |
| Baseline CDRS-R | 59.2 units on a scale STANDARD_DEVIATION 7 | 56.8 units on a scale STANDARD_DEVIATION 7.1 | 58.0 units on a scale STANDARD_DEVIATION 7.2 |
| Baseline CGI Severity | 5.3 units on a scale STANDARD_DEVIATION 0.69 | 5.1 units on a scale STANDARD_DEVIATION 0.7 | 5.2 units on a scale STANDARD_DEVIATION 0.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 23 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 52 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 2 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 64 Participants | 118 Participants |
| Region of Enrollment United States | 69 participants | 75 participants | 144 participants |
| Sex: Female, Male Female | 39 Participants | 38 Participants | 77 Participants |
| Sex: Female, Male Male | 30 Participants | 37 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 69 | 0 / 75 |
| serious Total, serious adverse events | 7 / 69 | 9 / 75 |
Outcome results
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.
Time frame: Measured at Weeks 12, 18, 24, and 30
Population: Only participants who achieved remission were analyzed for relapse rates, as only remitted patients can experience a relapse of depression.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continued Medication Alone | Relapse | Week 12 | 3 probability of relapse (%) |
| Continued Medication Alone | Relapse | Week 24 | 20.5 probability of relapse (%) |
| Continued Medication Alone | Relapse | Week 18 | 10 probability of relapse (%) |
| Continued Medication Alone | Relapse | Week 30 | 26.5 probability of relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 18 | 3.5 probability of relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 12 | 1 probability of relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 30 | 9 probability of relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 24 | 7 probability of relapse (%) |
Primary
Remission
Remission is defined as CDRS-R \<=28.
Time frame: Measured at Weeks 12, 18, 24, and 30
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continued Medication Alone | Remission | Week 12 | 59 probability of remitting (%) |
| Continued Medication Alone | Remission | Week 18 | 71 probability of remitting (%) |
| Continued Medication Alone | Remission | Week 24 | 80 probability of remitting (%) |
| Continued Medication Alone | Remission | Week 30 | 84 probability of remitting (%) |
| Continued Medication Plus CBT | Remission | Week 30 | 90 probability of remitting (%) |
| Continued Medication Plus CBT | Remission | Week 12 | 68 probability of remitting (%) |
| Continued Medication Plus CBT | Remission | Week 24 | 86 probability of remitting (%) |
| Continued Medication Plus CBT | Remission | Week 18 | 79 probability of remitting (%) |
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.
Time frame: 30 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continued Medication Alone | Time to Remission | 13.67 weeks | Standard Error 1.17 |
| Continued Medication Plus CBT | Time to Remission | 11.33 weeks | Standard Error 0.95 |
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
Time frame: 30 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Continued Medication Alone | K-Life (Time Well) | 12.8 Weeks spent well | Standard Deviation 9.5 |
| Continued Medication Plus CBT | K-Life (Time Well) | 16.0 Weeks spent well | Standard Deviation 9.1 |
p-value: 0.02Regression, Poisson
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.
Time frame: Weeks 52 and 78
Population: Only participants who achieved remission were analyzed for relapse rates, as only remitted patients can experience a relapse of depression.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continued Medication Alone | Relapse | Week 52 | 49 Probability of Relapse (%) |
| Continued Medication Alone | Relapse | Week 78 | 62 Probability of Relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 52 | 27 Probability of Relapse (%) |
| Continued Medication Plus CBT | Relapse | Week 78 | 36 Probability of Relapse (%) |
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.
Time frame: Weeks 52 and 78
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Continued Medication Alone | Remission | Week 52 | 89 Probability of remission (%) |
| Continued Medication Alone | Remission | Week 78 | 92 Probability of remission (%) |
| Continued Medication Plus CBT | Remission | Week 52 | 94 Probability of remission (%) |
| Continued Medication Plus CBT | Remission | Week 78 | 96 Probability of remission (%) |