Trial Outcomes & Findings for Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse (NCT NCT00612313)

NCT ID: NCT00612313

Last Updated: 2016-01-07

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 144 participants
• Primary outcome timeframe: 30 weeks
• Results posted on: 2016-01-07

Participant Flow

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.

Participant milestones

Measure	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.	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.
Overall Study STARTED	69	75
Overall Study COMPLETED	52	62
Overall Study NOT COMPLETED	17	13

Reasons for withdrawal

Measure	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.	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.
Overall Study Withdrawal by Subject	6	9
Overall Study Lost to Follow-up	11	4

Baseline Characteristics

Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse

Baseline characteristics by cohort

Measure	Continued Medication Alone n=69 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants will take 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=75 Participants 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.	Total n=144 Participants Total of all reporting groups
Age, Continuous	14.2 Years STANDARD_DEVIATION 2.4 • n=5 Participants	13.5 Years STANDARD_DEVIATION 2.7 • n=7 Participants	13.8 Years STANDARD_DEVIATION 2.6 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	38 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	37 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	23 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants n=5 Participants	52 Participants n=7 Participants	101 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants	64 Participants n=7 Participants	118 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	69 participants n=5 Participants	75 participants n=7 Participants	144 participants n=5 Participants
Baseline CDRS-R	59.2 units on a scale STANDARD_DEVIATION 7.0 • n=5 Participants	56.8 units on a scale STANDARD_DEVIATION 7.1 • n=7 Participants	58.0 units on a scale STANDARD_DEVIATION 7.2 • n=5 Participants
Baseline CGI Severity	5.3 units on a scale STANDARD_DEVIATION 0.69 • n=5 Participants	5.1 units on a scale STANDARD_DEVIATION 0.7 • n=7 Participants	5.2 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Continued Medication Alone n=69 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=75 Participants 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.
Time to Remission	13.67 weeks Standard Error 1.17	11.33 weeks Standard Error 0.95

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Continued Medication Alone n=52 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=64 Participants 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.
Relapse Week 30	26.5 probability of relapse (%)	9 probability of relapse (%)
Relapse Week 12	3 probability of relapse (%)	1 probability of relapse (%)
Relapse Week 18	10 probability of relapse (%)	3.5 probability of relapse (%)
Relapse Week 24	20.5 probability of relapse (%)	7 probability of relapse (%)

PRIMARY outcome

Timeframe: Measured at Weeks 12, 18, 24, and 30

Remission is defined as CDRS-R <=28.

Outcome measures

Measure	Continued Medication Alone n=69 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=75 Participants 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.
Remission Week 12	59 probability of remitting (%)	68 probability of remitting (%)
Remission Week 18	71 probability of remitting (%)	79 probability of remitting (%)
Remission Week 24	80 probability of remitting (%)	86 probability of remitting (%)
Remission Week 30	84 probability of remitting (%)	90 probability of remitting (%)

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Continued Medication Alone n=69 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=75 Participants 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.
K-Life (Time Well)	12.8 Weeks spent well Standard Deviation 9.5	16.0 Weeks spent well Standard Deviation 9.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Continued Medication Alone n=69 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=75 Participants 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.
Remission Week 52	89 Probability of remission (%)	94 Probability of remission (%)
Remission Week 78	92 Probability of remission (%)	96 Probability of remission (%)

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Continued Medication Alone n=54 Participants Participants received antidepressant treatment with fluoxetine for 30 weeks Fluoxetine: Participants took 10 to 40 mg per day of fluoxetine for 30 weeks.	Continued Medication Plus CBT n=67 Participants 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.
Relapse Week 52	49 Probability of Relapse (%)	27 Probability of Relapse (%)
Relapse Week 78	62 Probability of Relapse (%)	36 Probability of Relapse (%)

Adverse Events

Continued Medication Alone

Serious events: 7 serious events

Other events: 0 other events

Deaths: 0 deaths

Continued Medication Plus CBT

Serious events: 9 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Continued Medication Alone n=69 participants at risk 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	Continued Medication Plus CBT n=75 participants at risk 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
Psychiatric disorders Hospitalization for Suicide Attempt	1.4% 1/69 • Number of events 1	0.00% 0/75
Psychiatric disorders Hospitalization for Suicidal Ideation	4.3% 3/69 • Number of events 3	6.7% 5/75 • Number of events 5
Psychiatric disorders Hospitalization for Agitation	1.4% 1/69 • Number of events 1	0.00% 0/75
General disorders Hospitalization for medical conditions	2.9% 2/69 • Number of events 2	4.0% 3/75 • Number of events 5
Psychiatric disorders Suicidal behavior that did not result in hospitalization	0.00% 0/69	1.3% 1/75 • Number of events 1

Other adverse events

Adverse event data not reported

Additional Information

Dr. Graham Emslie and Dr. Betsy Kennard

UT Southwestern Medical Center

Phone: 214-456-5900

Email: beth.kennard@utsouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place