Bipolar Depression
Conditions
Keywords
Bipolar Depression, Depression, Children, Adolescents, Seroquel, Bipolar Depression in Children and Adolescents
Brief summary
The purpose of this study is to determine if quetiapine fumarate extended-release (quetiapine XR or SEROQUEL® XR) 150 to 300 mg/day taken by itself is effective and safe in treating children or adolescents aged 10 to 17 with bipolar depression and if so, how it compares with placebo (a non-active tablet, like a sugar pill, that looks like quetiapine).
Interventions
DRUGQuetiapine XR
Oral treatment with 150 up to 300 mg/day once daily in the evening
DRUGPlacebo
Oral treatment once daily in the evening
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent by one or both parents or legal guardian and written assent by the patients before any study procedures are performed. * The patient must have a documented clinical diagnosis for bipolar I or bipolar II disorder, and including current episode depressed. * Patients are required to be in outpatient status at the enrollment and randomization visits and believed likely to remain an outpatient for the duration of the study. * Patients must be able to swallow the study medication tablets.
Exclusion criteria
* The patient must not have been diagnosed with Tourette's Disorder, Obsessive-Compulsive Disorder, acute Post-traumatic Stress Disorder, Panic Disorder, Autistic Disorder and/or Asperger's Disorder. * Patient can not have a history of non-response to an adequate treatment to more than 2 antidepressants during the current episode. * The patient must not have received electroconvulsive therapy (ECT) within 30 days before participating in the study. * Patients who in your doctors judgement pose a current suicidal or homicidal risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Children Depression Rating Scale, Revised (CDRS-R) Total Score From Baseline to Final Assessment (Day 57) | Will be scored at all visits. the analysis is the change from baseline to the final assessment at day 57 | Severity of depression in children and adolescents was calculated based on the 17-item CDRS-R scale (3 items scored from 1-5 and 14 items scored from 1-7, with higher scores indicating more severe depression). The 17 item scores are summed to give the total score (total score range 17-113). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Reaching Remission Where Remission is Defined as CDRS-R Total Score ≤28 at Final Assessment (Day 57). | Days 8 to 57 | The number of patients with remission from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113). |
| The Number of Patients With the Response, Where Response is Defined as ≥50% Reduction From Baseline to Final Assessment (Day 57) in CDRS-R Total Score | Days 8 to 57 | The number of patients reaching response from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113). |
| Change From Baseline to Final Assessment (Day 57) in the CGI-BP-S | Change from Baseline to Day 57 | The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity. |
| CGI-BP-C Score at Final Assessment (Day 57) | Change from Baseline to day 57 | The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement. |
| The Proportion of Patients at Final Assessment (Day 57) With Improvement of Overall Bipolar Illness | Day 57 | The proportion of patients with improvement of overall bipolar illness at Day 57 was calculated. Improvement defined as a CGI-BP-C of Much or Very much improved in overall bipolar illness assessment. |
Countries
Colombia, India, Mexico, Serbia, South Africa, Taiwan, United States
Participant flow
Recruitment details
This multicenter study was conducted between 27 January 2009 and 1 November 2010, which included the recall visit. The recall visit occurred from 5 June 2010 till 1 November 2010.
Pre-assignment details
The study had an up to 35-day enrollment period, 8-week double-blind treatment period with 1 of 2 treatment regimens (quetiapine XR 150 to 300 mg/day or placebo), 1-week safety follow-up period, 2- to 4-week safety follow-up period for patients with BP \>95th percentile at completion/discontinuation.
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine XR Quetiapine XR 150 to 300mg once a day | 92 |
| Placebo Matching placebo | 100 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 12 |
| Overall Study | Condition under investigation worsened | 1 | 3 |
| Overall Study | Incorrect Enrollment | 1 | 0 |
| Overall Study | Lack of therapeutic response | 4 | 1 |
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Other 2 | 4 | 1 |
| Overall Study | Safety Reasons | 1 | 0 |
| Overall Study | Severe non-compliance to protocol | 2 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Quetiapine XR | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 2.18 | 14.0 years STANDARD_DEVIATION 2.05 | 14.0 years STANDARD_DEVIATION 2.11 |
| Sex: Female, Male Female | 47 Participants | 48 Participants | 95 Participants |
| Sex: Female, Male Male | 45 Participants | 52 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 92 | 66 / 100 |
| serious Total, serious adverse events | 1 / — | 4 / — |
Outcome results
Primary
Change in the Children Depression Rating Scale, Revised (CDRS-R) Total Score From Baseline to Final Assessment (Day 57)
Severity of depression in children and adolescents was calculated based on the 17-item CDRS-R scale (3 items scored from 1-5 and 14 items scored from 1-7, with higher scores indicating more severe depression). The 17 item scores are summed to give the total score (total score range 17-113).
Time frame: Will be scored at all visits. the analysis is the change from baseline to the final assessment at day 57
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change in the Children Depression Rating Scale, Revised (CDRS-R) Total Score From Baseline to Final Assessment (Day 57) | -29.6 Scores on a scale | Standard Error 1.65 |
| Placebo | Change in the Children Depression Rating Scale, Revised (CDRS-R) Total Score From Baseline to Final Assessment (Day 57) | -27.3 Scores on a scale | Standard Error 1.6 |
Secondary
CGI-BP-C Score at Final Assessment (Day 57)
The CGI-BP-C scale rates how much the patient's illness has improved or worsened compared to the phase immediately preceding treatment and is scored on a scale from 1 to 8 (1=very much improved to 7=very much worse; 8=not applicable). CGI-BP-C scores \>4 indicate worsening, while scores \<4 indicate improvement.
Time frame: Change from Baseline to day 57
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | CGI-BP-C Score at Final Assessment (Day 57) | 2.4 Scores on a scale | Standard Error 0.15 |
| Placebo | CGI-BP-C Score at Final Assessment (Day 57) | 2.6 Scores on a scale | Standard Error 0.15 |
Secondary
Change From Baseline to Final Assessment (Day 57) in the CGI-BP-S
The CGI-BP-S scale rates the severity of the patient's illness at the time of assessment and is scored from 1 to 7 (1=normal, not ill to 7=very severely ill). Higher CGI-BP-S scores indicate greater illness severity.
Time frame: Change from Baseline to Day 57
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR | Change From Baseline to Final Assessment (Day 57) in the CGI-BP-S | -17.2 Scores on a Scale | Standard Error 0.15 |
| Placebo | Change From Baseline to Final Assessment (Day 57) in the CGI-BP-S | -1.35 Scores on a Scale | Standard Error 0.14 |
Secondary
Number of Patients Reaching Remission Where Remission is Defined as CDRS-R Total Score ≤28 at Final Assessment (Day 57).
The number of patients with remission from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113).
Time frame: Days 8 to 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | Number of Patients Reaching Remission Where Remission is Defined as CDRS-R Total Score ≤28 at Final Assessment (Day 57). | 42 participants |
| Placebo | Number of Patients Reaching Remission Where Remission is Defined as CDRS-R Total Score ≤28 at Final Assessment (Day 57). | 34 participants |
Secondary
The Number of Patients With the Response, Where Response is Defined as ≥50% Reduction From Baseline to Final Assessment (Day 57) in CDRS-R Total Score
The number of patients reaching response from Days 8 to 57 was calculated. The CDRS-R is a 17-item scale with 3 items scored from 1-5 and 14 items scored from 1-7, where higher scores indicating more severe depression. The 17 item scores are summed to give the total score (total score range 17-113).
Time frame: Days 8 to 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | The Number of Patients With the Response, Where Response is Defined as ≥50% Reduction From Baseline to Final Assessment (Day 57) in CDRS-R Total Score | 58 participants |
| Placebo | The Number of Patients With the Response, Where Response is Defined as ≥50% Reduction From Baseline to Final Assessment (Day 57) in CDRS-R Total Score | 55 participants |
Secondary
The Proportion of Patients at Final Assessment (Day 57) With Improvement of Overall Bipolar Illness
The proportion of patients with improvement of overall bipolar illness at Day 57 was calculated. Improvement defined as a CGI-BP-C of Much or Very much improved in overall bipolar illness assessment.
Time frame: Day 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR | The Proportion of Patients at Final Assessment (Day 57) With Improvement of Overall Bipolar Illness | 0.522 Proportions |
| Placebo | The Proportion of Patients at Final Assessment (Day 57) With Improvement of Overall Bipolar Illness | 0.40 Proportions |