Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Depression, Adolescents, Escitalopram, Pediatrics
Brief summary
Depression affects approximately 2.5% of children and 8% of adolescents. Escitalopram is the S-enantiomer of citalopram. Both escitalopram and citalopram are selective serotonin reuptake inhibitors (SSRIs) and are used to treat depression in adults. This study is designed to provide a systematic evaluation of the safety and efficacy of escitalopram in the treatment of depressed pediatric patients, 12 to 17 years of age. Patients completing the study will be eligible to enter an open-label extension study.
Interventions
DRUGEscitalopram
Escitalopram 10mg per day for three weeks, 10-20mg per day for up to the remaining 5 weeks
DRUGPlacebo
Placebo once daily for up to 8 weeks
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patient must meet Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) diagnostic criteria for Major Depressive Disorder. * Patient's current depressive episode must be at least 12 weeks in duration * Patient must have a parent or caregiver who must agree to accompany the patient to all clinic visits.
Exclusion criteria
* Patients who currently meet DSM-IV criteria for: 1. attention deficit-hyperactivity disorder 2. obsessive-compulsive disorder 3. posttraumatic stress disorder 4. bipolar disorder 5. pervasive developmental disorder 6. mental retardation 7. conduct disorder 8. oppositional defiant disorder * Patients who are considered a suicide risk (have active suicidal ideation), who have made a suicide attempt, or who have ever been hospitalized because of a suicide attempt.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score | Baseline to end of week 8 | Change from baseline to week 8 in Children's Depression Rating Scale total score. The scale measures 17 depressive symptoms, of which 3 are rated 1-5 and 14 are rated 1-7 (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) for a total score range of 17-113. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impressions - Improvement | CGI-I score at the end of Week 8 | Clinical Global Impressions - Improvement score at the end of week 8. The scale rates improvement or worsening of patient mental health relative to baseline on a scale from 1 (very much improved) to 7 (very much worse). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Children's Global Assessment Scale | At baseline and end of week 8 | Change from baseline to week 8 in CGAS score which rates the patient's general level of functioning for the past 14 days on a scale of 1 (most impaired) to 100 (healthiest). |
Countries
United States
Participant flow
Recruitment details
Recruitment period was from April 1, 2005 through March, 2007 at 40 centers in the US.
Pre-assignment details
2 week screening with one-week single-blind placebo. Patients meeting selection criteria at baseline were randomized to once daily escitalopram 10-20mg/day or placebo (1:1).
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram Once daily oral administration of escitalopram tablets - 1 tablet (10mg) for the first three weeks, then 1 tablet (10mg or 20mg) depending on therapeutic response and tolerability. | 155 |
| Placebo Once daily oral administration of placebo tablets | 157 |
| Total | 312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | death of parent | 0 | 1 |
| Overall Study | Lack of Efficacy | 5 | 5 |
| Overall Study | Lost to Follow-up | 8 | 6 |
| Overall Study | moving away from site | 1 | 1 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 9 |
Baseline characteristics
| Characteristic | Placebo | Escitalopram | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 157 Participants | 155 Participants | 312 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 14.5 years STANDARD_DEVIATION 1.5 | 14.7 years STANDARD_DEVIATION 1.6 | 14.6 years STANDARD_DEVIATION 1.6 |
| Region of Enrollment United States | 157 participants | 155 participants | 312 participants |
| Sex: Female, Male Female | 92 Participants | 92 Participants | 184 Participants |
| Sex: Female, Male Male | 65 Participants | 63 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 121 / 155 | 118 / 157 |
| serious Total, serious adverse events | 4 / 155 | 2 / 157 |
Outcome results
Primary
Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score
Change from baseline to week 8 in Children's Depression Rating Scale total score. The scale measures 17 depressive symptoms, of which 3 are rated 1-5 and 14 are rated 1-7 (1 = no symptom difficulties; 5 or 7 = severe clinically significant difficulties) for a total score range of 17-113.
Time frame: Baseline to end of week 8
Population: Efficacy analyses used Intent-To-Treat Population, which consisted of all patients who received at least 1 dose of double-blind study drug \& who had at least 1 post-baseline assessment of the CDRS-R. LOCF technique was used to impute missing data. 1 escitalopram pt. did not have a post-baseline CDRS-R total score.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram | Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score | -22.4 Change in total score at endpoint | Standard Error 1.1 |
| Placebo | Change in Children's Depression Rating Scale - Revised (CDRS-R) Total Score | -18.4 Change in total score at endpoint | Standard Error 1.1 |
Comparison: The null hypothesis is that there is no difference in the Change from Baseline to Week 8 in CDRS-R total score between treatment groups. The power calculation was based on the change from baseline to Week 8 in CDRS-R total score (LOCF approach). Assuming an effect size (treatment group difference relative to standard deviation) of 0.325, a sample size of approximately 150 patients per treatment group was used to provide at least 80% power at a significance level of 0.05 using a two-sided test.p-value: 0.02295% CI: [-6.2, -0.5]ANCOVA
Secondary
Clinical Global Impressions - Improvement
Clinical Global Impressions - Improvement score at the end of week 8. The scale rates improvement or worsening of patient mental health relative to baseline on a scale from 1 (very much improved) to 7 (very much worse).
Time frame: CGI-I score at the end of Week 8
Population: The Intent-To-Treat Population was used. The Last Observation Carried Forward (LOCF) technique was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram | Clinical Global Impressions - Improvement | 2.2 Score on scale | Standard Error 0.1 |
| Placebo | Clinical Global Impressions - Improvement | 2.5 Score on scale | Standard Error 0.1 |
Comparison: Missing values were imputed using the LOCF approach.p-value: 0.00895% CI: [-0.595, 0.092]ANCOVA
Other Pre-specified
Children's Global Assessment Scale
Change from baseline to week 8 in CGAS score which rates the patient's general level of functioning for the past 14 days on a scale of 1 (most impaired) to 100 (healthiest).
Time frame: At baseline and end of week 8
Population: The Intent-To-Treat Population was used. The Last Observation Carried Forward (LOCF) technique was used to impute missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram | Children's Global Assessment Scale | 14.7 Change in score | Standard Error 1 |
| Placebo | Children's Global Assessment Scale | 12.4 Change in score | Standard Error 1 |
Comparison: ANCOVA on the Change from Baseline to Week 8 in CGAS score. The model included treatment and center as factors and baseline score as covariate. Missing values were imputed using the LOCF approach.p-value: 0.10395% CI: [-0.439, 4.777]ANCOVA