Major Depressive Disorder
Conditions
Keywords
Depression, Major Depressive Disorder, Escitalopram
Brief summary
This is a short-term study to evaluate the efficacy, safety, and tolerability of escitalopram in adult patients (18 to 65 years of age) with moderate to severe depression. Patients completing the study may be eligible to enter a long-term open-label extension study with escitalopram.
Interventions
DRUGEscitalopram
Escitalopram low dose, oral administration, once daily dosing for 8 weeks.
DRUGPlacebo
Placebo, oral administration, once daily dosing for 8 weeks
Sponsors
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients must meet Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for Major Depressive Disorder. * The patient's current depressive episode must be at least 8 weeks in duration.
Exclusion criteria
* Women who are pregnant, women who will be breastfeeding during the study, and women with childbearing potential who are not practicing a reliable method of birth control. * Patients with a history of meeting DSM-IV-TR criteria for: a. any manic or hypomanic episode; b. schizophrenia or any other psychotic disorder; c. obsessive-compulsive disorder. * Patients who are considered a suicide risk * Patients with a history of seizures (including seizure disorder), stroke, significant head injury, central nervous system tumors, or any other condition that predisposes patients to a risk for seizure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Total Montgomery Asberg Depression Rating Scale (MADRS) at 8 Weeks. | Change from baseline in MADRS total score at week 8 | The MADRS is a 10-item clinician-rated scale that was used to assess depressive symptomatology over the patient's prior week. Patients were rated on 10 items designed to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point Likert scale; a score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The total score range is 0 to 60 (higher score indicates a greater severity of symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hamiltion Rating Scale for Depression (HAM-D) at Week 8 | Change from baseline in HAM-D at week 8 | The HAMD is a clinician-rated 24-item scale was used to rate the patient's depressive state. It was also used to identify obsessive-compulsive, genital, and somatic symptoms, as well as diurnal variation in the presence of symptoms. Each item was scored on a 3, 4 or 5-point Likert scale. A score of 0 indicated the absence of symptoms, and a score of 2, 3 or 4 indicated symptoms of maximum severity. The total score range is 0 to 74 (higher score indicates a greater depressive state). |
Countries
United States
Participant flow
Recruitment details
Recruitment period was from 4/30/08 through 12/19/08 with last patient last visit on 2/24/09 at 45 centers in the US.
Pre-assignment details
A one-week single-blind placebo period was completed prior to randomization. Patients were then randomized in a 3:3:2 ratio to either escitalopram low dose, escitalopram high dose or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram Low Dose Escitalopram low dose, administered orally (QD \[once a day\]) for 8 weeks of stable dose treatment phase. The Overall Number of Baseline Participants is based on the Safety population. | 322 |
| Escitalopram High Dose Escitalopram high dose, administered orally (QD \[once a day\]) for 8 weeks of stable dose treatment phase. The Overall Number of Baseline Participants is based on the Safety population. | 324 |
| Placebo Placebo, administered orally (QD \[once a day\]) for 8 weeks of stable dose treatment phase. The Overall Number of Baseline Participants is based on the Safety population. | 218 |
| Total | 864 |
Baseline characteristics
| Characteristic | Escitalopram High Dose | Placebo | Escitalopram Low Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 324 Participants | 218 Participants | 322 Participants | 864 Participants |
| Age Continuous | 40.4 years STANDARD_DEVIATION 11.9 | 42.3 years STANDARD_DEVIATION 12.7 | 41.4 years STANDARD_DEVIATION 12.3 | 41.3 years STANDARD_DEVIATION 12.2 |
| Region of Enrollment United States | 324 participants | 218 participants | 322 participants | 864 participants |
| Sex: Female, Male Female | 222 Participants | 137 Participants | 205 Participants | 564 Participants |
| Sex: Female, Male Male | 102 Participants | 81 Participants | 117 Participants | 300 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 146 / 322 | 160 / 324 | 74 / 218 |
| serious Total, serious adverse events | 3 / 322 | 7 / 324 | 4 / 218 |
Outcome results
Primary
Change From Baseline in Total Montgomery Asberg Depression Rating Scale (MADRS) at 8 Weeks.
The MADRS is a 10-item clinician-rated scale that was used to assess depressive symptomatology over the patient's prior week. Patients were rated on 10 items designed to assess feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and lack of interest. Each item was scored on a 7-point Likert scale; a score of 0 indicated the absence of symptoms, and a score of 6 indicated symptoms of maximum severity. The total score range is 0 to 60 (higher score indicates a greater severity of symptoms).
Time frame: Change from baseline in MADRS total score at week 8
Population: The analysis was performed on the intent to treat population based on the LOCF approach using an ANCOVA model with treatment group and study center as factors and the baseline MADRS total score as a covariate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram Low Dose | Change From Baseline in Total Montgomery Asberg Depression Rating Scale (MADRS) at 8 Weeks. | -12.8 Units on a scale | Standard Error 0.6 |
| Escitalopram High Dose | Change From Baseline in Total Montgomery Asberg Depression Rating Scale (MADRS) at 8 Weeks. | -13.4 Units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in Total Montgomery Asberg Depression Rating Scale (MADRS) at 8 Weeks. | -10.1 Units on a scale | Standard Error 0.7 |
Secondary
Change From Baseline in Hamiltion Rating Scale for Depression (HAM-D) at Week 8
The HAMD is a clinician-rated 24-item scale was used to rate the patient's depressive state. It was also used to identify obsessive-compulsive, genital, and somatic symptoms, as well as diurnal variation in the presence of symptoms. Each item was scored on a 3, 4 or 5-point Likert scale. A score of 0 indicated the absence of symptoms, and a score of 2, 3 or 4 indicated symptoms of maximum severity. The total score range is 0 to 74 (higher score indicates a greater depressive state).
Time frame: Change from baseline in HAM-D at week 8
Population: The analysis was performed on the intent to treat population based on the LOCF approach using an ANCOVA model with treatment group and study center as factors and the baseline HAMD total score as a covariate.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Escitalopram Low Dose | Change From Baseline in Hamiltion Rating Scale for Depression (HAM-D) at Week 8 | -11.5 Units on a scale | Standard Error 0.5 |
| Escitalopram High Dose | Change From Baseline in Hamiltion Rating Scale for Depression (HAM-D) at Week 8 | -11.6 Units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline in Hamiltion Rating Scale for Depression (HAM-D) at Week 8 | -8.5 Units on a scale | Standard Error 0.6 |