Depression
Conditions
Keywords
Escitalopram, Duloxetine, Cognitive Behavioral Therapy, PET, fMRI
Brief summary
This study will compare different treatments for depression in order to identify which factors predict effectiveness, and will include a companion study which investigates combining treatments and long term effectiveness.
Detailed description
Major depressive disorder (MDD) is a serious illness that affects a person's body, mood, and thoughts. The symptoms of MDD can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Antidepressant medications and psychotherapy are among the effective treatments for MDD. Individuals often respond to one type of treatment, but not another. Currently, however, doctors have no way of pre-determining which individuals will most benefit from which treatments. In the absence of practical predictors of MDD treatment response, the potential efficacy of existing MDD treatments is limited. This study will identify factors that may predict MDD treatment response by comparing the effectiveness of a selective serotonin reuptake inhibitor (SSRI), a serotonin norepinephrine reuptake inhibitor (SNRI), and cognitive behavioral therapy in people with MDD. Participants in this 14-week, double-blind study will be randomly assigned to receive duloxetine (SNRI), escitalopram (SSRI), or cognitive behavioral therapy. During the first 2 weeks of screening, participants will complete questionnaires, clinician evaluations, an electrocardiogram, a personality assessment, a dexamethasone-corticotropin releasing factor test, a functional magnetic resonance imaging scan and provide blood samples. Upon completion of screening, patients will start the treatment to which they were randomized. Duloxetine and escitalopram are two medications that are approved by the Food and Drug Administration for the treatment of depression. Cognitive behavioral therapy is a talking therapy that is also used to treat depression. All participants assigned to take duloxetine or escitalopram will be seen by a study physician weekly for 6 weeks, and then every other week for the remainder of the study. Participants assigned to cognitive behavioral therapy will attend therapy sessions twice a week for the first 4 weeks, and then once a week for the remainder of the study. The following assessments will be performed for all participants at each visit: vital sign and weight measurements; clinician assessments; and self-report questionnaires. Additionally, blood samples will be taken at three visits through the trial and functional magnetic resonance imaging (fMRI) scans will be performed at selected times. A companion study to the main CIDAR study offers participants further treatment. Participants who achieve remission after the initial 12 weeks of treatment will have the option to enroll in a 21-month follow-up study of maintenance treatment, with visits every three months to monitor for sustained response and relapse. Participants who do not remit will have the option to enroll in another 12-week treatment course, receiving a combination of CBT and medication. Participants who achieve response after this combination treatment will be eligible to receive maintenance combination treatment for up to an additional 18 months, monitored for sustained response and relapse. Participants who do not wish to enroll or continue in the companion study will be provided with a referral for treatment with another mental health provider.
Interventions
DRUGEscitalopram
Escitalopram 10 to 20 mg per day for 12 weeks
DRUGDuloxetine
Duloxetine 30 to 60 mg per day for 12 weeks
BEHAVIORALCognitive behavioral therapy (CBT)
CBT will include 16 one-hour sessions provided over 12 weeks.
Sponsors
National Institute of Mental Health (NIMH)
Emory University
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
* Current DSM-IV diagnosis of major depressive episode, as determined by Structured Clinical Interview for DSM-IV (SCID-IV) * Primary diagnosis of MDD, based on prominence of symptoms and target for intervention (comorbid anxiety disorders, except obsessive-compulsive disorder (OCD), will not be criteria for exclusion) * Score of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D17) * Agrees to use an effective form of contraception and/or double barrier method
Exclusion criteria
* Previously treated for major depression with either medication or psychotherapy * Current psychosis, dementia, eating disorder, or dissociative disorder * History of bipolar disorder (I and II) or schizophrenia * Alcohol or drug dependence within 3 months prior to study entry or current alcohol or drug abuse (excluding nicotine and caffeine), as assessed by medical history and urine drug screening * Requires neuroleptic or mood stabilizer therapy in addition to depression treatment * Presence of any acute or chronic medical disorder that could affect successful completion of the trial * Medical contraindications that would preclude treatment with escitalopram or duloxetine * Presence of practical issues that would likely prevent completion of the study (e.g., planned geographical relocation) * Pregnant or breastfeeding * Medical conditions that could prevent the safe use of MRI (e.g., pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, or other implants; steel worker) * Medical conditions that could prevent the safe completion of a dexamethasone-corticotropin releasing factor (Dex-CRF) test (e.g., uncontrolled hypertension, significant abnormalities in EKG, anemia, known allergies against drugs)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission From Major Depressive Episode in Intent to Treat Sample | Up to 12 Weeks | The percentage of participants who achieved remission from a major depressive episode, using a last observation carried forward (LOCF) dataset, defined as all randomized patients who initiated treatment and had at least one follow-up rating assessment. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) at the last observation was considered to be remission from depression. |
| Remission From Major Depressive Episode Among Participants Who Completed the Intervention | Measured at Weeks 10 and 12 | The percentage of participants who achieved remission from a major depressive episode. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) after 10 weeks and 12 weeks of the assigned study treatment was considered to be remission from depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Up to 12 Weeks | Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the last observation: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7 |
| Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Measured at Weeks 10 and 12 | Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the Week 10 and Week 12 visits: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7 |
| Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | Measured at 6, 9, 12, 15, 18, 21, and 24 months | The number of participants experiencing a recurrence of depression after they had been in remission with the monotherapy treatment they were randomized to receive. |
| Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy | Measured after 12 weeks of combined treatment | The number of participants achieving remission from major depressive episode after 12 weeks of combined treatment consisting of antidepressant plus cognitive behavioral therapy (CBT) treatments. Those originally randomized to receive one of the antidepressants remained on that medication and had CBT sessions added. Participants originally randomized to CBT had escitalopram added at a dose of 10 to 20 mg per day for 12 weeks |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through the Emory University Mood and Anxiety Disorders Program. Men and women, aged 18-65, meeting DSM-IV criteria for a current major depressive disorder, and who had not received prior treatment for a mood disorder were eligible. 515 consented to participate in the trial and 344 were randomized to a treatment arm.
Pre-assignment details
A total of 344 participants were randomized as follows: 114 randomized to the Escitalopram arm 115 randomized to the Duloxetine arm 115 randomized to the Cognitive behavioral therapy (CBT) arm 28 participants did not return for a post-randomization assessment, resulting in 316 participants with data to analyze.
Participants by arm
| Arm | Count |
|---|---|
| Escitalopram Participants were randomized to receive treatment with escitalopram for 12 weeks, at a dose of 10 to 20 mg per day | 114 |
| Duloxetine Participants were randomized to receive treatment with duloxetine for 12 weeks, at a dose of 30 to 60 mg per day | 115 |
| Cognitive Behavioral Therapy (CBT) Participants were randomized to receive 16 one-hour sessions of cognitive behavioral therapy (CBT) delivered over 12 weeks | 115 |
| Total | 344 |
Baseline characteristics
| Characteristic | Escitalopram | Duloxetine | Cognitive Behavioral Therapy (CBT) | 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 | 114 Participants | 115 Participants | 115 Participants | 344 Participants |
| Age, Continuous | 41.6 years STANDARD_DEVIATION 12.1 | 38.3 years STANDARD_DEVIATION 11.4 | 40.0 years STANDARD_DEVIATION 11.3 | 40.0 years STANDARD_DEVIATION 11.7 |
| Chronic Episode of Depression (2 or More Years) No | 83 participants | 78 participants | 77 participants | 238 participants |
| Chronic Episode of Depression (2 or More Years) Yes | 31 participants | 37 participants | 38 participants | 106 participants |
| Current Anxiety Disorder No | 47 participants | 48 participants | 44 participants | 139 participants |
| Current Anxiety Disorder Yes | 67 participants | 67 participants | 71 participants | 205 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants | 34 Participants | 32 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 81 Participants | 83 Participants | 242 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| History of Suicide Attempt No | 110 participants | 102 participants | 107 participants | 319 participants |
| History of Suicide Attempt Yes | 4 participants | 13 participants | 8 participants | 25 participants |
| Previous Episode(s) of Depression None | 2 participants | 0 participants | 3 participants | 5 participants |
| Previous Episode(s) of Depression One | 59 participants | 51 participants | 67 participants | 177 participants |
| Previous Episode(s) of Depression Three or more | 33 participants | 38 participants | 28 participants | 99 participants |
| Previous Episode(s) of Depression Two | 20 participants | 26 participants | 17 participants | 63 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 23 Participants | 13 Participants | 64 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 39 Participants | 36 Participants | 41 Participants | 116 Participants |
| Race (NIH/OMB) White | 47 Participants | 56 Participants | 61 Participants | 164 Participants |
| Region of Enrollment United States | 114 participants | 115 participants | 115 participants | 344 participants |
| Sex: Female, Male Female | 64 Participants | 68 Participants | 64 Participants | 196 Participants |
| Sex: Female, Male Male | 50 Participants | 47 Participants | 51 Participants | 148 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 | 100 / 114 | 108 / 115 | 70 / 115 |
| serious Total, serious adverse events | 6 / 114 | 3 / 115 | 1 / 115 |
Outcome results
Primary
Remission From Major Depressive Episode Among Participants Who Completed the Intervention
The percentage of participants who achieved remission from a major depressive episode. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) after 10 weeks and 12 weeks of the assigned study treatment was considered to be remission from depression.
Time frame: Measured at Weeks 10 and 12
Population: This population includes participants who completed the trial, per study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Remission From Major Depressive Episode Among Participants Who Completed the Intervention | 44.2 percentage of participants |
| Duloxetine | Remission From Major Depressive Episode Among Participants Who Completed the Intervention | 51.9 percentage of participants |
| Cognitive Behavioral Therapy (CBT) | Remission From Major Depressive Episode Among Participants Who Completed the Intervention | 43.5 percentage of participants |
Primary
Remission From Major Depressive Episode in Intent to Treat Sample
The percentage of participants who achieved remission from a major depressive episode, using a last observation carried forward (LOCF) dataset, defined as all randomized patients who initiated treatment and had at least one follow-up rating assessment. A score of equal to or greater than 7 on the Hamilton Depression Rating Scale (HDRS) at the last observation was considered to be remission from depression.
Time frame: Up to 12 Weeks
Population: This population consists of all participants who were randomized and returned for at least one study visit. This population was used for the intent to treat analyses and not all of these individuals completed the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Remission From Major Depressive Episode in Intent to Treat Sample | 46.7 percentage of participants |
| Duloxetine | Remission From Major Depressive Episode in Intent to Treat Sample | 54.7 percentage of participants |
| Cognitive Behavioral Therapy (CBT) | Remission From Major Depressive Episode in Intent to Treat Sample | 41.9 percentage of participants |
Secondary
Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy
The number of participants achieving remission from major depressive episode after 12 weeks of combined treatment consisting of antidepressant plus cognitive behavioral therapy (CBT) treatments. Those originally randomized to receive one of the antidepressants remained on that medication and had CBT sessions added. Participants originally randomized to CBT had escitalopram added at a dose of 10 to 20 mg per day for 12 weeks
Time frame: Measured after 12 weeks of combined treatment
Population: Participants who did not achieve remission during monotherapy were offered 12 weeks of combination therapy. This sample consists of those participants who consented for the combination therapy part of the trial and who completed the 12 weeks of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Escitalopram | Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy | 22 participants |
| Duloxetine | Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy | 10 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy | 18 participants |
Secondary
Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment
The number of participants experiencing a recurrence of depression after they had been in remission with the monotherapy treatment they were randomized to receive.
Time frame: Measured at 6, 9, 12, 15, 18, 21, and 24 months
Population: This population is comprised of participants who completed 12 weeks of treatment, achieved remission, and participated in a follow-up phase that lasted for up to 21 months or until recurrence occurred.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 24 Months | 3 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 6 Months | 0 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 9 Months | 1 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 12 Months | 1 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 15 Months | 1 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 18 Months | 2 participants |
| Escitalopram | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 21 Months | 3 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 21 Months | 5 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 12 Months | 2 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 15 Months | 4 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 24 Months | 5 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 18 Months | 4 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 6 Months | 0 participants |
| Duloxetine | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 9 Months | 2 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 24 Months | 5 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 18 Months | 5 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 12 Months | 3 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 21 Months | 5 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 9 Months | 1 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 15 Months | 5 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment | 6 Months | 1 participants |
Secondary
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention
Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the Week 10 and Week 12 visits: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7
Time frame: Measured at Weeks 10 and 12
Population: This population includes participants who completed the trial, per study protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Non-Response | 15 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Partial Response | 10 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Response without remission | 23 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Remission | 38 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Remission | 41 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Non-Response | 10 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Response without remission | 16 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Partial Response | 12 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Remission | 30 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Partial Response | 13 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Response without remission | 11 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention | Non-Response | 15 participants |
Secondary
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample
Four mutually exclusive categorical outcomes were defined based on the last valid Hamilton Depression Rating Scale (HDRS) rating at the last observation: 1. Non-response: \<30% reduction from baseline 2. Partial Response: 30-49% reduction from baseline 3. Response without remission: ≥50% reduction from baseline, but HDRS-17 score \>7 4. Remission: HDRS score ≤7
Time frame: Up to 12 Weeks
Population: The population is defined as all randomized patients who initiated treatment and had at least one follow-up rating assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Non-Response | 26 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Partial Response | 12 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Response without remission | 18 participants |
| Escitalopram | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Remission | 49 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Remission | 58 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Non-Response | 21 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Response without remission | 11 participants |
| Duloxetine | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Partial Response | 16 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Remission | 44 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Partial Response | 19 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Response without remission | 10 participants |
| Cognitive Behavioral Therapy (CBT) | Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample | Non-Response | 32 participants |