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Identifying Factors That Predict Antidepressant Treatment Response

Not Applicable
Completed
Conditions
Depression
Interventions
Behavioral: Cognitive behavioral therapy (CBT)
Registration Number
NCT00360399
Lead Sponsor
Emory University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
344
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EscitalopramEscitalopramParticipants will receive treatment with escitalopram for 12 weeks
DuloxetineDuloxetineParticipants will receive treatment with duloxetine for 12 weeks
CBTCognitive behavioral therapy (CBT)Participants will receive 16 one-hour sessions of cognitive behavioral therapy delivered over 12 weeks
Primary Outcome Measures
NameTimeMethod
Remission From Major Depressive Episode in Intent to Treat SampleUp 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 InterventionMeasured 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 Outcome Measures
NameTimeMethod
Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat SampleUp 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 InterventionMeasured 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 TreatmentMeasured 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 MonotherapyMeasured 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

Trial Locations

Locations (2)

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

Emory University Mood and Anxiety Disorders Program

🇺🇸

Atlanta, Georgia, United States

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