Identifying Factors That Predict Antidepressant Treatment Response
Identifying Factors That Predict Antidepressant Treatment Response
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.
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.
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)