Identifying Factors That Predict Antidepressant Treatment Response

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)