Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Intervention: Sertraline; Placebo; BupropionXL
Intervention description: 50-200mg/day; 1-4 pills per day; 150-450 mg/day
Intervention MeSH terms: Sertraline
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Patients were entered into Stage 1, treated with sertraline (Treatment A) or placebo (Treatment B), and used for the primary analysis which included the identification of potential mediators and moderators of response for these two treatments.
In stage two, responders to Treatment A remained on sertraline, and non-responders were switched to bupropion (Treatment C). Responders to Treatment B remained on placebo, and non-responders were switched to sertraline (Treatment D).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 296.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Depression, Major Depressive Disorder, Mood Disorder

Summary:

      This study will examine multiple carefully selected clinical and biological markers, using
      both existing state-of-the-art technologies as well as pioneering, innovative approaches. The
      study is designed to identify moderators and mediators of treatment response for depression
      in order to specify a biosignature of treatment response for depression. Evaluation of the
      usefulness of these markers in a carefully conducted clinical trial comparing an
      antidepressant to placebo will assist in developing a Depression Treatment Response Index
      (DTRI) to help clinicians match treatments to patients with MDD, resulting in timely
      selection of treatments best suited for individual patients and thus approaching personalized
      treatment. The resulting index provides a truly novel means of synthesizing the contribution
      of key clinical and biological parameters in an easy to use tool for clinical care.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults, age 18-65

          -  Written informed consent obtained

          -  Outpatients with a current primary diagnosis of nonpsychotic recurrent or chronic MDD
             per the SCID-I

          -  QIDS-SR score of ≥ 14 at Screening Visit and Randomization (Baseline) Visit

          -  No failed antidepressant trials of adequate dose and duration, as defined by the
             MGH-ATRQ, in the current episode

          -  Agrees to, and is eligible for, all biomarkers procedures (EEG/psychological testing,
             MRI, and blood draws)

        Exclusion Criteria:

          -  History of inadequate response (to trials at adequate dose for adequate duration) or
             poor tolerability to sertraline (SERT) or bupropion (BUP)

          -  Pregnant or breastfeeding

          -  Plan to become pregnant over the ensuing 12 months following study entry or are
             sexually active and not using adequate contraception

          -  History (lifetime) of psychotic depression, schizophrenia, bipolar (I, II, or NOS)
             disorder, schizoaffective disorder, or other Axis I psychotic disorder

          -  Current primary anxiety disorder diagnosis

          -  Meeting DSM-IV criteria for substance abuse in the last 2 months or substance
             dependence in the last 6 months (except for nicotine)

          -  Require immediate hospitalization for psychiatric disorder

          -  Have an unstable general medical condition (GMC) that will likely require
             hospitalization or to be deemed terminal (life expectancy < 6 months after study
             entry)

          -  Require medications for their GMCs that contraindicate any study medication

          -  Have epilepsy or other conditions requiring an anticonvulsant

          -  Receiving or have received during the index episode vagus nerve stimulation, ECT, or
             rTMS, or other somatic antidepressant treatments

          -  Currently taking any of the following exclusionary medications: antipsychotic
             medications, anticonvulsant medications, mood stabilizers, central nervous system
             stimulants, daily use of benzodiazepines or hypnotics, or antidepressant medication
             used for the treatment of depression or other purposes such as smoking cessation,
             since these agents may interfere with the testing of the major hypotheses under study.
             Nonexcluded concomitant medications are acceptable as long as their clinician
             determines that antidepressant treatment is safe and appropriate.

          -  Significant liver disease that would contraindicate any study medication

          -  Taking thyroid medication for hypothyroidism may be included only if they have been
             stable on the thyroid medication for 3 months

          -  Using agents that are potential augmenting agents (e.g., T3 in the absence of thyroid
             disease, SAMe, St. John's Wort, lithium, buspirone, Omega 3 fatty acids)

          -  Therapy that is depression specific, such as CBT or Interpersonal Psychotherapy of
             Depression (IPT) is not allowed during participation (participants can participate if
             they are receiving psychotherapy that is not targeting the symptoms of depression,
             such as supportive therapy, marital therapy).

          -  Subjects must be fluent in English and have the capacity to understand the nature of
             the study and sign the written informed consent since non-English speaking personnel
             are not available for this study, and the research instruments are not yet translated
             and validated in other languages.

          -  Currently actively suicidal or considered a high suicide risk

          -  Are currently enrolled in another study, and participation in that study
             contraindicates participation in the EMBARC study.

          -  Any reason not listed herein yet, determined by the site PI, medical personnel, or
             designee that constitutes good clinical practice and that would in the opinion of the
             site PI, medical personnel, or designee make participation in the study hazardous.