VA Augmentation and Switching Treatments for Improving Depression Outcomes
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: Switching: Bupropion-SR; Augmenting: Antidepressant + Bupropion-SR; Augmenting: Antidepressant + Aripiprazole
Intervention description: Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.; Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment, or adjust depending on response or side effect profile for up to 36 weeks.
And
Bupropion-SR (Dose: 150 mg - 400 mg taken per day orally for up to 36 weeks): Initiating with bupropion-SR dose of 150 mg, then increasing dose per protocol up to 400 mg (200 mg BID), maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.; Current antidepressant (either a SSRI or a SNRI or mirtazapine): Continue the dose prescribed at time of enrollment or adjust depending on response or side effect profile for up to 36 weeks.
And
Aripiprazole (Dose: 2 mg - 15 mg taken orally once per day for up to 36 weeks): Initiating with aripiprazole dose of 2 mg for one week, then increasing dose per protocol up to 15 mg, maintaining or decreasing dose for up to 36 weeks depending on response and side effect profile through the acute and continuation phases.
Intervention MeSH terms: Aripiprazole; Bupropion; Antidepressive Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1522.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Mood Disorder; Depression; Depressive Disorder; Depressive Disorder, Major; Bupropion; Aripiprazole; Remission; Relapse; Cost-Effectiveness; Atypical Antipsychotic; Antidepressant; Augmentation; Veterans; Mental Health

Summary:

      The overall purpose is to determine research based 'next-steps' for outpatients with major
      depressive disorder who have not had satisfactory outcomes to standard 'first-step'
      treatments. The primary objective is to compare the acute (up to 12 weeks) treatment
      effectiveness of augmenting an antidepressant with aripiprazole or with bupropion-slow
      release (SR) vs. switching treatment to bupropion-SR monotherapy on symptom remission in
      Veterans with Major Depressive Disorder (MDD) who have not achieved optimal response after an
      adequate trial on antidepressant (a selective serotonin reuptake inhibitor [SSRI] or
      serotonin and norepinephrine reuptake inhibitor [SNRI] or mirtazapine) monotherapy. The
      secondary objectives are to compare the acute (up to 12 weeks) and long term (up to 36 weeks)
      efficacy, safety, effects on functioning, suicidality, quality of life, anxiety and other
      associated symptoms, costs and cost-effectiveness of each of the three treatments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  DSM-IV diagnosis of single or recurrent, non-psychotic, major depressive disorder

          -  Currently taking a selective serotonin reuptake inhibitor (SSRI) or
             serotonin-norepinephrine reuptake inhibitor (SNRI) or mirtazapine for major depressive
             disorder

          -  Need for "next-step" treatment based on documented suboptimal outcome from current
             antidepressant treatment for major depressive episode (at least 6 weeks treatment with
             a QIDS-C16 >= 16 or at least 8 weeks with a QIDS-C16 >= 11; and at least 3 weeks at a
             stable "optimal" dose

          -  Age: 18 years of age or older

        Exclusion Criteria:

          -  Prior inadequate response after an adequate treatment trial or clear cut intolerance
             to either of the study medications (aripiprazole or bupropion)

          -  Current treatment with bupropion, aripiprazole or any other antipsychotic agent

          -  Lifetime history of bipolar disorder, schizophrenia, schizoaffective disorder, or
             psychosis not otherwise specified

          -  Current diagnosis of Dementia

          -  Current diagnosis of an eating disorder or a seizure disorder

          -  High suicide risk currently requiring acute intervention (other than outpatient
             treatment of depression)

          -  Unstable, serious medical condition or one requiring acute medical treatment, or
             anticipation of hospitalization for extended care

          -  Requiring immediate hospitalization for psychiatric disorders

          -  Physiologic substance dependence requiring detoxification (excluding nicotine) in the
             past 30 days (substance abuse is not an exclusion criteria)

          -  Taking any concomitant medication that contraindicates any of treatment options or
             augmenting agents known to have an antidepressant effect

          -  Concurrent or recent participation (within the last 30 days) in another conflicting
             clinical trial with a mental health, investigational drug, or medical device
             intervention

          -  Female - pregnant or lactating or planning to become pregnant

          -  Patient was not able or willing to provide informed consent; or changed mind about
             participating prior to randomization

          -  Patient was not referred to the study