Combining Medications to Enhance Depression Outcomes
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: SSRI + placebo; Escitalopram + Bupropion SR; Venlafaxine XR + Mirtazapine
Intervention description: Participants will take escitalopram (10 - 20 mg/day)+ placebo (1 to 3 pills per day). Medications taken orally. Participants will take escitalopram plus placebo for up to 28 weeks. Dosages were adjusted as need at each clinic visit.; Participant will take Burpopion SR (150 to 450 mg/day) + Escitalopram (10 to 20 mg/day) for up to 28 weeks. Medications taken orally. Bupropion SR was blinded, and escitalopram was given open label. Dosages were adjusted as need at each clinic visit.; Participants will take Venlafaxine XR (75 to 225 mg/day) + Mirtazapine (15 to 45 mg/day) for up to 28 weeks. Medications taken orally. Venlafaxine XR was blinded, and mirtazapine was given open label. Dosages were adjusted as need at each clinic visit.
Intervention MeSH terms: Dexetimide; Mirtazapine; Citalopram; Bupropion; Venlafaxine Hydrochloride; Escitalopram
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 665.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: depression, medication, antidepressant, chronic, recurrent

Summary:

      This study will compare whether a combination of antidepressant medications is better than
      one antidepressant medication alone when given as initial treatment for people with chronic
      or recurrent major depressive disorder.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Seeking treatment at the primary or specialty care site, and be planning to continue
             living in the area of that clinic for the duration of the study

          -  Meets clinical criteria for nonpsychotic MDD, recurrent (with the current episode
             being at least 2 months in duration), or chronic (current episode greater than 2
             years) as defined by a clinical interview and confirmed by the MINI International
             Neuropsychiatric Interview (MINI)

          -  Screening 17 item HRSD score of 16 or greater

          -  Treatment with antidepressant medication combinations is clinically acceptable

          -  Patient with and without current suicidal ideation may be included in the study as
             long as outpatient treatment is clinically appropriate

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Plans to become pregnant over the ensuing 8 months following study entry or are
             sexually active and not using adequate birth control

          -  History (lifetime) of psychotic depression, schizophrenia, bipolar (I, II, or NOS),
             schizoaffective, or other Axis I psychotic disorders

          -  Current psychotic symptom(s)

          -  History (within the last 2 years before study entry) of anorexia or bulimia

          -  Current primary diagnosis of obsessive compulsive disorder

          -  Current substance dependence that requires inpatient detoxification or inpatient
             treatment

          -  Requiring immediate hospitalization for a psychiatric disorder

          -  Definite history of intolerance or allergy (lifetime) to any protocol medication

          -  History of clear nonresponse to an adequate trial of an FDA-approved monotherapy in
             the current MDE if recurrent, or during the last 2 years before study entry if chronic

          -  History of clear nonresponse to an adequate trial of any study medication used as a
             monotherapy, or to one or more of the protocol combinations in the current or any
             prior MDE

          -  Currently taking any of the study medications at any dose

          -  Having taken Prozac (fluoxetine) or an MAOI in the 4 weeks before study entry

          -  Presence of an unstable general medical condition (GMC) that will likely require
             hospitalization or to be deemed terminal (life expectancy less than 6 months after
             study entry)

          -  Currently taking medications or have GMCs that contraindicate any study medications
             (e.g., seizure disorder)

          -  Requiring medications for GMCs that contraindicate any study medication

          -  Epilepsy or other conditions requiring an anticonvulsant

          -  Lifetime history of having a seizure including febrile or withdrawal seizures

          -  Receiving or have received vagus nerve stimulation (VNS), electroconvulsive therapy
             (ECT), repetitive transcranial magnetic stimulation (rTMS), or other somatic
             antidepressant treatments

          -  Currently taking or having taken within the 7 days before study entry any of the
             following exclusionary medications: antipsychotic medications, anticonvulsant
             medications, mood stabilizers, or central nervous system stimulants (antidepressant
             medication used for the treatment of depression or other purposes such as smoking
             cessation or pain are excluded since these agents may interfere with the testing of
             the major hypotheses under study)

          -  Uncontrolled narrow angle glaucoma

          -  Taking thyroid medication for hypothyroidism may be included only if stable on the
             medication for 3 months

          -  Using agents within the 7 days before study entry that are potential augmenting agents
             (e.g., T3 in the absence of thyroid disease, SAMe, St. John's Wort, lithium,
             buspirone)

          -  Therapy that is depression-specific