Mood Stabilizer (MS)+ Antidepressant vs MS + Placebo in Maintenance of Bipolar Disorder.
Condition: Bipolar I Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      Patients with bipolar I disorder (BD) experience depression 3 times more frequently than
      mania, and antidepressants are prescribed as adjuncts to mood stabilizers in up to 70% of
      patients. However, no placebo-controlled trials have assessed the efficacy or safety of
      modern antidepressants in combination with mood stabilizers in the maintenance treatment of
      BD. The investigators propose a multicentre, randomized, double-blind clinical trial
      comparing mood stabilizer plus antidepressant (escitalopram or bupropion XL) to mood
      stabilizer plus placebo in the maintenance treatment of BD.

      The investigators hypothesize that in clinically representative patients with bipolar
      disorder, who respond to acute treatment with a newer antidepressant medication in
      conjunction with a mood stabilizing medication, continuing the antidepressant for 12 months
      will reduce the risk of relapse into any mood episode, including depression, mania, and
      hypomania, compared to stopping the antidepressant after 8 weeks.
    

Detailed description: 
      Study Design:

      The investigators propose a multicentre, randomized, double-blind, placebo-controlled trial
      in patients with BD who are currently experiencing a depressive episode. The trial will
      consist of two phases: an open-label acute treatment phase, and a double-blind maintenance
      treatment phase.

      OPEN-LABEL ACUTE TREATMENT PHASE

      Experimental Design Patients with BD depression who are receiving treatment with antimanic
      medication(s), defined as: 1) a mood stabilizer (lithium or divalproex ), 2) a
      second-generation antipsychotic (SGA) (risperidone, olanzapine, quetiapine, aripiprazole, or
      ziprasidone), or 3) combination anti-manic therapy (two mood stabilizers; or a mood
      stabilizer plus an SGA (the SGA asenapine will also be permitted if prescribed with a mood
      stabilizer); or a mood stabilizer or SGA plus lamotrigine), will have open-label escitalopram
      10-30 mg/day or bupropion XL 150-450 mg/day added to their medication(s) for up to 16
      weeks.Patients who complete at least 4 weeks of treatment and achieve remission from their
      index depression which is maintained for ≥ 2 weeks will be eligible to enter the double-blind
      study phase. The duration of treatment in the open-label phase will be 4-16 weeks, depending
      on the time required to achieve remission.

      DOUBLE-BLIND MAINTENANCE TREATMENT PHASE

      Patients who are in remission from their index depression for ≥ 2 weeks and ≤ 8 weeks are
      eligible to take part in the double-blind maintenance phase. There are two routes to enter
      the double-blind phase:

        -  following completion of the open-label phase, or

        -  following a period of clinical treatment, not exceeding 16 weeks, with the same
           medications used in the open-label phase. Patients who respond to clinical treatment
           with carbamazepine plus an antidepressant may also enter the double-blind phase.

      Experimental Design

      During the double-blind phase, all patients will continue treatment with their anti-manic
      medication(s) and will be randomized to one of two treatment arms for up to 52 weeks:

        -  Patients randomized to the "8 week arm" will discontinue antidepressant treatment after
           8 weeks, as recommended in current clinical practice guidelines..

        -  Patients randomized to the "52 week arm" will continue treatment with their
           antidepressant medication for 52 weeks, or until withdrawal from the study.
    

Intervention name(s): Escitalopram; Wellbutrin XL
Intervention type(s): Drug; Drug
Intervention description(s): Escitalopram will be prescribed in the dose range 10-30 mg daily.
In patients randomized to the "8-week group", escitalopram will be tapered, discontinued, and replaced with placebo over a period of 2 weeks, beginning at the week 6 study visit.
The dose of escitalopram (or matching placebo) may be decreased in 10 mg increments only in the case of intolerable side effects. The dose must remain within the protocol-defined range of 10-30 mg daily at all time points.; Bupropion XL will be prescribed in the dosage range 150-450 mg daily.
In patients randomized to the "8-week group", bupropion XL will be tapered, discontinued, and replaced with placebo over a period of 2 weeks, beginning at the week 6 study visit.
The dose of bupropion XL (or matching placebo) may be decreased in 150 mg increments only in the case of intolerable side effects. The dose must remain within the protocol-defined range of 150-450 mg daily at all time points.
Other intervention name(s): Lexapro/Cipralex; Wellbutrin
Intervention MeSH terms: Bupropion; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bipolar I disorder; Depression; Antidepressant