Sequential Multiple Assignment Treatment for Bipolar Disorder
Condition: Bipolar I Disorder; Bipolar II Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to compare which of the two mood stabilizers (drugs that help to
      steady/stabilize mood in patients with bipolar disorder (BD)), lithium and divalproex, is
      more effective in patients with bipolar disorder over 26 weeks. The study will also compare
      if lithium or divalproex used alone versus lithium or divalproex used with quetiapine versus
      lithium or divalproex used with lamotrigine is more effective when symptoms of depression
      develop.
    

Detailed description: 
      This open methods advancement study will randomize BD patients with clinically significant
      symptoms to treatment with one of two mood stabilizers (MS), lithium [Li] or divalproex
      [Div]. Those who develop protocol defined depression will then be randomized to a MS alone,
      MS + quetiapine [QTP] or MS + lamotrigine [LTG]. A SMART strategy employs a rule for adding
      new treatments based on each patient's current illness state and response during the trial,
      mimicking the adaptive nature of treatment selection which occurs in clinical settings, but
      in a controlled way which allows application of causal inference. By using early indices of
      response to dynamically alter treatment decisions to improve outcome, SMART eliminates
      unmeasured confounders associated with treatment decisions that are not randomized, as occurs
      in data mining exercises and in other non-randomized decisions in studies which randomize one
      variable at baseline. This sequential adaptive design represents a methodological innovation
      in bipolar trial history which will have particular implications for effectiveness studies.

      Specific Aim A.1: Assess the feasibility of a SMART design in the conduct of an effectiveness
      study over 26 weeks in patients with BD (bipolar disorder).

      Aim A.2 Compare the effectiveness of Li to Div as a primary component of treatment for BD
      over 26 weeks.

      Aim A.3: Assess the effectiveness of MS + QTP and MS + LTG versus MS in subjects who develop
      depression.

      A4. Exploratory Aims: 1.Determine the effects of ethnicity, language facility, education and
      stress as moderators of treatment outcomes; 2. Explore the use of novel statistical
      methodologies to more informatively characterize illness trajectories in response to the
      interventions. In the aggregate these aims also will clarify whether the SMART confirms
      results provided by traditional, single point randomized controlled trials (RCTs).
    

Intervention name(s): Lithium; Divalproex; Lamotrigine; Quetiapine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter).; DV will be dosed to attain DV levels of ≥45mg/L.; LM will be incrementally dosed up to 400 mg/day, or, in combination with DV, 200 mg/day. Dosage may be reduced for adverse effects to one half of the target dose.; QT will be started at 50 mg/day and titrated up to 300 mg as tolerated. QT will be discontinued if not tolerated at 100mg/day and the patient will be treated according to guidelines.
Other intervention name(s): Lithium Carbonate; Depakote; Depakote ER; Lamictal; Seroquel
Intervention MeSH terms: Lamotrigine; Valproic Acid; Quetiapine Fumarate; Lithium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment