Comparing treatments for bipolar depression in adults

Sequential Multiple Assignment Randomized Trial for Bipolar Depression

Phase 4 Interventional Massachusetts General Hospital · NCT06433635

This study is testing four different treatments for adults with Bipolar I Disorder who are dealing with a major depressive episode to see which one works best over a year.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment2726 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorMassachusetts General Hospital Academic / other
Locations17 sites (Birmingham, Alabama and 16 other locations)
Trial IDNCT06433635 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness of four treatments for adults with Bipolar I Disorder experiencing a major depressive episode. It employs a Sequential Multiple Assignment Randomized Trial (SMART) design, allowing for re-randomization of participants who do not respond to initial treatments. The study will recruit 2726 participants across multiple sites and follow them for 52 weeks to assess treatment outcomes. The interventions include three FDA-approved medications and a combination therapy that is commonly used but not FDA-approved.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with a diagnosis of Bipolar I Disorder currently experiencing a major depressive episode.

Not a fit: Patients currently experiencing a manic episode or those with a history of rapid cycling or nonaffective psychosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could identify the most effective treatment options for managing bipolar depression, improving patient outcomes.

How similar studies have performed: Other studies have shown promise in comparing treatment effectiveness for bipolar depression, but this specific approach using a SMART design is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Aged between 18 years to 75 years
2. Meets criteria for DSM-V Bipolar I disorder with a history of manic episodes and current major depressive episode lasting at least 6 weeks
3. Can be managed as an outpatient and participate in the study
4. Willing to be randomized; able to perform study assessments
5. Women of childbearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence; Depo Provera is acceptable if it is started 3 months prior to enrollment), and inform staff of their plans to conceive.

Exclusion Criteria:

1. Meets current criteria for a manic episode, rapid cycling within the past year (history of 4 or more mood episodes per year)
2. History of schizophrenia or other nonaffective psychosis
3. Current substance use disorder that will interfere with participation in the study
4. Currently taking the study medications or a history of serious adverse events to any of the study medications, to the extent that as determined by site PI, another trial would not be clinically indicated
5. A history of non-response for depressive episodes, to any of the study medications, when given at adequate doses for at least 6 weeks
6. Current acute suicidal risk that requires inpatient treatment
7. Pregnancy or breastfeeding

Where this trial is running

Birmingham, Alabama and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Bipolar I DisorderDepressionBipolarAdultsMedication
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.