Sequential Multiple Assignment Randomized Trial for Bipolar Depression

Study on Treatments for Bipolar Depression

S
Steve Strakowski

Primary Investigator

Enrolling By Invitation
18 years - 75 years
All
Phase N/A
147 participants needed

Brief description of study

This is a sequential multiple assignment randomized trial for adults (ages > 18) with a bipolar disorder type 1 diagnosis currently experiencing a depressive episode. It is a randomized pragmatic trial that will compare four commonly prescribed treatments for bipolar depression, which includes three FDA-approved medications (Cariprazine, Quetiapine and Lurasidone) and one antipsychotic/antidepressant combination (Aripiprazole/Escitalopram).
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - IU-affiliated investigators will identify subjects with bipolar depression and randomize them to one of four treatment options.

Detailed description of study

 

This is a comparative effectiveness study to address the critical questions of how best to treat people with bipolar disorder who have a major depressive episode: how to get them well, provide second-line treatment when they don't initially get well, and keep them well after they get well. 

  • This is a multisite Sequential Multiple Assignment Randomized Trial (SMART) comparative effectiveness design.
  • Investigators will recruit 2726 participants who have BD with a current major depressive episode.
  • In Stage 1, investigators will compare four treatment arms, including three FDA approved monotherapies and the most widely used, but understudied, treatment for BD major depressive episode (i.e., a non-FDA approved combination of an antipsychotic and antidepressant).
  • In Stage 2, participants who do not remit will be re-randomized to treatments not used in Stage 1.
  • Investigators will follow all participants for a total of 52 weeks.
  • This study will be conducted in two phases, a feasibility phase and a full study phase.
  • In the feasibility phase, investigators will recruit at 8 of the 19 study sites based on readiness and interest, to ensure the efficacy of the study design before launching the full study phase.
  • Investigators will assess the efficacy of the treatments throughout the study visits. Participants whose depression does not remit in 6 weeks will be reassigned to another available treatment. The investigator will continue to assess the participant's depressive symptoms following the medication change. Participants will be followed for 52 weeks.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Bipolar I Disorder, Depression
  • Age: 18 years - 75 years
  • Gender: All

Inclusion Criteria:

  1. Aged between 18 years to 75 years
  2. Meets criteria for DSM-V Bipolar I or II disorder with a history of manic or hypomanic episodes and current major depressive episode lasting at least 2 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

This study investigates treatment options for people with bipolar disorder who are currently experiencing a depressive episode. Bipolar disorder is a mental health condition that causes extreme mood swings, including emotional highs (mania or hypomania) and lows (depression). The purpose of this study is to compare four different treatment arms, including three approved medications and one combination treatment, to find the best way to manage depression in individuals with bipolar disorder.

Participants in the study will be randomly assigned to one of four treatment arms. If a participant's depression does not improve after six weeks, they will be reassigned to a different treatment. The study involves regular assessments of depressive symptoms and will last for a total of 52 weeks. Investigators will monitor the effectiveness of the treatments throughout the study.

  • Who can participate: Adults aged 18 to 75 years with Bipolar I or II disorder and a current major depressive episode lasting at least 2 weeks can participate. They must manage as outpatients and agree to randomization.
  • Study details: Participants will be randomly assigned to one of four treatment arms. If the initial treatment does not improve their symptoms, they will be reassigned to a different treatment.
  • Study timelines: The study will last 52 weeks.
Updated on 30 Apr 2026. Study ID: PSYC-MGB-SMART-BD, 23677
Please visit our main page to search for other studies you may be interested in. If you need help finding a study or have any questions, please contact us at inhealth@iu.edu

Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only