Research

Sequential Multiple Assignment Randomized Trial for the Treatment of Bipolar Depression

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Project Summary

This study compares the clinical effectiveness of four treatments for bipolar depression: three Food and Drug Administration approved medications for the treatment of bipolar depression (cariprazine, lurasidone and quetiapine) and a commonly used antipsychotic and antidepressant combination (aripiprazole and escitalopram).

Who will this research inform?

Over 90% of people with bipolar disorder experience multiple mood episodes over their lifetime, and depressive episodes are associated with poorer functioning and a substantially increased risk of suicidal thoughts, suicidal behavior and death by suicide. Even though it is a top 10 cause of global disability, little is known about the comparative effectiveness of treatments for bipolar depressive episodes. Results from this study will provide patients, clinicians and payers with information on which agent to choose first or what to use next if the first agent does not help.

What is the research team doing?

DesignSequential Multiple Assignment Randomized Trial (SMART)
Population2,726 adults ages 18-75 with bipolar Type 1, who are currently experiencing a major depressive episode
Interventions/
Comparators
  • Cariprazine
  • Lurasidone
  • Quetiapine
  • Aripiprazole and escitalopram

Treatments consist of an initial acute treatment period of up to 12 weeks. Participants who do not respond to treatment after the initial 6 weeks will be re-randomized into a different therapy arm for the next 6 weeks. All participants will be followed for up to 52 weeks.

Primary OutcomeRemission of depression at weeks 6 and 12
Secondary OutcomesSide effects and safety of treatment
Patient and Community EngagementPeople with bipolar depression, clinicians and payers are working with the research team on this study.

Project Information

Andrew Nierenberg, MD
Andrea Foulkes, PhD
Massachusetts General Hospital
$2,570,590

Key Dates

July 2022
May 2026

Study Registration Information

NCT06433635

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Last updated: August 11, 2026