Multiple Medications for Bipolar Depression

(SMART-BD Trial)

Recruiting at 17 trial locations

Overseen By Dost Ongur

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Massachusetts General Hospital

Must not be taking: Study medications

Disqualifiers: Manic episode, Schizophrenia, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

2726 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing four different medications to find the best treatment for adults with bipolar disorder type 1 who are currently depressed. The medications work by balancing brain chemicals that affect mood. The goal is to help patients recover from depression and stay well.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop your current medications. However, if you are currently taking any of the study medications, you may not be eligible to participate.

What data supports the effectiveness of the drug combination Aripiprazole/Escitalopram for treating bipolar depression?

Quetiapine and lurasidone, which are part of the same class of drugs as aripiprazole, have been shown to be effective for treating bipolar depression. However, there is no direct evidence supporting the effectiveness of the Aripiprazole/Escitalopram combination specifically for bipolar depression. ^{1 2 3 4 5}

Is the Aripiprazole/Escitalopram combination, Cariprazine, or Quetiapine safe for humans?

Cariprazine has been studied for safety in treating conditions like schizophrenia and bipolar disorder. It is generally considered safe, but some people may experience side effects like movement disorders (extrapyramidal symptoms) and stomach issues. Always consult with a healthcare provider for personalized advice. ^{6 7 8 9 10}

How is the Aripiprazole/Escitalopram combination, Cariprazine, Lurasidone, and Quetiapine drug treatment for bipolar depression different from other drugs?

This treatment is unique because it combines multiple medications, including Aripiprazole, which has a distinct mechanism of action as a partial agonist at dopamine and serotonin receptors, and Cariprazine, which also targets dopamine and serotonin receptors. These drugs are known for their efficacy in treating different phases of bipolar disorder, and the combination aims to address both depressive and manic symptoms, potentially offering a broader spectrum of relief compared to single-drug therapies. ^{1 5 11 12 13}

Eligibility Criteria

Adults over 18 with bipolar disorder type 1 who are currently in a depressive episode can join this trial. It's not specified, but typically participants need to meet certain health criteria and may be excluded for various reasons such as other medical conditions or treatments that could interfere with the study.

Inclusion Criteria

Can be managed as an outpatient and participate in the study

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.

I have been diagnosed with Bipolar I disorder and am currently experiencing a major depressive episode that has lasted for at least 6 weeks.

Exclusion Criteria

Current substance use disorder that will interfere with participation in the study

Pregnancy or breastfeeding

History of schizophrenia or other nonaffective psychosis

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Feasibility Phase

Recruitment, randomization, and retention of participants at selected sites to ensure study design efficacy

6 weeks

Baseline and 6-week visits

Stage 1 Treatment

Participants receive one of four treatment arms for bipolar depression

6 weeks

Visits every 2 weeks

Stage 2 Treatment

Non-remitters from Stage 1 are re-randomized to different treatments

6 weeks

Visits every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 weeks

Visits at weeks 20, 28, 36, 44, and 52

Treatment Details

Interventions

• Aripiprazole/Escitalopram combination
• Cariprazine
• Lurasidone
• Quetiapine

Trial Overview The trial is testing four treatments for bipolar depression: Cariprazine, Quetiapine, Lurasidone (all FDA-approved), and an Aripiprazole/Escitalopram combo. Patients will be randomly assigned to one of these treatments in sequence to see which works best.

Participant Groups

Group I: Quetiapine Experimental Treatment 1 Intervention

Group II: Lurasidone Experimental Treatment 1 Intervention

Group III: Cariprazine Experimental Treatment 1 Intervention

Group IV: Aripiprazole /Escitalopram combination Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Findings from Research

Cariprazine is a novel antipsychotic medication that has shown efficacy in treating acute psychosis in schizophrenia and mania in bipolar disorder, making it a promising option for these conditions.

While cariprazine has been approved by the FDA, it can cause side effects such as extrapyramidal symptoms and gastrointestinal issues, which are important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on schizophrenia and bipolar disorder: focus on cariprazine. Roberts, RJ., Findlay, LJ., El-Mallakh, PL., et al.[2020]

In a phase 3 study involving 493 adults with bipolar I disorder, cariprazine at a dose of 1.5 mg/day significantly reduced depressive symptoms compared to placebo, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

The 3.0 mg/day dose did not show significant benefits over placebo, and the safety profile was consistent with previous studies, with common side effects including akathisia and nausea, but minimal weight gain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. Earley, WR., Burgess, MV., Khan, B., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Evidence of treatment for depressive episodes of bipolar disorder]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Monotherapy versus combined treatment with second-generation antipsychotics in bipolar disorder. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Second generation antipsychotics in the treatment of bipolar depression: a systematic review and meta-analysis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Bipolar depression: Managing patients with second generation antipsychotics. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Pros and cons of approved therapies for bipolar depression and ongoing unmet needs. [2015]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Mini Review on Cariprazine: A Promising Antipsychotic Agent. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Update on schizophrenia and bipolar disorder: focus on cariprazine. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Cariprazine as a treatment across the bipolar I spectrum from depression to mania: mechanism of action and review of clinical data. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The safety and tolerability of cariprazine in patients with manic or mixed episodes associated with bipolar I disorder: A 16-week open-label study. [2018]

10. Denmark pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cariprazine in bipolar I depression: A double-blind, placebo-controlled phase 3 study. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

When to start aripiprazole therapy in patients with bipolar mania. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

A pooled post hoc analysis evaluating the safety and tolerability of cariprazine in bipolar depression. [2021]

13. Denmark pubmed.ncbi.nlm.nih.gov

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2009. [2022]