Multiple Medications for Bipolar Depression

(SMART-BD Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests four treatments for bipolar depression to determine which is most effective during a depressive episode. The treatments include three FDA-approved medications—Cariprazine, Quetiapine, and Lurasidone (all antipsychotics)—and a combination of Aripiprazole and Escitalopram (an antipsychotic and an antidepressant). It is open to adults with bipolar disorder type 1 who have experienced a depressive episode for at least six weeks and can participate as outpatients. Participants should not currently have manic episodes or substance use issues that would interfere with the study. As a Phase 4 trial, this research aims to understand how these FDA-approved treatments benefit more patients.

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 is the safety track record for these treatments?

Research has shown that the treatments in this trial have been generally safe and well-tolerated in past studies. Here is a closer look at each one:

1. **Cariprazine**: Previous studies found cariprazine to be generally safe. Common side effects include nausea, restlessness, and movement-related issues such as a feeling of inner restlessness (akathisia) and movement disorders (extrapyramidal symptoms). These effects occurred in more than 5% of patients but are usually mild.

2. **Aripiprazole/Escitalopram combination**: Studies on aripiprazole and escitalopram separately have shown they are well-tolerated. Aripiprazole, when used as an additional treatment, has a good long-term safety record. Both medicines are also FDA-approved for other conditions, indicating a reasonable safety history.

3. **Lurasidone**: Research has found lurasidone to be generally safe for long-term use, even up to two years. It has a low rate of side effects and is effective for treating bipolar depression.

4. **Quetiapine**: This medication is used for bipolar depression and is typically safe. However, it can cause side effects like dizziness, sleepiness, and dry mouth, but these are usually manageable.

In summary, all these treatments have been tested before and are generally considered safe, with some mild side effects that are common but manageable. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for bipolar depression because they offer unique approaches compared to standard options like lithium, valproate, or olanzapine. The Aripiprazole/Escitalopram combination may provide the dual benefit of mood stabilization and enhanced antidepressant effects, potentially improving overall symptom management. Cariprazine stands out for its selective action on dopamine receptors, which might offer better control of depressive symptoms with fewer side effects. Lurasidone is appreciated for its favorable side effect profile, particularly regarding weight gain and metabolic issues, which are common concerns with other treatments. Quetiapine is noted for its rapid onset of action, which could bring quicker relief to patients in acute depressive episodes. Each of these treatments brings something new to the table, offering hope for more personalized and effective management of bipolar depression.

What evidence suggests that this trial's treatments could be effective for bipolar depression?

In this trial, participants will join one of several treatment arms to evaluate different medications for bipolar depression. Cariprazine, one of the treatments under study, has significantly reduced depressive symptoms and improved overall functioning in people with bipolar I disorder, according to previous research. Lurasidone, another treatment option in this trial, effectively reduces depression and anxiety, with improvements often seen as early as two weeks into treatment. Quetiapine, also being tested, has improved depressive symptoms and overall quality of life for those with bipolar disorder. Additionally, the combination of aripiprazole and escitalopram, which participants may receive, may enhance quality of life and thinking skills, although aripiprazole alone works better for manic episodes rather than depressive ones. Research strongly supports these treatments for improving depressive episodes in bipolar disorder. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33860922/

Predictors of Quality of Life Improvement with Escitalopram ... Results: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06433635?term=New%20York%20University%20Grossman%20School%20of%20Medicine&viewType=Table&rank=7

Study Details | NCT06433635 | Sequential Multiple ... Aripiprazole monotherapy in bipolar I patients reduced relapse rates and delayed relapse time, but not for depressive episodes. Aripiprazole acts as a partial ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032723012284

Effect of aripiprazole on promoting cognitive function and ... Escitalopram combined with a low-dose of aripiprazole, and escitalopram monotherapy could both enhance cognitive function of MDD patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4859817/

The Treatment of Adult Bipolar Disorder with Aripiprazole Aripiprazole is found to be efficacious in the treatment and prophylaxis of manic and mixed episodes but has no effectiveness in acute and recurrent bipolar ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0028390818305768

Synergistic effect of aripiprazole and escitalopram in ... This study investigated how aripiprazole, escitalopram and their combination affect the net effect of 5-HT and NE neurotransmission in the rat hippocampus.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3104689/

Long-term safety and tolerability of open-label aripiprazole ... Overall, aripiprazole augmentation was well tolerated, with an acceptable long-term safety and tolerability profile in patients with major depressive disorder ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2626914/

Augmentation treatment in major depressive disorder Based on these efficacy and safety data, aripiprazole was recently approved by the FDA as adjunctive therapy for MDD. The availability of this new treatment ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01111552

NCT01111552 | Study to Evaluate the Efficacy, Safety and ... This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram ...

9. trial.medpath.com trial.medpath.com/clinical-trial/f982aa6e974bdcc3/nct01123707-multicenter-open-label-study-aripiprazole-escitalopram

To Assess the Safety and Tolerability of an Oral Aripiprazole ... This is a multicenter, 52-week, open-label study designed to assess the safety and tolerability of an oral aripiprazole/escitalopram combination ...