Escitalopram + Brexpiprazole for Depression

(CAN-BIND-17 Trial)

Recruiting at 4 trial locations

Overseen By Roumen Milev, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University Health Network, Toronto

Must not be taking: Antidepressants, Psychotropics

Disqualifiers: Bipolar, Substance abuse, Neurological disorders, others

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

Compensation: Varies

Number of Visits: 7

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the combined effectiveness of escitalopram and brexpiprazole (an antipsychotic medication) in treating major depressive episodes (MDE). Researchers will use a special algorithm to predict patient responses based on various data, such as clinical and imaging results. Participants will be divided into groups to receive different combinations of these medications, with some receiving a placebo (a substance with no active drug) for comparison. This trial suits individuals who have experienced major depression, are not currently on psychotropic medications, and can communicate in English. As a Phase 4 trial, the research focuses on understanding how these FDA-approved and effective treatments can benefit more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking psychotropic medications (drugs that affect your mood, thoughts, or behavior) for at least 5 half-lives before the study starts, which is about 1 week for most antidepressants and 5 weeks for fluoxetine. However, you can continue using stable doses of sleep aids or ADHD medications.

What is the safety track record for Brexpiprazole and Escitalopram?

Research shows that combining escitalopram and brexpiprazole is generally well-tolerated by people with major depressive disorder. Studies have found that adding brexpiprazole to an antidepressant like escitalopram can help reduce depression symptoms and improve social interactions. However, some side effects, such as weight gain and restlessness, have been reported with brexpiprazole. Despite this, doctors often consider the treatment safe for many patients when monitored.

This trial is a Phase 4 study, focusing on treatments already approved and commonly used. This indicates a strong safety record, as these treatments have been tested in many people. Always consult a healthcare provider about potential side effects and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining escitalopram with brexpiprazole for treating depression because this approach targets the condition in a unique way. Escitalopram is a well-known antidepressant that works by increasing serotonin levels in the brain. Brexpiprazole, on the other hand, is an antipsychotic that can help enhance the effects of escitalopram by acting on different neurotransmitter systems, potentially offering a more comprehensive treatment. This combination could be more effective for patients who don't respond well to traditional antidepressants alone, offering hope for improved outcomes in managing depression.

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

Research has shown that adding brexpiprazole to antidepressants like escitalopram can reduce symptoms of major depression, especially when other treatments have failed. In this trial, some participants will receive a combination of escitalopram and brexpiprazole, while others will receive escitalopram with a placebo. Studies have found that brexpiprazole, when used with antidepressants, can improve mood and social interactions. Patients have experienced benefits from taking up to 2 mg of brexpiprazole daily for as little as six weeks. It is also considered safe for long-term use, up to a year, although some people might feel dizzy. This combination is regarded as a strong option for treating difficult cases of depression. ^{1 2 3 4 6}

Who Is on the Research Team?

Rudolf Uher, MD

Principal Investigator

Nova Scotia Health Authority

Are You a Good Fit for This Trial?

The OPTIMUM-D trial is for adults aged 18-60 with major depressive disorder (MDD) and a current major depressive episode (MDE). Participants must have a moderate to severe depression score, no significant mental or physical health issues, not be on psychotropic meds recently, speak English fluently, and have had the episode for at least 3 months. Excluded are those with bipolar disorder, unstable conditions, pregnancy/breastfeeding women, multiple failed depression treatments, recent psychotherapy starters or intolerance to study drugs.

Inclusion Criteria

Are you currently depressed?

In the past two weeks, have you been feeling down, depressed, or hopeless most days?

Would you be able to pass a urine drug screen as a regular part of the study?

Exclusion Criteria

In the last year, have you taken any antipsychotic medication?

In the past 6 months, have you had thoughts that you would be better off dead or considered harming yourself?

In the last 6 months, have you struggled with substance use (including alcohol, nicotine, marijuana, or other recreational drugs)?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Treatment

Participants receive open-label escitalopram and either blinded placebo or brexpiprazole based on group assignment for 8 weeks

8 weeks

4 visits (in-person)

Secondary Extension

Participants continue treatment with open-label escitalopram and either open-label brexpiprazole or no additional medication based on response for 4 weeks

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brexpiprazole
• Escitalopram

Trial Overview This trial tests whether data from clinical assessments, brain scans (imaging), EEGs (brain wave tests), and molecular studies can predict how well patients will respond to two antidepressants: Escitalopram or Brexpiprazole. It's conducted across eight sites using an algorithm developed from previous research.

How Is the Trial Designed?

Group I: Random Allocation; Escitalopram + Brexpiprazole Active Control 2 Interventions

Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.

Group II: Allocation by Predictive Biomarker Algorithm; Escitalopram + Brexpiprazole Active Control 2 Interventions

Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted as non-responders to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded brexpiprazole (0.5-2 mg/d) for the first 8 weeks of the study. For the final 4 weeks of the study, patients will continue to receive both medications but the brexpiprazole will no longer be blinded.

Group III: Allocation by Predictive Biomarker Algorithm; Placebo Placebo Group 1 Intervention

Patients are randomly assigned to the Allocation by Predictive Biomarker Algorithm group. Based on the outcome result from the personalized predictive biomarker algorithm, patients predicted to respond to escitalopram monotherapy will receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.

Group IV: Random Allocation; Placebo Placebo Group 1 Intervention

Patients are randomly assigned to the Random Allocation group and then randomly assigned to receive open-label escitalopram (10-20 mg/d) and blinded placebo for the first 8 weeks of the study. For the final 4 weeks of the study, responders will continue to receive open-label escitalopram without the placebo and non-responders will receive a combination of open-label escitalopram and open-label brexpiprazole.

Brexpiprazole is already approved in United States, Canada, European Union, Japan, Brazil for the following indications:

Approved in United States as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia
• Agitation associated with dementia due to Alzheimer's disease

Approved in Canada as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)
• Schizophrenia

Approved in European Union as Rexulti for:

• Schizophrenia

Approved in Japan as Rexulti for:

• Schizophrenia

Approved in Brazil as Rexulti for:

• Major depressive disorder (as an adjunctive therapy to antidepressants)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Nova Scotia Health Authority

Lead Sponsor

Trials

302

Recruited

95,300+

Queen's University

Collaborator

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Baycrest

Collaborator

Trials

46

Recruited

6,900+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Simon Fraser University

Collaborator

Trials

59

Recruited

12,500+

Centre for Addiction and Mental Health

Collaborator

Trials

388

Recruited

84,200+

McGill University

Collaborator

Trials

421

Recruited

1,017,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6872963/

Brexpiprazole as Adjunctive Treatment for Major ... Conclusions. Brexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X17300470

The novel antipsychotic drug brexpiprazole, alone and in ... At lower doses, add-on treatment with brexpiprazole to antidepressant drugs (ADs) reduced depressive symptoms and improved social functioning in treatment- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11878111/

Preclinical Evidence for the Use of Brexpiprazole + ... Based on a small number of studies, the administration of brexpiprazole with an antidepressant appears to have a greater treatment effect than either ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1555415525001412

Major Depressive Disorder and Difficult-to-Treat ... Aripiprazole and brexpiprazole show strong efficacy in difficult-to-treat depression. •. Adjunctive therapy should be considered early during partial ...

5. withpower.com withpower.com/trial/phase-4-depressive-disorder-major-8-2021-b574a

Escitalopram + Brexpiprazole for Depression One study found that brexpiprazole, when combined with other antidepressants, was safe for up to 52 weeks. However, possible side effects include dizziness, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03538691

NCT03538691 | A Trial to Evaluate the Efficacy, Safety & ... A Trial to Evaluate the Efficacy, Safety & Tolerability of Brexpiprazole in the Maintenance Treatment of Adults With Major Depressive Disorder. ClinicalTrials.