Brexpiprazole Treatment for Bipolar I Depression

Low-Dose Adjunctive Brexpiprazole in the Treatment of Bipolar I Depression: An Open-Label Study

Brexpiprazole Treatment for Bipolar I Depression (NCT04569448) is a Phase 3 interventional studying Bipolar Depression, sponsored by Douglas Mental Health University Institute. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I and type II depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Bipolar Depression, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 58 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Bipolar Depression subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Patient Who May Qualify: - Age: 18-75 - Male or female - Bipolar Disorder type I or type II - Current treatment-resistant depressive episode (with MADRS \>/= 24 and item 2 (reported sadness) \>/= 3) for a minimum of 2 weeks but \</= 52 weeks at screening visit and baseline visit - Patients must have failed at least one other treatment for the current depressive episode - If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation - Is treated with a mood stabilizer (lithium and/or valproate and/or lamotrigine and/or quetiapine \</= 100mg/day) - The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin - Normal EKG at Screening - Patient is able to give his(her) consent Patient Who Should NOT Join This Trial: - Is at high risk of suicide as defined by a score of \>/= 3 to item 10 of MADRS and/or in the clinical opinion of the investigator - Hypo(mania) episode with YMRS \>/= 8 - Psychotic symptoms as defined by a score of \>/= 4 to item 8 (content) of YMRS and/or in the opinion of the investigator - Is treated with fluoxetine OR carbamazepine - Is treated with risperidone OR olanzapine OR quetiapine \> 100mg/day OR ziprazidone OR any other antipsychotic - Is pregnant or lactating or absence of contraceptive treatment - Drug abuse or dependence as per DSM-V (MINI) - Unstable medical condition - Other unstable and/or untreated psychiatric condition, organic brain disorder, unstable and/or untreated medical condition such as hypothyroidism, hyperthyroidism, diabetes, cardiac condition, hypertension - Deficit in vitamin B12 or folate ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Patient Inclusion Criteria: * Age: 18-75 * Male or female * Bipolar Disorder type I or type II * Current treatment-resistant depressive episode (with MADRS \>/= 24 and item 2 (reported sadness) \>/= 3) for a minimum of 2 weeks but \</= 52 weeks at screening visit and baseline visit * Patients must have failed at least one other treatment for the current depressive episode * If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation * Is treated with a mood stabilizer (lithium and/or valproate and/or lamotrigine and/or quetiapine \</= 100mg/day) * The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin * Normal EKG at Screening * Patient is able to give his(her) consent Patient Exclusion Criteria: * Is at high risk of suicide as defined by a score of \>/= 3 to item 10 of MADRS and/or in the clinical opinion of the investigator * Hypo(mania) episode with YMRS \>/= 8 * Psychotic symptoms as defined by a score of \>/= 4 to item 8 (content) of YMRS and/or in the opinion of the investigator * Is treated with fluoxetine OR carbamazepine * Is treated with risperidone OR olanzapine OR quetiapine \> 100mg/day OR ziprazidone OR any other antipsychotic * Is pregnant or lactating or absence of contraceptive treatment * Drug abuse or dependence as per DSM-V (MINI) * Unstable medical condition * Other unstable and/or untreated psychiatric condition, organic brain disorder, unstable and/or untreated medical condition such as hypothyroidism, hyperthyroidism, diabetes, cardiac condition, hypertension * Deficit in vitamin B12 or folate * Rapid cycling (more than 4 mood episodes per year) * Active or history of difficulty to swallow * Seizures not currently controlled with medications * Orthostatic hypotension defined as a drop in systolic blood pressure of at least 20 mmHg or of diastolic BP of at least 10 mmHg within 3 minutes of standing * A history of clinically significant cardiovascular disorders and cardiac arrhythmias * A low white blood cell count * Known eye disease * Involuntary, irregular muscle movements, especially in the face * Known hypersensitivity to Brexpiprazole and any components of its formulation * Known lactose intolerance or have hereditary galactose intolerance or glucose-galactose malabsorption, because Brexpiprazole and placebo tablets contain lactose (a disaccharide of glucose and galactose) * Active inflammatory disease including lupus, colitis, Crohn's disease, psoriasis, irritable bowel syndrome (IBS) * Mild or major neurocognitive disorder * Previous history of sensitivity/low tolerance to medications metabolized by CYP 2D6 inhibitors, or CYP 3A4 inducers Control Inclusion Criteria: * Age: 18-75 * Male or female * No current or past history of any psychiatric disorder * Patients must have failed at least one other treatment for the current depressive episode * If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation * The following laboratory values are within normal limits at Screening: CBC with differential; ferritin; extended electrolytes (sodium, potassium, chloride, calcium, magnesium, phosphate); thyroid function test(s); kidney function tests; hemoglobin A1c; lipid profile; prolactin * Normal EKG at Screening * Patient is able to give his(her) consent Control Exclusion Criteria: * Alcohol or drug abuse * Deficit in vitamin B12 or folate * Seizures not currently controlled with medications * History of clinically significant cardiovascular disorders and cardiac arrhythmias * Mild or major neurocognitive disorder Patient/Control Exclusion Criteria for MRI: * Pacemaker * Heart/vascular clip * Metal prosthesis * Metal fragments in body * Transdermal patch * Aneurysm clip * Prosthetic valve * Claustrophobia * Pregnant

Treatments Being Tested

DRUG

Brexpiprazole

Adjunctive variable dose (1-3 mg/day) Brexpiprazole

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

McMaster University

Hamilton, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Douglas Mental Health University Institute

Montreal, Quebec, Canada

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04569448), the sponsor (Douglas Mental Health University Institute), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04569448 clinical trial studying?

Who can participate in NCT04569448?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04569448?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04569448. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04569448. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.