Recruiting
Phase 3

Brexpiprazole

Sponsor:

Douglas Mental Health University Institute

Code:

NCT04569448

Conditions

Bipolar Depression

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Brexpiprazole

Study Details

Brief summary:

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.

Conditions

Bipolar Depression

Study ID

NCT04569448

Start date

May 10, 2021

Status verified date

Aug, 2026

Completion date

Dec, 2030

Anticipated

Primary completion date

Sep, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

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

Study Design

Enrollment

58 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Patient

Individuals diagnosed with Bipolar Disorder Type I or Type II and suffering a major depressive episode who will receive an adjunctive and variable dose of Brexpiprazole treatment

Interventions

Brexpiprazole

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

Primary outcome measure

  • Change from Baseline Depressive Symptoms as Assessed by MADRS at 8 weeks [ Time Frame: 8 weeks ]

Central Contacts and Locations

Central contacts

Gabrielle Phillips, BA

514 444 5397gabrielle.phillips.comtl@ssss.gouv.qc.ca

Paola Lavin Gonzalez, MD, MSc

438 389 8181maria.lavingonzalez@mail.mcgill.ca

Locations

Douglas Mental Health University Institute

Recruiting

Montreal, Quebec, Canada, H4H 1R3

Contacts

Lori Moreno, BSc

514 444 5397lori.moreno.comtl@ssss.gouv.qc.ca

Principal Investigator:

Serge Beaulieu, MD, PhD, FRCPC, DFAPA

More Information

Sponsor

Douglas Mental Health University Institute

Last update posted

Aug 27, 2026

Last verified

Aug, 2026

Keywords

  • Brexpiprazole
  • Treatment-resistant depression
  • Cognition
  • Functioning
  • Rest-Activity rhythm
  • Hippocampus
  • CRP

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Douglas Mental Health University Institute on 2026-08-27.