Brexpiprazole Treatment for Bipolar I Depression

Participation Requirements

• Sex:

  ALL

• Eligible Ages:

  18 to 75

Participation Criteria

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