Biosignatures of Latuda for Bipolar Depression

The study proposes to enroll 20 participants with a bipolar disorder who are currently in an
episode of major depression.Magnetic resonance imaging (MRI), recordings of brain electrical
activity (EEG), and psychological testing to explore possible predictors of lurasidone
treatment response will be conducted. Blood samples will be collected for a future study of
blood protein predictors of response. After testing, participants will receive an open-label
8-week trial of lurasidone (Latuda™) at approved dosage levels. Participants who attain
remission of their major depressive episode will be eligible for a six-month continuation
phase to explore predictors of sustained response to continuation treatment. Data analyses
will use statistical testing to explore potential biological predictors of lurasidone
response. This will provide a framework for clarifying which patients are best suited to this
treatment and begin to develop a model for precision treatment of this difficult-to-treat
disorder.

Inclusion Criteria:

1. Age 18- 60

2. Outpatients with a primary Diagnostic and Statistical Manual of the American
Psychiatric Association, Fourth Edition (DSM-IV) diagnosis of Bipolar Disorder I, II,
or NOS (Not Otherwise Specified)

3. Current episode of Major Depression

4. At least moderate severity of depression

5. Agrees to, and is eligible for, electroencephalogram (EEG) / psychological testing,
magnetic resonance imaging (MRI), and blood draws

6. Provides informed consent

Exclusion Criteria:

1. Current drug or alcohol abuse/dependence, except nicotine (within 6 months for
dependence; 2 for abuse)

2. Taking any of the following exclusionary medications: antipsychotics, anticonvulsants,
mood stabilizers, stimulants, antidepressant medications, medications with significant
interactions with lurasidone, except during the washout prior to testing and blood
collection

3. Unstable medical condition, including significant liver disease, hypothyroidism (i.e.,
condition not adequately stabilized for 3 months), and conditions likely to require
hospitalization or with a life expectancy of < 6 mos.*

4. Patients considered at significant risk for suicide

5. Inadequate understanding of English

6. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive
methods; plan to become pregnant within 12 months

7. Contraindications to MRI (e.g. ferromagnetic body implants, history of metal working,
etc.)

8. Have epilepsy, neuromuscular disorder, or tardive dyskinesia

9. Require immediate hospitalization for psychiatric disorder

10. Require medications for a general medical condition that contraindicate any study
medication**

11. Receiving or have received during the index episode vagus nerve stimulation,
electroconvulsive therapy, transcranial magnetic stimulation, or other somatic
treatments

12. Allergy to, or other medical contraindication to lurasidone treatment

13. Currently enrolled in another research study, and participation in that study
contraindicates participation

14. Clinically significant screening laboratory abnormalities (* see below)

15. Currently taking an effective mood stabilizer and/or antidepressant regimen

16. Inability to undergo a three week medication-free period, including history of
significant clinical deterioration from past periods off medication or when medication
dosage was reduced, including mania, severe depression, etc.

17. Any reason not listed herein that would make participation in the study hazardous
*Medical criteria for exclusion:

- Untreated hypertension: > 140/90 Torr on repeated measurement (If hypertension
becomes stabilized, subject may enroll in study)

- Hepatitis: any liver function test > 2x the upper limit of normal

- Renal failure: estimated Glomerular Filtration Rate (eGFR, corrected for body
surface area) repeatedly < 30 mL/min

- Hypothyroidism: thryrotropin stimulating hormone level > upper limit of normal
(unless accompanied by other euthyroid indices and the confirmation by an
internist or endocrinologist that this does not represent hypothyroidism)

- Anemia: hemoglobin < 10 grams/deciliter (borderline hemoglobin must be of known
origin, stable, and not clinically significant)