Combinatorial Pharmacogenomics Testing in Treatment-Naïve Major Depressive Disorder

Major Depressive Disorder is a chronic psychiatric illness that leads to devastating
consequences at the individual and societal levels. Today, the choice of treatment continues
to be largely based on subjective factors, primarily the clinician and/or patient's
preferences, as well as the individual's history of response to treatment, often tainted by
recall bias. Psychiatric medication decisions are even more arbitrary when the subject in
question has not had past treatment trials. This often leads to a trial and error process and
an increasingly resistant disease with each failed trial. Early implementation of an
objective tool designed for tailoring medication choice to an individual may prove highly
beneficial in decreasing illness chronicity, individual suffering, and economic burden.

GeneSight Psychotropic test is a pharmacogenomic decision support tool, developed to help
clinicians make informed, evidence-based decisions about proper drug selection. Therefore, we
propose conducting a randomized, double blind, controlled trial to evaluate the impact of the
GeneSight Psychotropic test to guide treatment decisions in patients with treatment-naïve
(never having taken medication for depression) Major Depressive Disorder.

This study will involve 6 visits over about 24 weeks where participants will be randomized to
have their study clinician have access to their pharmacogenetic report in order to make
treatment decisions, or to not have access to their report for the first 12 weeks. At Visit
5, Week 12, all participants will receive a copy of their pharmacogenetics report and all
clinicians will be unblinded to be able to use the results to guide treatment options for an
additional 12 weeks.

Inclusion Criteria:

1. Adults 18-65 years of age

2. Treatment-naïve major depressive disorder meeting Diagnostic and Statistical Manual
4th Edition (DSM-IV) criteria, without psychosis

3. Total baseline score on the Quick Inventory Of Depressive Symptomatology
Clinician-rated (QIDS-C16) and the Quick Inventory Of Depressive Symptomatology
Self-Report (QIDS-SR16) rating scale ≥11

4. Good command of the English language

Exclusion Criteria:

1. Patients with a current diagnosis of schizophrenia

2. Patients with a current diagnosis of schizoaffective disorder

3. Patients with a current diagnosis of bipolar disorder (any type)

4. Currently meeting DSM-IV criteria for significant substance use disorder (exception:
nicotine use disorder)

5. A diagnosis of personality disorder that may interfere with the patient's ability to
improve on pharmacologic treatment, as determined by study investigator

6. Patients currently receiving electroconvulsive therapy(ECT), deep brain stimulation
(DBS) or transcranial magnetic stimulation (TMS) treatment

7. History of hypothyroidism unless taking a stable dose of thyroid medication and
asymptomatic or euthyroid for 6 months

8. Significant unstable medical condition; life threatening disease; hepatic
insufficiency; liver transplant recipient; cirrhosis of the liver; need for therapies
that may obscure the results of treatment and/or of the study; malignancy (except
basal cell carcinoma) and/or chemotherapy within 1 year prior to screening; malignancy
more than 1 year prior to screening must have been local and without metastasis and/or
recurrence, and if treated with chemotherapy, without nervous system complications

9. History of gastric bypass surgery

10. Acute suicidal intention and/or in need of immediate hospitalization as judged by the
investigator

11. Active psychotic symptoms

12. Currently in an inpatient facility

13. History of prior pharmacogenomic testing

14. Currently pregnant or lactating

15. Inability to provide informed consent

16. Any other factor that in the investigators' judgment may affect patient safety or
compliance