A Pharmacokinetic/Pharmacodynamic Genetic Variation Treatment Algorithm Versus Treatment As Usual for Management Of Depression

Treatment seeking depressed patients (SCID confirmed major depressive disorder or bipolar
I/II disorder) to the Mayo Clinic Depression Center will be invited to participate in this
study evaluating the Assurex GeneSight® platform; this new technology can rapidly assess PK
and PD genetic variation that can potentially impact antidepressant, antipsychotic, and
stimulant associated treatment outcomes for depression. This study will recruit treatment
seeking patients with major depression with an index episode of moderate symptom severity
that has been unresponsive or poorly tolerated to at least one prior antidepressant
treatment. This will be an 8-week, double-blind trial where depressed patients are randomized
to testing results of GeneSight® (tricolored clinical report) prior to treatment selection
(n=138) vs. treatment as usual (tricolored dummy report) (n=138). All testing results will be
made available after the 8-week trial.

Inclusion Criteria:

1. Age 18-65, male or female, any race/ethnicity

2. Mayo Clinic Depression Center inpatient or outpatient, or an outpatient of Mayo Clinic
Rochester and satellite clinics, and outpatients from Mayo Clinic Health System
clinics

3. Ability to provide informed consent

4. Structured Clinical Interview (SCID) confirmed major depressive episode associated
with Major Depressive Disorder, Bipolar I/II disorder, or Schizoaffective Bipolar
Disorder

5. Current index episode of major depression < 2 years duration

6. Moderate symptom severity defined by HAMD-17 rating scale score ≥ 17 [8]

7. Current index episode having not been treated with psychotropic medications or
inadequately responsive to treatment (IRT). IRT defined as intolerability, adverse
event, or inadequate efficacy of current psychotropic medication (at least 4 weeks
duration)

8. Agree to abide by the study protocol and its restrictions and be able to complete all
aspects of the study, including all visits and tests

9. Negative serum or urine pregnancy test (or history of hysterectomy)

10. Negative urine toxicology test (will only be completed at the request of the treating
clinician).

Exclusion Criteria:

1. Inability to speak English

2. Inability or lack of willingness to provide informed consent

3. Axis I or II disorder other than depression (i.e., by clinical assessment) that is the
primary reason for treatment

4. Psychotropic medication change (including dosage) between screening & baseline visit
with exception of no more than 8mg of Ativan within a 24-hour period.

5. Patients who meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)
criteria for any significant current substance use disorder other than nicotine or
caffeine. Must have at least early, partial or full, remission X 3 months

6. Clinically diagnosed cannabis use disorder, or SCID confirmed cannabis abuse or
dependence.

7. Current clinical diagnosis delirium, dementia, other cognitive disorders, or non-mood
psychotic disorder (i.e., schizophrenia, delusional disorder)

8. Index episode symptoms of hallucinations or delusions

9. Serious suicidal risk and/or in need of immediate hospitalization as judged by the
investigator

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

11. Significant unstable medical condition

12. Hepatic insufficiency (2.5 X upper limit of normal (ULN) for Aspartate
Aminotransferase (AST) or Alanine Aminotransferase (ALT) ), past liver transplant
recipient, and/or clinical diagnosis of cirrhosis of the liver

13. 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

14. Participation in another clinical trial within 30 days of the screening visit

15. Anticipated inability to attend scheduled study visits

16. Patients who in the judgment of the Investigator may be unreliable or uncooperative
with the evaluation procedure outlined in this protocol

17. Known cytochrome (CYP) & serotonin transporter genomic testing results within 5 years

18. A score of ≥15 on the Young Mania Rating Scale (YMRS)