McLean and Genomind Prospective Study

Importance / Relevance:

Psychiatric disorders are etiologically complex and clinically heterogeneous which makes them
challenging to diagnose and effectively treat. Thus, they pose a huge societal burden and
involve substantial costs in human and financial terms. Specifically in the U.S., mental
health disorders including MDD and PTSD account for 6.2% of the nation's health care
spending. Major depressive disorder and schizophrenia are listed by the World Health
Organization as being among the top 10 leading causes of years lost due to disability.

The primary means of treating major mental illness remains psychotropic-based, whether alone
or in combination with psychotherapy. Despite an ever-growing number of medication options,
however, outcomes remain significantly suboptimal. In the landmark Sequenced Treatment
Alternatives to Relieve Depression (STAR*D) study, only 37% achieved remission with
first-line therapy with a selective serotonin reuptake inhibitor (SSRI), whereas 16.3%
withdrew completely from treatment due to drug intolerance. In the Clinical Antipsychotic
Trails of Intervention Effectiveness (CATIE), over 74% eventually discontinued study
medication either because of lack of efficacy or tolerability. And in the Systematic
Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial, up to 75% patients
experienced symptoms relapse over the course of follow-up.

With the advent of the genomics revolution, and precision and personalized medicine,
tailoring patients' medication treatment to their individual pharmacokinetic and
pharmacodynamic characteristics is being increasingly embraced by various fields of medicine.
Testing is currently available for cardiovascular, cancer, autoimmune, infectious, and
psychiatric illnesses, etc. In fact, over 140 US Food and Drug Administration (FDA)-approved
drugs have pharmacogenomic-based guidelines; at least 27 of these are psychotropics,
including Celexa for which the FDA specially recommend dose-reduction for P450 CYP2C19 poor
metabolizers due to the risk of QT prolongation (FDA, 2014). Yet the vast majority of
Celexa-prescribing clinicians are unaware of which of their patients are among the 3% of poor
metabolizers or the 20% of the intermediate metabolizers who are also at increased risk.

Genomind, a Pennsylvania-based personalized medicine company, provides genetic testing with
the Genecept™ Assay that can help clinicians optimize treatment for their patients with
mental illness. This test is an alternative to the traditional trial and error approach to
psychiatric drug prescribing which fails approximately 50% of the time.

The Genecept Assay identifies patient-specific genetic markers that indicate which treatments
are likely to work as intended, be ineffective, or cause adverse effects. The assay is easily
administered by a cheek swab test and analyzes variations in key genes that can inform
treatment decisions. The assay is used to guide treatment for a broad range of psychiatric
conditions including depression, anxiety, obsessive-compulsive disorder (OCD), attention
deficit hyperactivity disorder (ADHD), bipolar disorder, post-traumatic stress disorder
(PTSD), autism, schizophrenia, chronic pain and substance abuse. Each test provides
clinicians with an easy-to-read patient report and complimentary psychopharmacogenomic
consultation with Genomind's expert scientific staff (including Physicians, PhDs, and
PharmDs). Additionally, the assay has been shown in peer reviewed published studies to
improve patient outcomes and reduce overall medical costs.

Brief summary of procedures and recruitment:

This is a six month naturalistic prospective, randomized, open label study of pharmacogenetic
testing and clinical outcomes in inpatients across diagnoses, including Treatment Resistant
Depression (TRD) with or without Post-Traumatic Stress Disorder (PTSD), recruiting from the
Short Term Unit at McLean Hospital.

Specifically the investigators will enroll 200 inpatient subjects over 2 years who will
donate saliva/undergo a cheek swab to collect DNA for the Genecept assay. For 100 patients in
the assay-guided group, treating Clinicians will receive the Genecept report prior to patient
discharge and use it to guide psychoeducation and medication management. For the additional
100 inpatients, treating clinicians will not receive the report during the patient's
inpatient stay (treatment as usual. Clinicians will receive the assay report for patients in
the treatment-as-usual group at the 3-month followup period. Thus this group will serve as
the control group for the outcomes related to Genecept-guided decision making.

Primary Objectives:

Objective 1: Does Inpatient Genetic Testing Improve Symptoms at Follow-up: This aim will test
if, by the 3-month follow-up, inpatient psychopharmacogenetic testing will reduce symptoms of
depression and anxiety.

Objective 2: Does Inpatient Genetic Testing Improve Readmission: This aim will test if, by
the 3-month follow-up, inpatient psychopharmacogenetic testing will reduce frequency of
inpatient readmission.

Secondary Objectives:

Objective 3: Does Inpatient Genetic Testing Improve Discharge Measures: This aim will test
if, by discharge, inpatient psychopharmagogenetic testing enhances measures of patient
satisfaction, and symptom measurement.

Objective 4: Does Inpatient Genetic Testing Improve Follow-up Measures: This aim will test
if, by the time of 3-month and 6-month follow-up, inpatient psychopharmacogenetic testing
will increase measures of follow-up treatment compliance, reduce time to stable medication
regimen; and suicide attempts; reduce self-medication with substance of abuse.

Objective 5: Does Inpatient Genetic Testing Improve Medication Management: This aim will
test, if when examined retrospectively across the discharge and 3-month data and 6-month
data, inpatient psychopharmacogenetic testing will improve medication adherence, reduce
number of medication trials, and reduce time-to-effective dose.

Inclusion Criteria:

- Inpatients admitted to the Short Term Unit at Mclean Ability to understand and sign
informed consent. These patients cover a transdiagnostic range of severe depression,
anxiety, and PTSD.

- Both genders, all ethnic backgrounds, age 18 or older

- Fluent English speakers

Exclusion Criteria:

- Involuntary hospitalization