Genomics Used to Improve DEpression Decisions | NCT02109939

Status Module

Name	Class
University of Michigan	OTHER

Description Module

Detailed Description

Major depressive disorder (MDD) is a highly prevalent (Hasin et al., 2005) mental disorder and a leading source of disease burden worldwide (Lopez et al., 2006). Epidemiological studies estimate 12-month and lifetime prevalence for MDD in the United States to be 5.3% and 13.2%, respectively (reviewed in Blanco et al., 2010). MDD is expected to be the second greatest cause of disability by 2020 and has been shown to cause significant morbidity, affecting people's ability to work, function in relationships, and engage in social activities. Moreover, MDD increases the risk of suicidal ideation, attempted suicide, and death by completed suicide.

Prospective longitudinal studies of patient samples show that MDD is a chronic illness, characterized by remitting and recurrent depressive episodes (Solomon et al., 1997; Mueller et al., 1999). A major depressive episode is characterized by a low mood or an inability to experience pleasure (anhedonia), or both, for more than 2 weeks, combined with several cognitive and vegetative symptoms and the occurrence of distress or impairment (reviewed in Rot et al., 2009). In the US, nearly 1 in 5 people will experience a major depressive episode at some point in their lives (reviewed in Rot et al., 2009). Drugs currently available to treat depression fall into the categories of those that have their main effect by increasing norepinephrine (NE) (the tricyclic or tetracyclic antidepressants [TCAs]), those that increase serotonin (5-HT) (the selective serotonin reuptake inhibitors [SSRIs]), and those that increase both NE and 5-HT (the monoamine oxidase inhibitors [MAOIs] and the serotonin and norepinephrine reuptake inhibitors [SNRIs]). While all antidepressants achieve similar levels of efficacy, treatment failures are relatively high ranging from 30 to 60% (Simpson and DePaulo). Additionally, many of these compounds are associated with significant adverse events (AEs).

The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications.

The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes.

Tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

The clinical utility of GeneSight Psychotropic has been evaluated in three previous prospective trials. Hall-Flavin et al reported the results of an open-label pilot study (n = 44) comparing GeneSight guided treatment to treatment as usual (TAU) without the benefit of pharmacogenomic testing (2012). The GeneSight guided arm demonstrated a 30.8% improvement in HAM-D17 score by the end of the 8 week treatment period, compared to an 18.2% improvement in the TAU arm (p = 0.04). Results of the larger (n = 165) open-label trial (Hall-Flavin, et al 2013) mirrored these findings, demonstrating a 46.9% improvement in HAMD17 score in the GeneSight arm, compared to a 29.9% improvement in the TAU arm (p < 0.0001). The third trial used a randomized, double-blind trial design (n = 51). Due to the small sample size, the trial was underpowered to detect a significant difference in improvement between the two arms (TAU and GeneSight). However, effect sizes of improvement reflected those seen in previous trials. The GeneSight group experienced a 30.8% improvement in HAMD17, compared to 20.7% in TAU. Odds ratios for response were calculated, showing that GeneSight-guided subjects had a 2.14 times greater likelihood of response compared to TAU subjects, which was similar to the 4.67 (smaller trial) and 2.06 (larger trial) odds ratios calculated for the other two studies.

Previous studies utilizing an open-label design have shown significant improvement in patient outcomes following use of the GeneSight test. However, although effect sizes were similar to those seen in the open-label studies, a small (n = 51) blinded, randomized controlled trial did not detect a statistically significant outcome. Therefore, the primary rationale for this trial is to replicate previous findings of improvement in clinical outcomes in subjects treated with the benefit of GeneSight testing utilizing a double-blind, randomized control trial (RCT) design.

It is expected that results from this trial will be used to inform guidelines for the use of pharmacogenomic testing for the treatment of major depressive disorder. Results may also be shared with regulatory bodies in the United States and abroad.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GeneSight Psychotropic Tested	Active Comparator	Subjects being tested with GeneSight Psychotropic	Genetic: GeneSight Psychotropic
Treatment As Usual	Placebo Comparator	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm until after week 12.	Genetic: GeneSight Psychotropic

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GeneSight Psychotropic	Genetic	The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks	Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean percent change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 8 of the study. Scores range from 0 to 50, and lower scores are better outcomes. Percent change is defined as (week 8 score -baseline score) / (baseline score) x 100.	from baseline to end of Week 8

Secondary Outcomes

Measure	Description	Time Frame
Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks	Mean percent change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) score from baseline to end of Week 8 of the study. Scores range from 0 to 27 with lower scores being better outcomes. Percent change is defined as (week 8 score - baseline score) / (baseline score) x 100.

Other Outcomes

Measure	Description	Time Frame
Generalized Anxiety Disorder 7-item (GAD-7) Scale	The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from week 12 to week 24	week 12 to week 24
Generalized Anxiety Disorder 7-item (GAD-7) Scale

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Be able to understand the requirements of the study and provide written informed consent to participate in this study; a signed and dated ICF will be obtained from each patient before participation in the study;
Have provided written authorization for the use and disclosure of their protected health information;
Be ≥18 years of age;
Suffer from a Major Depressive Episode meeting DSM-IV-TR criteria;
Have had an inadequate response within the current episode to at least 1 psychotropic treatment. Inadequate response is defined as inadequate efficacy after 6 weeks of a psychotropic treatment or discontinuation of a psychotropic treatment due to AEs or intolerability;
Have a total baseline score on the QIDS-C16 and QIDS-SR16 rating scale ≥11;
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.

Exclusion Criteria:

Patients posing a serious suicidal risk and/or in need of immediate hospitalization as judged by the investigator;
Patients with a diagnosis of Bipolar I or II disorder;
Patients with a current Axis I diagnosis of:
1. Delirium
2. Dementia
3. Amnestic and other cognitive disorder
4. Schizophrenia or other psychotic disorder;
Patients having experienced hallucinations, delusions, or any psychotic symptomatology within the current depressive episode or during prior depressive episodes;
Patient is currently in an inpatient facility;
Patients with a history of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic or euthyroid for 6 months;
Patients who meet DSM-IV-TR criteria for any significant current substance use disorder;
Patients with significant unstable medical condition; life threatening disease; hepatic insufficiency (3X ULN for AST and/or ALT); 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;
Participation in another clinical trial within 30 days of the screening visit;
Anticipated inability to attend scheduled study visits;
Patients who in the judgment of the Investigator may be unreliable or uncooperative with the evaluation procedure outlined in this protocol;
Patients with a history of prior pharmacogenomic testing;
Any change in psychotropic medication (including change in dosage) between screening and randomization;
Patients receiving ECT, DBS or TMS treatment (should a Subject receive any of these treatments they must be discontinued from the study);
Patients who are known to be pregnant or lactating;
Patients with a history of gastric bypass surgery.

Name	Affiliation	Role
John Greden, Ph.D	University of Michigan	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Birmingham Psychiatry Pharmaceutical Studies		Birmingham	Alabama	35226	United States
University of Alabama at Birmingham

PubMed Identifier	Type	Citation	Retractions
31881956	Derived	Dunlop BW, Parikh SV, Rothschild AJ, Thase ME, DeBattista C, Conway CR, Forester BP, Mondimore FM, Shelton RC, Macaluso M, Logan J, Traxler P, Li J, Johnson H, Greden JF. Comparing sensitivity to change using the 6-item versus the 17-item Hamilton depression rating scale in the GUIDED randomized controlled trial. BMC Psychiatry. 2019 Dec 27;19(1):420. doi: 10.1186/s12888-019-2410-2.
31721487

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 21, 2015	Jul 16, 2019

Arm/Group Information

ID	Title	Description
BG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.
BG001	Treatment As Usual	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00046.9± 14.5 BG00148.0± 50.0 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000489 BG001498 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0005 BG0013 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000681 BG001717 BG002

Baseline HAM-D17

HAM-D17 score at baseline

Mean

Standard Deviation

units on a scale

Title

Denominators

Categories

Title	Measurements
	BG00021.1± 4.20 BG00121.4± 4.22 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks

Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean percent change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 8 of the study. Scores range from 0 to 50, and lower scores are better outcomes. Percent change is defined as (week 8 score -baseline score) / (baseline score) x 100.

Per-Protocol

Posted

Least Squares Mean

Standard Error

percentage of change

from baseline to end of Week 8

ID	Title	Description
OG000	Treatment As Usual	This group of subjects will not have treatment guided by their GeneSight results or know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.
OG001	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic. This group of subjects will not know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.

Units	Counts
Participants	OG000607 OG001560

Title

Denominators

Categories

Title	Measurements
	OG000-24.39± 1.22 OG001-27.23± 1.27

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis	Repeated Measures including week 4.	0.1070		Mean Difference (Net)	-2.836	Standard Error of the Mean	1.758	2-Sided	95	-6.285	0.613					Superiority

Secondary

Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks

Mean percent change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) score from baseline to end of Week 8 of the study. Scores range from 0 to 27 with lower scores being better outcomes. Percent change is defined as (week 8 score - baseline score) / (baseline score) x 100.

Intent-to-Treat

Posted

Least Squares Mean

Standard Error

percentage of change

from baseline to end of Week 8

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic. This group of subjects will not know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.
OG001	Treatment As Usual	This group of subjects will not have treatment guided by their GeneSight results or know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Responders at Week 8 for HAM-D17

Adjusted percentage of responders at Week 8 in each treatment group on the 17-item Hamilton Depression Rating Scale (HAM-D17). A responder is defined as a participant with at least a 50% decrease from baseline in total scale score. Scores range from 0 to 50, and lower scores are better outcomes.

Per Protocol

Posted

Number

percentage of subjects

Week 8 visit info

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.
OG001	Treatment As Usual	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Responders at Week 12 for HAM-D17

*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding might have occurred for some patients prior to week 12 assessments, data collected at week 12 were no longer considered blinded and are not analyzed or reported.

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7

Not Posted

week 12 visit info

Participants

Secondary

Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group;

Adjusted percentage of remitters at Week 8 defined as a score ≤7 in the 17-item Hamilton Depression Rating Scale (HAM-D17) in each treatment group. Scores range from 0 to 50, and lower scores are better outcomes.

Per Protocol

Posted

Number

percentage of subjects

week 8 visit info

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.
OG001	Treatment As Usual	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Time to Response/Remission of Depressive Symptoms Over 8 Weeks;

Not Posted

week 4 and 8 visit info

Participants

Secondary

Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks

Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean percent change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 24 of the study. Scores range from 0 to 50, and lower scores are better outcomes. Percent change is defined as (week 24 score -baseline score) / (baseline score) x 100.

Per Protocol - Due to unblinding before week 12 there was no longer a treatment as usual and guided treatment arm and it was pre-specified in the Protocol to include only the GeneSight Psychotropic Tested Arm/Group for this Outcome Measure

Posted

Mean

Standard Error

percentage of change

Baseline to week 24 visits

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Responders at Week 8 for QIDS-C16

Adjusted percentage of responders at Week 8 in each treatment group on the 16-item Quick Inventory of Depression Symptomology (QIDS-C16). A responder is defined as a participant with at least 50% decrease from baseline in total scale score. Scores range from 0 to 27 with lower scores being better outcomes.

Intent-to-treat

Posted

Number

percentage of subjects

Week 8 visit info

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.
OG001	Treatment As Usual	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Responders at Week 8 for PHQ-9

Adjusted percentage of responders at Week 8 in each treatment group on the 9-item Patient Health Questionnaire (PHQ-9). A responder is defined as a participant with at least 50% decrease from baseline in total scale score. Scores range from 0 to 27 with lower scores being better outcomes.

Intent-to-treat

Posted

Number

percentage of subjects

Week 8 visit info

ID	Title	Description
OG000	Treatment As Usual	This group of subjects will not have treatment guided by their GeneSight results or know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.
OG001	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic. This group of subjects will not know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Remitters at Week 12 Defined as QIDS-C16 ≤5

Not Posted

week 12 visit info

Participants

Secondary

Percentage of Remitters at Week 12 Defined as PHQ-9 <5

Not Posted

week 12 visit info

Participants

Secondary

Percentage of Remitters at Week 12 Defined as CGI-S ≤1

Not Posted

week 12 visit info

Participants

Secondary

Percentage of Responders at Week 12 for QIDS-C16

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Responders at Week 12 for PHQ-9

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Responders at Week 12 for CGI-S

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Responders at Week 12 for CGI-I

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Responders at Week 12 for CGI-EI

Not Posted

Week 12 visit info

Participants

Secondary

Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group

Adjusted percentage of remitters at Week 8 in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) in each treatment group. A remitter is defined as a subject with a score ≤ 5. Scores range from 0 to 27 with lower scores being better outcomes.

Intent-to-treat

Posted

Number

percentage of subjects

week 8 visit info

ID	Title	Description
OG000	Treatment As Usual	This group of subjects will not have treatment guided by their GeneSight results or know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.
OG001	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic. This group of subjects will not know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group

Adjusted percentage of remitters at Week 8 in each treatment group on the 9-item Patient Health Questionnaire (PHQ-9). A remitter is defined as a participant with score <5 on the PHQ-9. Scores range from 0 to 27 with lower scores being better outcomes.

Intent-to-treat

Posted

Number

percentage of subjects

week 8 visit info

ID	Title	Description
OG000	Treatment As Usual	This group of subjects will not have treatment guided by their GeneSight results or know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.
OG001	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic. This group of subjects will not know whether they are in a particular arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. Tricyclic antidepressants, one MAOI, and typical and atypical antipsychotics are also represented.

Secondary

Time to Response/Remission of Depressive Symptoms Over 12 Weeks;

*Comment*: Time to response/remission is not an outcome measure that can accurately be reported from the way the data was collected. As specified in the updated SAP before the blind was broken, this was not analyzed and reported. Additionally, for patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding may have occurred prior to week 12 assessments, data collected at week 12 were considered unblinded and are not reported.

Not Posted

week 4, 8, and 12 visit info

Participants

Secondary

Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group

Adjusted percentage of responders at Week 24 in the GeneSight Psychotropic Tested treatment group on the 17-item Hamilton Depression Rating Scale (HAM-D17). A responder is defined as a participant with at least a 50% decrease from baseline in total scale score. Scores range from 0 to 50, and lower scores are better outcomes.

Per Protocol

Posted

Number

percentage of subjects

Baseline to week 24 visit info

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Units	Counts
Participants

Secondary

Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested Treatment Group

*Comment*: For patients in TAU, clinicians were blinded to the pharmacogenomic test result until after completion of the week 8 visit. Because unblinding may have occurred prior to week 12 assessments, all data collected at week 12 were considered unblinded and are not reported.

Per Protocol

Posted

Number

percentage of subjects

Baseline to week 24 visit info

ID	Title	Description
OG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.

Other Pre-specified

Generalized Anxiety Disorder 7-item (GAD-7) Scale

The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from week 12 to week 24

Not Posted

week 12 to week 24

Participants

Other Pre-specified

Generalized Anxiety Disorder 7-item (GAD-7) Scale

The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from baseline to week 8

Not Posted

baseline to week 8

Participants

Other Pre-specified

Generalized Anxiety Disorder 7-item (GAD-7) Scale

The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from baseline to week 12

Not Posted

baseline to week 12

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GeneSight Psychotropic Tested	Subjects being tested with GeneSight Psychotropic GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.	0	681	3	681	0	681
EG001	Treatment As Usual	This group of subjects will not see their GeneSIght results or know whether or not they are in either arm. GeneSight Psychotropic: The GeneSight Psychotropic product is a pharmacogenomic decision support tool that helps clinicians to make informed, evidence-based decisions about proper drug selection, based on the testing for clinically important genetic variants in multiple pharmacokinetic and pharmacodynamic genes that affect a patient's ability to tolerate or respond to medications. The GeneSight Psychotropic product contains the most commonly prescribed antidepressant and antipsychotic medications, including a full representation of the SSRI and SNRI drug classes. tricyclic antidepressants, an MAOI, and typical and atypical antipsychotics are also represented.	0	717	2	717	0	717

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected681 at risk EG0010 events0 affected717 at risk
Muscle twitching	Musculoskeletal and connective tissue disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected681 at risk EG0010 events0 affected717 at risk
Gastrointestinal hemorrhage	Gastrointestinal disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected681 at risk EG0011 events1 affected717 at risk
transient hypoglycemia	Metabolism and nutrition disorders	MedDRA (Unspecified)	Systematic Assessment	EG0001 events1 affected681 at risk EG0010 events0 affected717 at risk
non cardiac chest pains	General disorders	MedDRA (Unspecified)	Systematic Assessment	EG0000 events0 affected681 at risk EG0011 events1 affected717 at risk

ID	Term
D003866	Depressive Disorder
D019964	Mood Disorders
D001523	Mental Disorders