GUIDED: Genomics Used to Improve DEpression Decisions

• Sponsor: Assurex Health Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02109939
• Collaborator: University of Michigan (Other)
• Enrollment: 1,398
• Locations: 61
• Arms: 2
• Actual Duration (Months): 40
• Patients Per Site: 22.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Evaluate the impact of GeneSight Psychotropic on response to psychotropic treatment as judged by the mean change in the 17-item Hamilton Depression (HAM-D17) score from baseline to end of Week 8 of the study.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder (MDD)	Genetic: GeneSight Psychotropic	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1398 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 12 Week, Randomized, Double-Blind, Controlled Evaluation Followed by an Open Label 12-Week Follow-up Period of the Impact of GeneSight Psychotropic on Response to Psychotropic Treatment in Outpatients Suffering From A Major Depressive Disorder (MDD) Having Had- Within the Current Episode- An Inadequate Response to at Least One Medication Included in GeneSight Psychotropic
• Actual Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Apr 20, 2017
• Actual Study Completion Date: Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: GeneSight Psychotropic Tested Subjects being tested with GeneSight Psychotropic	Genetic: 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 Names: Assurex Health GeneSight
Placebo Comparator: Treatment As Usual 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; 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 Names: Assurex Health GeneSight

Outcome Measures

Primary Outcome Measures

1. Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks [from baseline to end of Week 8]

   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.

Secondary Outcome Measures

1. Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks [from baseline to end of Week 8]

   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.

2. Percentage of Responders at Week 8 for HAM-D17 [Week 8 visit info]

   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.

3. Percentage of Responders at Week 12 for HAM-D17 [Week 12 visit info]

   *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.

4. Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7 [week 12 visit info]

   *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.

5. Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group; [week 8 visit info]

   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.

6. Time to Response/Remission of Depressive Symptoms Over 8 Weeks; [week 4 and 8 visit info]

   *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 or reported.

7. Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks [Baseline to week 24 visits]

   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.

8. Percentage of Responders at Week 8 for QIDS-C16 [Week 8 visit info]

   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.

9. Percentage of Responders at Week 8 for PHQ-9 [Week 8 visit info]

   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.

10. Percentage of Remitters at Week 12 Defined as QIDS-C16 ≤5 [week 12 visit info]

    *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.

11. Percentage of Remitters at Week 12 Defined as PHQ-9 <5 [week 12 visit info]

    *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.

12. Percentage of Remitters at Week 12 Defined as CGI-S ≤1 [week 12 visit info]

    *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.

13. Percentage of Responders at Week 12 for QIDS-C16 [Week 12 visit info]

    *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.

14. Percentage of Responders at Week 12 for PHQ-9 [Week 12 visit info]

    *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.

15. Percentage of Responders at Week 12 for CGI-S [Week 12 visit info]

    *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.

16. Percentage of Responders at Week 12 for CGI-I [Week 12 visit info]

    *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.

17. Percentage of Responders at Week 12 for CGI-EI [Week 12 visit info]

    *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.

18. Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group [week 8 visit info]

    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.

19. Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group [week 8 visit info]

    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.

20. Time to Response/Remission of Depressive Symptoms Over 12 Weeks; [week 4, 8, and 12 visit info]

    *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.

21. Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group [Baseline to week 24 visit info]

    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.

22. Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested Treatment Group [Baseline to week 24 visit info]

    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. *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.

Other Outcome Measures

1. Generalized Anxiety Disorder 7-item (GAD-7) Scale [week 12 to week 24]

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

2. Generalized Anxiety Disorder 7-item (GAD-7) Scale [baseline to week 8]

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

3. Generalized Anxiety Disorder 7-item (GAD-7) Scale [baseline to week 12]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Psychiatry Pharmaceutical Studies	Birmingham	Alabama	United States	35226
2	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
3	CiTrials	Bellflower	California	United States	90706
4	Catalina Research Institute	Chino	California	United States	91710
5	CiTrials	Costa Mesa	California	United States	92705
6	Synergy Research Center	Escondido	California	United States	92025
7	Pharmacology Research Institute	Los Alamitos	California	United States	90720
8	North County Research	Oceanside	California	United States	92056
9	CiTrials	Riverside	California	United States	92506
10	Stanford School of Medicine	Stanford	California	United States	94304
11	Viking Clinical Research	Temecula	California	United States	92591
12	Elite Clinical Trials, Inc	Wildomar	California	United States	92595
13	MCB Clinical Research Centers, LLC	Colorado Springs	Colorado	United States	80910
14	Howard University Hospital Mental Health Clinic	Washington	District of Columbia	United States	20060
15	Sarkis Clinical Trials	Gainesville	Florida	United States	32607
16	Clinical Neuroscience Solutions Healthcare	Jacksonville	Florida	United States	32256
17	Clinical Neuroscience Solutions	Orlando	Florida	United States	32801
18	Clinical Research Trials of Florida, Inc	Tampa	Florida	United States	33607
19	Stedman Clinical Trials	Tampa	Florida	United States	33613
20	Janus Center For Psychiatric Research	West Palm Beach	Florida	United States	33407
21	Atlanta Institute of Medicine and Research	Atlanta	Georgia	United States	30328
22	Mood and Anxiety Program at Emory University	Atlanta	Georgia	United States	30329
23	Meridian Clinical Research	Savannah	Georgia	United States	31406
24	Carman Research	Smyrna	Georgia	United States	30080
25	Rush University Medical Center	Chicago	Illinois	United States	60612
26	Behavioral Healthcare Associates	Schaumburg	Illinois	United States	60194
27	The Institute of Psychiatric Research	Indianapolis	Indiana	United States	46202
28	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
29	Kansas University Medical Center- Clinical Trials Unit	Wichita	Kansas	United States	67214
30	Pharmasite Research	Baltimore	Maryland	United States	21208
31	Johns Hopkins Hospital	Baltimore	Maryland	United States	21224
32	Geriatric Outpatient Unit- McLean Hospital	Belmont	Massachusetts	United States	02478
33	Boston Clinical Trials	Boston	Massachusetts	United States	02131
34	UMASS Center for Psychopharmacologic Research and Treatment	Worcester	Massachusetts	United States	01655
35	University of Michigan	Ann Arbor	Michigan	United States	48109
36	University of Minnesota	Minneapolis	Minnesota	United States	55454
37	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
38	PsychCare Consultants Research	Saint Louis	Missouri	United States	63128
39	Meridian Clinical Research	Bellevue	Nebraska	United States	68005
40	Premier Psychiatric Research Institute, LLC	Lincoln	Nebraska	United States	68526
41	United Medical Research Associates	Binghamton	New York	United States	13901
42	Integrative Clinical Trials, LLC	Brooklyn	New York	United States	11229
43	SPRI Clinical Trials	Brooklyn	New York	United States	11235
44	Eastside Comprehensive Medical Center, LLC	New York	New York	United States	10021
45	Finger Lakes Clinical Research	Rochester	New York	United States	14618
46	University of Cincinnati Health	Cincinnati	Ohio	United States	45267
47	Cleveland Clinic	Cleveland	Ohio	United States	44120
48	Ohio State University Department of Psychiatry	Columbus	Ohio	United States	43210
49	Midwest Clinical Research Center	Dayton	Ohio	United States	45417
50	Oklahoma Clinical Research Center	Oklahoma City	Oklahoma	United States	73112
51	Summit Research Network	Portland	Oregon	United States	97210
52	Suburban Research Associates	Media	Pennsylvania	United States	19063
53	Mood and Anxiety Disorders Treatment and Research	Philadelphia	Pennsylvania	United States	19104
54	Lincoln Research	Lincoln	Rhode Island	United States	02865
55	Clinical Neuroscience Solutions	Memphis	Tennessee	United States	38119
56	University of Texas Southwestern Medical Center	Dallas	Texas	United States	76034
57	Baylor College of Medicine	Houston	Texas	United States	77030
58	Alliance Research Group	Richmond	Virginia	United States	20230
59	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
60	Summit Research Network	Seattle	Washington	United States	98104
61	Frontier Institute	Spokane	Washington	United States	99204

Sponsors and Collaborators

• Assurex Health Inc.
• University of Michigan

Investigators

• Principal Investigator: John Greden, Ph.D, University of Michigan

Study Documents (Full-Text)

• Study Protocol - Apr 21, 2015
• Statistical Analysis Plan - Aug 17, 2016

More Information

Publications

None provided.

• Responsible Party: Assurex Health Inc.
• ClinicalTrials.gov Identifier: NCT02109939
• Other Study ID Numbers: ARX1006
• First Posted: Apr 10, 2014
• Last Update Posted: Jan 14, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Assurex Health Inc.: MDD; Pharmacogenomic; Pharmacogenomic Testing; Pharmacogenomics; Genetic Testing; Genetics; Major Depressive Disorder; GeneSight; Assurex; AssureRx; Psychotropic; Randomized; Double Blind; Placebo Controlled
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Psychotropic Drugs

Study Results

Participant Flow

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	681	717
COMPLETED	560	607
NOT COMPLETED	121	110

Baseline Characteristics

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	681	717	1398
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	597 87.7%	616 85.9%	1213 86.8%
>=65 years	84 12.3%	101 14.1%	185 13.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.9 (14.5)	48.0 (50.0)	47.5 (14.5)
Sex: Female, Male (Count of Participants)
Female	489 71.8%	498 69.5%	987 70.6%
Male	192 28.2%	219 30.5%	411 29.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	5 0.7%	3 0.4%	8 0.6%
Asian	12 1.8%	17 2.4%	29 2.1%
Native Hawaiian or Other Pacific Islander	1 0.1%	0 0%	1 0.1%
Black or African American	114 16.7%	94 13.1%	208 14.9%
White	538 79%	589 82.1%	1127 80.6%
More than one race	11 1.6%	14 2%	25 1.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	681 100%	717 100%	1398 100%
Baseline HAM-D17 (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.1 (4.20)	21.4 (4.22)	21.3 (4.21)

Outcome Measures

1. Primary Outcome

Title	Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks
Description	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.
Time Frame	from baseline to end of Week 8

Outcome Measure Data

Analysis Population Description

Per-Protocol

Arm/Group Title	Treatment As Usual	GeneSight Psychotropic Tested
Arm/Group Description	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.	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.
Measure Participants	607	560
Least Squares Mean (Standard Error) [percentage of change]	-24.39 (1.22)	-27.23 (1.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1070
	Comments
	Method	Mixed Models Analysis
	Comments	Repeated Measures including week 4.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.836
	Confidence Interval	(2-Sided) 95%; -6.285 to 0.613
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.758
	Estimation Comments

2. Secondary Outcome

Title	Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks
Description	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.
Time Frame	from baseline to end of Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual
Arm/Group Description	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.	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.
Measure Participants	621	677
Least Squares Mean (Standard Error) [percentage of change]	-35.107 (1.189)	-32.900 (1.147)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1822
	Comments
	Method	Mixed Models Analysis
	Comments	MMRM with week 4 data.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.207
	Confidence Interval	(2-Sided) 95%; -5.450 to 1.036
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.653
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Responders at Week 8 for HAM-D17
Description	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.
Time Frame	Week 8 visit info

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual
Arm/Group Description	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.	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.
Measure Participants	560	607
Number [percentage of subjects]	26.00	19.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0134
	Comments
	Method	Generalized linear mixed model
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Responders at Week 12 for HAM-D17
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7
Description	*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.
Time Frame	week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group;
Description	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.
Time Frame	week 8 visit info

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual
Arm/Group Description	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.	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.
Measure Participants	560	607
Number [percentage of subjects]	15.30	10.08

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments
	Method	Generalized linear mixed model
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 1.14 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Time to Response/Remission of Depressive Symptoms Over 8 Weeks;
Description	*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 or reported.
Time Frame	week 4 and 8 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks
Description	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.
Time Frame	Baseline to week 24 visits

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GeneSight Psychotropic Tested
Arm/Group Description	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.
Measure Participants	457
Mean (Standard Error) [percentage of change]	42.5 (1.52)

9. Secondary Outcome

Title	Percentage of Responders at Week 8 for QIDS-C16
Description	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.
Time Frame	Week 8 visit info

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	GeneSight Psychotropic Tested	Treatment As Usual
Arm/Group Description	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.	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.
Measure Participants	677	621
Number [percentage of subjects]	34.14	31.36

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2852
	Comments
	Method	Generalized linear mixed model.
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Responders at Week 8 for PHQ-9
Description	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.
Time Frame	Week 8 visit info

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Treatment As Usual	GeneSight Psychotropic Tested
Arm/Group Description	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.	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.
Measure Participants	676	620
Number [percentage of subjects]	31.63	39.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments
	Method	Generalized linear mixed model
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 1.14 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Remitters at Week 12 Defined as QIDS-C16 ≤5
Description	*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.
Time Frame	week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Percentage of Remitters at Week 12 Defined as PHQ-9 <5
Description	*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.
Time Frame	week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Percentage of Remitters at Week 12 Defined as CGI-S ≤1
Description	*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.
Time Frame	week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Percentage of Responders at Week 12 for QIDS-C16
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Percentage of Responders at Week 12 for PHQ-9
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Percentage of Responders at Week 12 for CGI-S
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Secondary Outcome

Title	Percentage of Responders at Week 12 for CGI-I
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Percentage of Responders at Week 12 for CGI-EI
Description	*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.
Time Frame	Week 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group
Description	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.
Time Frame	week 8 visit info

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Treatment As Usual	GeneSight Psychotropic Tested
Arm/Group Description	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.	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.
Measure Participants	677	621
Number [percentage of subjects]	15.62	20.89

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0140
	Comments
	Method	Generalized linear mixed model
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group
Description	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.
Time Frame	week 8 visit info

Outcome Measure Data

Analysis Population Description

Intent-to-treat

Arm/Group Title	Treatment As Usual	GeneSight Psychotropic Tested
Arm/Group Description	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.	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.
Measure Participants	677	620
Number [percentage of subjects]	14.79	18.58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment As Usual, GeneSight Psychotropic Tested
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0663
	Comments
	Method	Generalized linear mixed model
	Comments	The reported outcome measure is the estimated percentage from a generalized linear mixed model, not a simple count of subjects.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Time to Response/Remission of Depressive Symptoms Over 12 Weeks;
Description	*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.
Time Frame	week 4, 8, and 12 visit info

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group
Description	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.
Time Frame	Baseline to week 24 visit info

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	GeneSight Psychotropic Tested
Arm/Group Description	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.
Measure Participants	457
Number [percentage of subjects]	44.3

23. Secondary Outcome

Title	Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested Treatment Group
Description	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. *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.
Time Frame	Baseline to week 24 visit info

Outcome Measure Data

Analysis Population Description

Per Protocol

Arm/Group Title	GeneSight Psychotropic Tested
Arm/Group Description	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.
Measure Participants	457
Number [percentage of subjects]	31.1

24. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Other Pre-specified Outcome

Title	Generalized Anxiety Disorder 7-item (GAD-7) Scale
Description	The mean change in Generalized Anxiety Disorder 7-item (GAD-7) scale from baseline to week 8
Time Frame	baseline to week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

26. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	8 weeks
Arm/Group Title	GeneSight Psychotropic Tested		Treatment As Usual
Arm/Group Description	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.		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.
All Cause Mortality
	GeneSight Psychotropic Tested		Treatment As Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/681 (0%)		0/717 (0%)
Serious Adverse Events
	GeneSight Psychotropic Tested		Treatment As Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/681 (0.4%)		2/717 (0.3%)
Gastrointestinal disorders
Gastrointestinal hemorrhage	0/681 (0%)	0	1/717 (0.1%)	1
General disorders
non cardiac chest pains	0/681 (0%)	0	1/717 (0.1%)	1
Metabolism and nutrition disorders
transient hypoglycemia	1/681 (0.1%)	1	0/717 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle twitching	1/681 (0.1%)	1	0/717 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/681 (0.1%)	1	0/717 (0%)	0
Other (Not Including Serious) Adverse Events
	GeneSight Psychotropic Tested		Treatment As Usual
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/681 (0%)		0/717 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.