Major Depressive Disorder (MDD)
Conditions
Keywords
MDD, Pharmacogenomic, Pharmacogenomic Testing, Pharmacogenomics, Genetic Testing, Genetics, Major Depressive Disorder, GeneSight, Assurex, AssureRx, Psychotropic, Randomized, Double Blind, Placebo Controlled
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.
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.
Interventions
GENETICGeneSight 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.
Sponsors
University of Michigan
Assurex Health Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 681 |
| 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. | 717 |
| Total | 1,398 |
Baseline characteristics
| Characteristic | GeneSight Psychotropic Tested | Treatment As Usual | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 84 Participants | 101 Participants | 185 Participants |
| Age, Categorical Between 18 and 65 years | 597 Participants | 616 Participants | 1213 Participants |
| Age, Continuous | 46.9 years STANDARD_DEVIATION 14.5 | 48.0 years STANDARD_DEVIATION 50 | 47.5 years STANDARD_DEVIATION 14.5 |
| Baseline HAM-D17 | 21.1 units on a scale STANDARD_DEVIATION 4.2 | 21.4 units on a scale STANDARD_DEVIATION 4.22 | 21.3 units on a scale STANDARD_DEVIATION 4.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 17 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 114 Participants | 94 Participants | 208 Participants |
| Race (NIH/OMB) More than one race | 11 Participants | 14 Participants | 25 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 538 Participants | 589 Participants | 1127 Participants |
| Region of Enrollment United States | 681 participants | 717 participants | 1398 participants |
| Sex: Female, Male Female | 489 Participants | 498 Participants | 987 Participants |
| Sex: Female, Male Male | 192 Participants | 219 Participants | 411 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 681 | 0 / 717 |
| other Total, other adverse events | 0 / 681 | 0 / 717 |
| serious Total, serious adverse events | 3 / 681 | 2 / 717 |
Outcome results
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.
Time frame: from baseline to end of Week 8
Population: Per-Protocol
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment As Usual | Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks | -24.39 percentage of change | Standard Error 1.22 |
| GeneSight Psychotropic Tested | Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 8 Weeks | -27.23 percentage of change | Standard Error 1.27 |
p-value: 0.10795% CI: [-6.285, 0.613]Mixed Models Analysis
Secondary
Percentage of Remitters at Week 12 Defined as CGI-S ≤1
\*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
Secondary
Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7
\*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
Secondary
Percentage of Remitters at Week 12 Defined as PHQ-9 <5
\*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
Secondary
Percentage of Remitters at Week 12 Defined as QIDS-C16 ≤5
\*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
Secondary
Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested 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. \*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
Population: Per Protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Remitters at Week 24 Defined as HAM-D17 ≤7 in the GeneSight Psychotropic Tested Treatment Group | 31.1 percentage of subjects |
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.
Time frame: week 8 visit info
Population: Per Protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group; | 15.30 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Remitters at Week 8 Defined as HAM-D17 ≤7 Each Treatment Group; | 10.08 percentage of subjects |
p-value: 0.006695% CI: [1.14, 2.27]Generalized linear mixed model
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.
Time frame: week 8 visit info
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group | 14.79 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Remitters at Week 8 Defined as PHQ-9 <5 in Each Treatment Group | 18.58 percentage of subjects |
p-value: 0.066395% CI: [0.98, 1.76]Generalized linear mixed model
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.
Time frame: week 8 visit info
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group | 15.62 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Remitters at Week 8 Defined as QIDS-C16 ≤ 5 in Each Treatment Group | 20.89 percentage of subjects |
p-value: 0.01495% CI: [1.07, 1.89]Generalized linear mixed model
Secondary
Percentage of Responders at Week 12 for CGI-EI
\*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
Secondary
Percentage of Responders at Week 12 for CGI-I
\*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
Secondary
Percentage of Responders at Week 12 for CGI-S
\*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
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.
Time frame: Week 12 visit info
Secondary
Percentage of Responders at Week 12 for PHQ-9
\*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
Secondary
Percentage of Responders at Week 12 for QIDS-C16
\*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
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.
Time frame: Baseline to week 24 visit info
Population: Per Protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Responders at Week 24 for HAM-D17 in the GeneSight Psychotropic Tested Treatment Group | 44.3 percentage of subjects |
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.
Time frame: Week 8 visit info
Population: Per Protocol
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Responders at Week 8 for HAM-D17 | 26.00 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Responders at Week 8 for HAM-D17 | 19.92 percentage of subjects |
p-value: 0.013495% CI: [1.07, 1.86]Generalized linear mixed model
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.
Time frame: Week 8 visit info
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Responders at Week 8 for PHQ-9 | 31.63 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Responders at Week 8 for PHQ-9 | 39.74 percentage of subjects |
p-value: 0.002395% CI: [1.14, 1.79]Generalized linear mixed model
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.
Time frame: Week 8 visit info
Population: Intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment As Usual | Percentage of Responders at Week 8 for QIDS-C16 | 34.14 percentage of subjects |
| GeneSight Psychotropic Tested | Percentage of Responders at Week 8 for QIDS-C16 | 31.36 percentage of subjects |
p-value: 0.285295% CI: [0.9, 1.43]Generalized linear mixed model.
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.
Time frame: from baseline to end of Week 8
Population: Intent-to-Treat
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Treatment As Usual | Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks | -35.107 percentage of change | Standard Error 1.189 |
| GeneSight Psychotropic Tested | Percent Change in the 16-item Quick Inventory of Depression Symptomology (QIDS-C16) Score From Baseline to 8 Weeks | -32.900 percentage of change | Standard Error 1.147 |
p-value: 0.182295% CI: [-5.45, 1.036]Mixed Models Analysis
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.
Time frame: Baseline to week 24 visits
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment As Usual | Percent Change in the 17-item Hamilton Depression (HAM-D17) Score From Baseline to 24 Weeks | 42.5 percentage of change | Standard Error 1.52 |
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.
Time frame: week 4, 8, and 12 visit info
Secondary
Time to Response/Remission of Depressive Symptoms Over 8 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 or reported.
Time frame: week 4 and 8 visit info
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
Time frame: week 12 to week 24
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
Time frame: baseline to week 8
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
Time frame: baseline to week 12