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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
1,398
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.
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
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
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
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
Percentage of Remitters at Week 12 Defined as HAM-D17 ≤7
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Birmingham Psychiatry Pharmaceutical Studies
Birmingham, Alabama, United States
University of Alabama at Birmingham
Birmingham, Alabama, United States
CiTrials
Bellflower, California, United States
Catalina Research Institute
Chino, California, United States
CiTrials
Costa Mesa, California, United States
Synergy Research Center
Escondido, California, United States
Pharmacology Research Institute
Los Alamitos, California, United States
North County Research
Oceanside, California, United States
CiTrials
Riverside, California, United States
Stanford School of Medicine
Stanford, California, United States
...and 51 more locations
\*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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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