Major Depression
Conditions
Keywords
Treatment, Pharmacogenetics, Depression
Brief summary
The focus of this application is on the impact of providing depressed Veterans and their providers with the results of pharmacogenetic (PGx) testing for psychotropic medications. The project focuses on whether and how patients and providers use genetic test results given to them at the time an antidepressant is to be initiated to treat Major Depressive Disorder (MDD) and whether use of the test results improves patient outcomes. MDD is one of the most common conditions associated with military service and combat exposure, increases suicide risk, and worsens the course of common medical conditions, making it a leading cause of functional impairment and mortality. Validation of a PGx test to personalize the treatment of MDD represents an important opportunity to improve the healthcare of Veterans.
Detailed description
Background: In the last several years, commercial pharmacogenetic (PGx) testing for psychotropic medications has become widespread as a means of implementing precision medicine, with some insurers electing to cover the cost of testing. These developments have put increasing pressure on the Veterans Health Administration to implement a mental health focused PGxs program, especially for treating depression, but without sufficient scientific study to support the utility of clinical application. Objectives: The investigators propose a program of research to evaluate the utility of PGx testing in treating Major Depressive Disorder. Methods: The investigators plan a multi-site RCT (n=2000), patient/provider dyads will be randomly assigned to receive results of the PGx battery right after randomization (i.e. intervention group) or after 6 months of treatment as usual (i.e. delayed results group)The study will test the following hypotheses: 1. Veterans with MDD whose care is guided by the results of the PGx battery (the intervention group) will have a higher rate of remission of depression than the delayed results group. (Primary Hypothesis) 2. Provider/patient dyads in the intervention group will use fewer medications that have potential gene-drug interactions based on commercial PGx test results than dyads in the delayed results group (Primary Hypothesis).
Interventions
OTHERPharmacogenetic Test
The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
The study intervention is the provision of pharmacogenetic test results which can then be used to choice appropriate medication.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* PHQ-9 score 10 and a presumptive diagnosis of MDD per PHQ-9 criteria * at least one prior treatment exposure for MDD (psychotherapy or antidepressant * intent to start treatment of the MDD with an antidepressant, simple dose increases will not be considered inclusionary * willingness to provide signed, informed consent to participate in the study
Exclusion criteria
* current serious co-occurring psychiatric illness, i.e.: * schizophrenia * bipolar disorder * psychotic major depression * borderline or antisocial personality disorder * eating disorder * active alcohol or other drug use disorder * current use of an antipsychotic medication * augmentation therapy, e.g.: * use of two or more antidepressants at the time of randomization (trazodone at a dosage \< 150 mg/day will not be considered augmentation and thus allowed) * patients requiring urgent care or inpatient hospitalization at the time of consent * currently incarcerated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression Remission | 24 weeks post randomization | The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. Remission was defined as a score of 5 or less at the endpoint. the reported number of participants are those reaching that threshold of symptoms. |
| Use of Fewer Medications That Have Potential Gene-drug Interactions | Over the first 30 days | The investigators will examine the proportion of antidepressants prescribed in the first 30 days of the trial that have the potential for gene-drug interactions. The chance for a gene-drug interaction was classified as 1. the subject did not have a prescription for an antidepressant during the initial 4 weeks of the trial (No Antidepressant), 2 the subject was prescribed an antidepressant with no known gene-drug interaction (No Gene Interaction), 3 the subject was prescribed an antidepressant with moderate gene-drug interactions (Moderate Interaction). These are also gene-drug interactions that do not have level A concordance. And 4. the subject was prescribed an antidepressant with substantial gene-drug interactions or gene-drug interactions that are considered to have a high level of evidence to support other prescribing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Severity | 24 Weeks | The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self-assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. This measure will use the PHQ9 as a continuous measure. The reported outcome is the difference in scores from baseline to 24 weeks. |
| Depression Response | 24 weeks | The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. Response was measured by a 50% reduction in scores from baseline to each time point. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Group Pharmacogenetic test results will be provided to the provider within 72 hours of randomization in order to facilitate choice in selecting antidepressants.
Pharmacogenetic Test: The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications. | 966 |
| Delay Results Group The comparator arm will not receive results at the time of randomization but will get results after the 24 week assessment (thus the results are delayed). | 978 |
| Total | 1,944 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 2 |
| Overall Study | Lost to Follow-up | 187 | 167 |
| Overall Study | Withdrawal by Subject | 23 | 22 |
Baseline characteristics
| Characteristic | Intervention Group | Delay Results Group | Total |
|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 15 | 47 years STANDARD_DEVIATION 15 | 48 years STANDARD_DEVIATION 15 |
| Depression severity | 17.5 units on a scale STANDARD_DEVIATION 4.3 | 17.5 units on a scale STANDARD_DEVIATION 4.3 | 17.5 units on a scale STANDARD_DEVIATION 4.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 113 Participants | 104 Participants | 217 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 850 Participants | 869 Participants | 1719 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 10 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 24 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 185 Participants | 167 Participants | 352 Participants |
| Race (NIH/OMB) More than one race | 90 Participants | 84 Participants | 174 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) White | 644 Participants | 688 Participants | 1332 Participants |
| Region of Enrollment United States | 966 Participants | 978 Participants | 1944 Participants |
| Sex: Female, Male Female | 229 Participants | 262 Participants | 491 Participants |
| Sex: Female, Male Male | 737 Participants | 716 Participants | 1453 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 966 | 2 / 978 |
| other Total, other adverse events | 650 / 966 | 636 / 978 |
| serious Total, serious adverse events | 76 / 966 | 70 / 978 |
Outcome results
Primary
Depression Remission
The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. Remission was defined as a score of 5 or less at the endpoint. the reported number of participants are those reaching that threshold of symptoms.
Time frame: 24 weeks post randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Depression Remission | 130 Participants |
| Delay Results Group | Depression Remission | 126 Participants |
Primary
Use of Fewer Medications That Have Potential Gene-drug Interactions
The investigators will examine the proportion of antidepressants prescribed in the first 30 days of the trial that have the potential for gene-drug interactions. The chance for a gene-drug interaction was classified as 1. the subject did not have a prescription for an antidepressant during the initial 4 weeks of the trial (No Antidepressant), 2 the subject was prescribed an antidepressant with no known gene-drug interaction (No Gene Interaction), 3 the subject was prescribed an antidepressant with moderate gene-drug interactions (Moderate Interaction). These are also gene-drug interactions that do not have level A concordance. And 4. the subject was prescribed an antidepressant with substantial gene-drug interactions or gene-drug interactions that are considered to have a high level of evidence to support other prescribing.
Time frame: Over the first 30 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intervention Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | No Antidepressant prescibed | 239 Participants |
| Intervention Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with no gene interaction | 433 Participants |
| Intervention Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with moderate gene interaction | 215 Participants |
| Intervention Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with substantial gene interaction | 79 Participants |
| Delay Results Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with substantial gene interaction | 133 Participants |
| Delay Results Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | No Antidepressant prescibed | 299 Participants |
| Delay Results Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with moderate gene interaction | 373 Participants |
| Delay Results Group | Use of Fewer Medications That Have Potential Gene-drug Interactions | Taking an antidepressant with no gene interaction | 173 Participants |
Secondary
Depression Response
The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. Response was measured by a 50% reduction in scores from baseline to each time point.
Time frame: 24 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Group | Depression Response | 242 Participants |
| Delay Results Group | Depression Response | 216 Participants |
Secondary
Depression Severity
The investigators will use the Patient Health Questionnaire 9 (PHQ9) as a self-assessed marker of depression remission. The scale ranges from 0 to 27 with lower scores indicating less depression severity. This measure will use the PHQ9 as a continuous measure. The reported outcome is the difference in scores from baseline to 24 weeks.
Time frame: 24 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Depression Severity | 5.4 units on a scale | Standard Deviation 5.9 |
| Delay Results Group | Depression Severity | 4.8 units on a scale | Standard Deviation 5.6 |