PRIME Care (PRecision Medicine In MEntal Health Care)

Study Overview
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Brief Summary
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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
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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: 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) 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).

Official Title
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PRIME Care (PRecision Medicine In MEntal Health Care)

Conditions
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Major Depression

Intervention / Treatment
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* Other: Pharmacogenetic Test


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study intervention is the provision of pharmacogenetic test results which can then be used to choice appropriate medication.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Pharmacogenetic test results will be provided to the provider within 72 hours of randomization in order to facilitate choice in selecting antidepressants. | Other: Pharmacogenetic Test<br>* The intervention is a battery of pharmacogenetic test results that mostly affect the metabolism of antidepressants and other medications.<br>|
| No Intervention: Delay results group<br>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). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 weeks post randomization | 
| Use of fewer medications that have potential gene-drug interactions | The investigators will examine the proportion of antidepressants used that have the potential for gene-drug interactions. | Over the first 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antidepressant side effects | Self reported assessment of side effects related to antidepressants. Specific questions about nausea, headache, vomiting, GI distress, and sexual dysfunction. Each item rated as not present, mild, moderate, severe | over the 24 weeks | 
| VR -12 - Quality of life measure | The investigators will use the VR-12 as a self reported quality of life measure. | 24 weeks | 
| Antidepressant prescription availability | We will examine the availability of antidepressants by creating a possession ratio of the number of days that a prescription was filled and available to the Veteran. | 24 weeks | 
| 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. | 24 Weeks | 
| 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. Remission will be measured by a 50% reduction in scores from baseline to each time point. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment, Pharmacogenetics, Depression