Clinical Impact of the Antidepressant Pharmacogenomic Algorithm in an Outpatient Therapy-based Clinical Setting

Study Overview
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Brief Summary
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The Mayo Clinic psychiatric pharmacogenomic team has developed a pharmacogenomic algorithm that has been designed to improve the effectiveness and safety of antidepressant medications by providing guidance in medication selection and appropriate dosing. This algorithm has been incorporated into a new genotyping interpretative report. This report is now available from AssureRx. The pharmacogenomic algorithm is based on genotyping both copies of four informative genes. These four genes are: 1) the Cytochrome P450 2D6 gene; 2) the Cytochrome P450 2C19 gene; 3) the Serotonin Transporter gene (SLC6A4); and 4) the Serotonin 2A receptor gene (5HTR2A). Though this algorithm is not yet part of the universal standard of care, Mayo clinicians have found it helpful in guiding treatment decisions at Mayo Clinic Rochester.

Detailed Description
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The proposed pilot study is designed to evaluate the clinical impact of the interpretive report in an outpatient behavioral health clinic in St. Paul, Minnesota. While the ultimate goal of this project is to show an improvement in patient outcomes, this pilot study will be used to evaluate the feasibility of introducing the pharmacogenomic algorithm to a new setting that does not routinely use the algorithm. Secondary outcome data will be collected to generate meaningful estimates of the magnitude of potential treatment effects. The study will consist of two phases, each enrolling 2530 subjects. In Phase 1, consecutive patients will be prospectively monitored to observe standard practice. Patients will be given the option to receive genotyping and those that agree will have blood drawn. However, the results of the genotyping and algorithm will not be released until all phase 1 patients have completed study visits.. Subsequently, in Phase 2, also enrolling 3025 subjects, the results of the genotyping and algorithm will be made available immediately for additional consecutive prospectively monitored patients. Patients will be prospectively monitored in the same fashion as Phase 1. The results of the study will be used to perform preliminary analyses and subsequent fully powered multi-site trials will be planned based on the results of this study.

Official Title
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A Pilot Study for the Evaluation of the Clinical Impact of the Antidepressant Pharmacogenomic Algorithm in an Outpatient Therapy-based Clinical Setting

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Genetic: Genotyping results


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is between the ages of 18 and 80. Major depressive disorder or depressive disorder not otherwise specified (NOS) as ascertained by a physician or mental health professional licensed to diagnose. Patient is an outpatient and not in imminent need of inpatient hospitalization Patient's Hamilton Depression Rating score is >14 Patient is being seen by a psychiatrist for optimum medication management. Ability to read, understand and sign an informed consent document Exclusion Criteria: Serious medical illness (as ascertained via the initial triage screening process) Patients with a diagnosis of Bipolar I disorder Patients with a diagnosis of Schizophrenia or Schizoaffective disorder Patients who are legally unable to consent to enrollment in the study (i.e. patients with legal guardians)

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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Part 1<br>This is the treatment as usual arm to monitor the current standard clinical practice | |
| Other: Part 2<br>This group will be provided with genotyping results after baseline visit to guide clinical medication management | Genetic: Genotyping results<br>* Genotyping results provided in Phase II<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients approached who consent to use of pharmacogenomic algorithm |  | 8 weeks | 
| Amount of time from ordering test to receipt of results |  | 8 weeks | 
| Proportion of time that the physician prescribed a medication that was recommended by the algorithm |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to remission of depressive symptoms | Hamilton rating of < 7 | 8 weeks | 
| Measured side effect burden | Reduction in Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) score. | 8 weeks | 
| Number of participants who change their initial medication regimen |  | 8 weeks | 
| Health care clinical cost | defined by analysis of mental health resource utilization | 8 weeks | 
| Physician satisfaction with delivery of clinical care | defined by researcher developed Likert-based satisfaction survey | 8 weeks | 
| Patient satisfaction with clinical care | defined by researcher developed Likert-based satisfaction survey | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AssureRx, Algorithm, Major depressive disorder