Evaluation of an Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting

A Pilot Study for the Evaluation of the Clinic-wide Impact of the Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting

This was a study of a genotyping tool that reported on how subjects responded to medications and could be used in a community psychiatry practice to improve medication choice for depression. After the DNA test, an interpretive report was provided to the subjects' physicians. The hypothesis of this pilot study was that it was feasible to use this pharmacogenomic algorithm in a new setting to treat depressed subjects..

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Other: Pharmacogenomic algorithm

Detailed Description

Antidepressant medications are among the most widely prescribed medications. However, only 35% to 45% of depressed patients have a complete remission of their illness when initially treated with these medications. Consequently, the Mayo Clinic psychiatric pharmacogenomic team developed a pharmacogenomic algorithm 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. 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). The trial took place at the Franciscan Skemp Healthcare System in La Crosse, Wisconsin over the course of 12 months.

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is between the ages of 18 and 80.
2. Major depressive disorder or depressive disorder not otherwise specified as ascertained by a physician or mental health professional licensed to diagnose.
3. Patient is an outpatient and not in imminent need of inpatient hospitalization, or a discharging inpatient with scheduled follow-up with a Behavioral Health psychiatrist.
4. Patient has been referred to see a psychiatrist for optimum medication management.
5. Patient's Hamilton Depression Rating score is >14
6. Ability to read, understand and sign an informed consent document

Exclusion Criteria:

1. Serious medical illness (as ascertained via the initial triage screening process)
2. Patients with a diagnosis of Bipolar I disorder
3. Patients with a diagnosis of Schizophrenia or Schizoaffective disorder
4. Patients who are legally unable to consent to enrollment in the study (i.e. patients with legal guardians)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Guided; A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Other: Pharmacogenomic algorithm; Genetic test results for 4 genes were put through algorithm and provided to physician for guidance prescribing medication.; Other Names: GeneSight
No Intervention: Unguided; Treatment as usual

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Quick Inventory of Depressive Symptomatology (QIDS-C16) Score From Baseline	The QIDS-C16 is a 16-item scale that is clinician-rated; it is designed to assess the severity of depressive symptoms. The QIDS-C16 total score ranges from 0-27. Scores ranging from 0 to 10 correspond with no to mild depression, while scores >/= 11 correspond to moderate to severe depression. A negative change indicates improvement in the subject's depression, and a positive change indicates a worsening of the subject's depression.	baseline, 8-week visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Hamilton Depression Rating Scale (HAMD-17) Score From Baseline	The HAMD-17 is a 17-item scale that evaluates depressed mood, vegetative and cognitive symptoms of depression, and co-morbid anxiety symptoms. The 17 items are rated on either a 5-point (0-4) or a 3-point (0-2) scale. In general, the 5 point scale items use a rating of 0=absent; 1=doubtful to mild; 2=mild to moderate; 3=moderate to severe; 4=very severe. The 3-point scale items use a rating of 0=absent; 1=probable or mild; 2=definite. The total HAMD-17 score ranges from 0 (not ill) to 52 (severely ill). A negative change indicates improvement in the subject's depression/anxiety symptoms, and a positive change indicates a worsening of the subject's depression/anxiety symptoms.	baseline, 8-week visit
Percentage Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline	The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is based directly on the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual Fourth Edition (DSM-IV). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 27 (severe symptoms) for depression. A negative change indicates improvement in the subject's depression symptoms, and a positive change indicates a worsening of the subject's depression symptoms.	baseline, 8-week visit
Percentage Change in Outcome by Bin Status and Treatment Group	The Genesight algorithm presents recommendations for antidepressants and antipsychotics in "bin status" associated with colors. Green indicates "Use as Directed." Yellow indicates "Use with Caution." Red indicates "Use with Increased Caution and with More Frequent Monitoring." Definitions of the depression questionnaires are found in previous outcome measures. A negative change indicates improvement in the subject's depression/anxiety symptoms, and a positive change indicates a worsening of the subject's depression/anxiety symptoms.	baseline, 8-week visit
Pharmacogenomic Report Utilization	Physicians were directed to complete a survey for each participant detailing their experiences during the study period.	baseline, 8-week visit
Physicians' Perception of Participant's Satisfaction With Their Care	Physicians reported on their perception of each participant's satisfaction with their care only for patients who completed the 8-week study. Physicians were directed to complete a survey for each participant detaining their experience during the study period.	8-week visit
Responders at Week 8	Definitions of the depression questionnaires are found in previous outcome measures. Definition of responder: a participant who had 50% or higher reduction in psychiatric score from baseline.	baseline, 8 weeks
Remitters at Week 8	Definitions of the depression questionnaires are found in previous outcome measures. Definition of remitter: a participant with score less than or equal to certain value (HAMD-17 <=7, QIDS-C16<=5, PHQ-9<5).	baseline, 8 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Assurex Health Home
• Investigators: Principal Investigator: Daniel K. Hall-Flavin, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: May 25, 2012
• First Submitted That Met QC Criteria: May 30, 2012
• First Posted (Estimate): June 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: February 10, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Depression; GeneSight; Assurex; Algorithm
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 08-005610

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No