Evaluation of an Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting

• ClinicalTrials.gov Identifier: NCT01610063
• Recruitment Status: Completed
• First Posted: June 1, 2012
• Results First Posted: March 30, 2017
• Last Update Posted: March 30, 2017
• Sponsor: Mayo Clinic
• Collaborator: Assurex Health Home
• Information provided by (Responsible Party): Daniel K. Hall-Flavin, Mayo Clinic

Study Description

Brief Summary:

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..

Condition or disease	Intervention/treatment	Phase
Depression	Other: Pharmacogenomic algorithm	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 227 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Pilot Study for the Evaluation of the Clinic-wide Impact of the Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting
• Actual Study Start Date: January 2009
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: May 2013

Arms and Interventions

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 Name: GeneSight
No Intervention: Unguided; Treatment as usual

Outcome Measures

Primary Outcome Measures :

1. Percentage Change in Quick Inventory of Depressive Symptomatology (QIDS-C16) Score From Baseline [ Time Frame: baseline, 8-week visit ]
   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.

Secondary Outcome Measures :

1. Percentage Change in Hamilton Depression Rating Scale (HAMD-17) Score From Baseline [ Time Frame: baseline, 8-week visit ]
   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.
2. Percentage Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline [ Time Frame: baseline, 8-week visit ]
   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.
3. Percentage Change in Outcome by Bin Status and Treatment Group [ Time Frame: baseline, 8-week visit ]
   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.
4. Pharmacogenomic Report Utilization [ Time Frame: baseline, 8-week visit ]
   Physicians were directed to complete a survey for each participant detailing their experiences during the study period.
5. Physicians' Perception of Participant's Satisfaction With Their Care [ Time Frame: 8-week visit ]
   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.
6. Responders at Week 8 [ Time Frame: baseline, 8 weeks ]
   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.
7. Remitters at Week 8 [ Time Frame: baseline, 8 weeks ]
   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).

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Wisconsin

Franciscan Skemp HealthCare

La Crosse, Wisconsin, United States, 54601

Sponsors and Collaborators

Mayo Clinic

Assurex Health Home

Investigators

• Principal Investigator: Daniel K. Hall-Flavin; Mayo Clinic

More Information

• Responsible Party: Daniel K. Hall-Flavin, PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01610063
• Other Study ID Numbers: 08-005610
• First Posted: June 1, 2012
• Results First Posted: March 30, 2017
• Last Update Posted: March 30, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel K. Hall-Flavin, Mayo Clinic:

Algorithm; Depression; Assurex; GeneSight

Additional relevant MeSH terms:

Depression; Behavioral Symptoms