Trial Outcomes & Findings for Evaluation of an Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting (NCT NCT01610063)

NCT ID: NCT01610063

Last Updated: 2017-03-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 227 participants
• Primary outcome timeframe: baseline, 8-week visit
• Results posted on: 2017-03-30

Participant Flow

This study was conducted at Franciscan Skemp Hospital in La Crosse, Wisconsin, a member of the Mayo Clinic Health System.

233 male and female patients between the ages of 18 and 80 years with a primary DSM-IV diagnosis of major depressive disorder or depressive disorder not otherwise specified (NOS) were approached for consent. 3 patients refused consent. 3 participants failed to meet eligibility criteria.

Participant milestones

Measure	Guided A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided Treatment as usual
Overall Study STARTED	114	113
Overall Study Baseline	114	113
Overall Study Completed 2-week	97	105
Overall Study Completed 4-week	86	98
Overall Study Completed 8-week	72	93
Overall Study COMPLETED	72	93
Overall Study NOT COMPLETED	42	20

Reasons for withdrawal

Measure	Guided A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided Treatment as usual
Overall Study Lost to Follow-up	42	20

Baseline Characteristics

Evaluation of an Antidepressant Pharmacogenomic Algorithm in an Outpatient Clinical Setting

Baseline characteristics by cohort

Measure	Guided n=114 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=113 Participants Treatment as usual	Total n=227 Participants Total of all reporting groups
Age, Continuous	41.0 years STANDARD_DEVIATION 12.8 • n=5 Participants	44.0 years STANDARD_DEVIATION 12.1 • n=7 Participants	42.62 years STANDARD_DEVIATION 12.55 • n=5 Participants
Sex: Female, Male Female	69 Participants n=5 Participants	77 Participants n=7 Participants	146 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	36 Participants n=7 Participants	81 Participants n=5 Participants
Region of Enrollment United States	114 participants n=5 Participants	113 participants n=7 Participants	227 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 8-week visit

Population: This analysis was performed on subjects who completed the study. There were 8 out of 72 patients in the guided arm and 12 out of 93 patients in the unguided arm who did not have assigned medication color in green/yellow/red. The number analyzed per row is indicated as (n=guided,unguided).

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.

Outcome measures

Measure	Guided n=72 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=93 Participants Treatment as usual
Percentage Change in Quick Inventory of Depressive Symptomatology (QIDS-C16) Score From Baseline Subjects in green/yellow category (n=48, 63)	-48.4 Percentage change in depression rating Standard Deviation 28.1	-31.8 Percentage change in depression rating Standard Deviation 29.8
Percentage Change in Quick Inventory of Depressive Symptomatology (QIDS-C16) Score From Baseline Subjects in red category (n=16, 18)	-41.2 Percentage change in depression rating Standard Deviation 31.7	-11.0 Percentage change in depression rating Standard Deviation 31.9

SECONDARY outcome

Timeframe: baseline, 8-week visit

Population: This analysis was performed on subjects who completed the study. There were 8 out of 72 patients in the guided arm and 12 out of 93 patients in the unguided arm who did not have assigned medication color in green/yellow/red. The number analyzed per row is indicated as (n=guided,unguided).

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.

Outcome measures

Measure	Guided n=72 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=93 Participants Treatment as usual
Percentage Change in Hamilton Depression Rating Scale (HAMD-17) Score From Baseline Subjects in red category (n=16, 18)	-42.2 Percentage change in depression rating Standard Deviation 24.8	-15.0 Percentage change in depression rating Standard Deviation 20.9
Percentage Change in Hamilton Depression Rating Scale (HAMD-17) Score From Baseline Subjects in green or yellow category (n=48, 63)	-49.5 Percentage change in depression rating Standard Deviation 28.4	-35.6 Percentage change in depression rating Standard Deviation 31.7

SECONDARY outcome

Timeframe: baseline, 8-week visit

Population: There were 8 out of 72 patients in the guided arm and 12 out of 93 patients in the unguided arm who did not have assigned medication color in green/yellow/red. The number analyzed per row is indicated as (n=guided,unguided). One subject in the guided arm (green/yellow) did not complete the PHQ-9 questionnaire at 8 weeks.

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.

Outcome measures

Measure	Guided n=72 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=93 Participants Treatment as usual
Percentage Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline Subjects in red category (n=16, 18)	-46.3 Percentage change in depression rating Standard Deviation 35.8	-15.5 Percentage change in depression rating Standard Deviation 31.4
Percentage Change in Patient Health Questionnaire-9 (PHQ-9) Score From Baseline Subjects in green/yellow category (n=47, 63)	-44.0 Percentage change in depression rating Standard Deviation 39.9	-20.7 Percentage change in depression rating Standard Deviation 63.9

SECONDARY outcome

Timeframe: baseline, 8-week visit

Population: All subjects were evaluated for a bin status, but not all the arms had subjects assigned to every bin status (green, yellow, or red). Bin status for each category title is reported as (n=Guided, Unguided).

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.

Outcome measures

Measure	Guided n=72 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=93 Participants Treatment as usual
Percentage Change in Outcome by Bin Status and Treatment Group %Change in PHQ-9 score, red (n=16,18)	-46.3 Percentage change Standard Deviation 35.8	-15.5 Percentage change Standard Deviation 31.4
Percentage Change in Outcome by Bin Status and Treatment Group %Change in PHQ-9 score, green/yellow (n=47,63)	-44.0 Percentage change Standard Deviation 39.9	-20.7 Percentage change Standard Deviation 63.9
Percentage Change in Outcome by Bin Status and Treatment Group %Change in HAMD-17 score, red (n=16, 18)	-42.2 Percentage change Standard Deviation 24.8	-15.0 Percentage change Standard Deviation 20.9
Percentage Change in Outcome by Bin Status and Treatment Group %Change in HAMD-17 score, green/yellow (n=48,63)	-49.5 Percentage change Standard Deviation 28.4	-35.6 Percentage change Standard Deviation 31.7
Percentage Change in Outcome by Bin Status and Treatment Group %Change in QIDS-C16 score, red (n=16,18)	-41.2 Percentage change Standard Deviation 31.7	-11 Percentage change Standard Deviation 31.9
Percentage Change in Outcome by Bin Status and Treatment Group %Change in QIDS-C16 score green/yellow (n=48,63)	-48.4 Percentage change Standard Deviation 28.1	-31.8 Percentage change Standard Deviation 29.8

SECONDARY outcome

Timeframe: baseline, 8-week visit

Population: The medication changes of patients were recorded only for patients who completed the 8-week study (n=72,93 for guided and unguided arms). For each row below, the number of subjects analyzed is indicated by (n=guided, unguided) arms.

Physicians were directed to complete a survey for each participant detailing their experiences during the study period.

Outcome measures

Measure	Guided n=72 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=93 Participants Treatment as usual
Pharmacogenomic Report Utilization Overall med/dose changes (n=72, 93)	76.8 percentage of participants	44.1 percentage of participants
Pharmacogenomic Report Utilization Med/dose changes in red bin subjects (n=16, 18)	93.8 percentage of participants	55.6 percentage of participants

SECONDARY outcome

Timeframe: 8-week visit

Population: Physicians completed surveys for 89 participants (96%) from the unguided group, and for 37 participants (51.4%) from the guided group. For each row below, the number of subjects analyzed is indicated by (n=guided, unguided) arms. For the first row, one of the physicians who completed the survey did not answer this question.

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.

Outcome measures

Measure	Guided n=37 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=89 Participants Treatment as usual
Physicians' Perception of Participant's Satisfaction With Their Care Physicians satisfied with care (n=37,89)	94.6 percentage of physicians	61.8 percentage of physicians
Physicians' Perception of Participant's Satisfaction With Their Care Very confident/confident med selection (n=37,89)	91.9 percentage of physicians	61.8 percentage of physicians
Physicians' Perception of Participant's Satisfaction With Their Care Very high patient satisfaction (n=37,88)	40.5 percentage of physicians	14.8 percentage of physicians

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Guided n=114 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=113 Participants Treatment as usual
Responders at Week 8 HAMD-17	43.1 percentage of participants	26.9 percentage of participants
Responders at Week 8 PHQ-9	50.7 percentage of participants	31.2 percentage of participants
Responders at Week 8 QIDS-C16	44.4 percentage of participants	23.7 percentage of participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Guided n=114 Participants A pharmacogenomic algorithm (GeneSight) guided treatment decisions for antidepressant medication selection and appropriate dosing.	Unguided n=113 Participants Treatment as usual
Remitters at Week 8 QIDS-C16	26.4 percentage of participants	12.9 percentage of participants
Remitters at Week 8 HAMD-17	30.6 percentage of participants	21.5 percentage of participants
Remitters at Week 8 PHQ-9	25.4 percentage of participants	16.1 percentage of participants

Adverse Events

Guided

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Unguided

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Daniel K. Hall-Flavin

Mayo Clinic

Phone: 507-255-4151

Email: flavin.daniel@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place