Trial Outcomes & Findings for A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Depression Trial) (NCT NCT05966155)

Last Updated: 2025-06-29

Results Overview

The 8-item PROMIS Emotional Distress Depression 8b and PROMIS Pediatric Depression Symptoms 8a questionnaire assess the extent to which participants experience depression symptoms over the past 7 days using a 5-point Likert scale. The responses to the 8 questions are converted to T-scores using the health measures assessment center scoring service. Pediatric T-scores are cross walked to adult T-scores using the cross walk published in Reeve et al 2016. Cross walked T-scores range from 37.1 to 80.9, higher scores correspond with higher levels of depression symptoms. Changes in T-scores from baseline to 3-months range from -43.8 to 43.8. Negative values of change in T-score correspond to symptom improvement, 0 corresponds to no change in depression T-scores, and positive change in depression T-scores correspond to symptom worsening at 3 months compared to baseline.

Recruitment status

COMPLETED

Study phase

Target enrollment

1572 participants

Primary outcome timeframe

Baseline to 3 months

Results posted on

2025-06-29

Participant Flow

This record is specific to the Depression Trial within the ADOPT PGx protocol. It only contains the participants consented to the Depression Trial.

There were 1572 participants consented into the Depression trial. 112 consented participants were not randomized into the trial and were not assigned to a treatment arm. The 1460 randomized participants will be described moving forward.

Participant milestones

Participant milestones
Measure	Depression - Immediate PGx Testing Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results	Depression - Delayed PGx Testing Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Overall Study STARTED	727	733
Overall Study COMPLETED	654	653
Overall Study NOT COMPLETED	73	80

Reasons for withdrawal

Reasons for withdrawal
Measure	Depression - Immediate PGx Testing Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19 Clinical decisions support: Prescribing recommendations to the provider based on the pharmacogenetic testing results	Depression - Delayed PGx Testing Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period Pharmacogenetic testing: Genetic testing of CYP2D6 and CYP2C19
Overall Study Death	1	2
Overall Study Lost to Follow-up	63	67
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	8	9
Overall Study Enrolled Erroneously	0	1
Overall Study Follow-up Incorrectly Scheduled	0	1

Baseline Characteristics

Intent to Treat Population

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline to 3 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed PROMIS Depression surveys at both baseline and 3 months are included. Participants with missing PROMIS depression surveys at either baseline or 3-months are excluded.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=329 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=320 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	-4.3 T-score Standard Deviation 8.4	-4.0 T-score Standard Deviation 8.1

SECONDARY outcome

Timeframe: Baseline to 3 months

Population: Modified ITT population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed PHQ-8 surveys at both baseline and 3 months are included. Participants with missing PHQ-8 surveys at either baseline or 3-months are excluded.

The 8-item PHQ-8 Questionnaire assesses severity of depression over the past 2 weeks using a 4-point scale indicating frequency of depression symptoms: not at all, several days, more than half the days, or nearly every day. The 8 questions are converted to a score ranging from 0 (not at all for all 8 symptoms) to 24 (nearly every day for all 8 symptoms). Changes in PHQ-8 scores from baseline to 3-months range from -24 to 24 and negative values of change in PHQ-8 correspond to improvement in depression at 3 months compared to baseline.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=327 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=320 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8)	-3.3 score on a scale Standard Deviation 5.2	-2.7 score on a scale Standard Deviation 4.8

SECONDARY outcome

Timeframe: 3 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with completed medication side effect surveys at 3 months are included. Participants with missing side effect surveys at 3-months are excluded.

An 8-item survey was developed to assess the severity of 8 depression medication side effects, using a 4-point scale for rating severity of the side effect: none, mild, moderate, severe. The 8 questions are converted to a side effect burden score ranging from 0 (none for all 8 side effects) to 24 (severe for all 8 side effects). Higher values correspond with more side effects and with higher severity.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=285 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=283 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Side Effect Burden	8.2 score on a scale Standard Deviation 4.3	7.8 score on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: 3 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with 2 or more Voils survey questions completed at 3 months are included. Participants with fewer than 2 completed Voils survey questions are excluded.

Medication adherence level, non-adherent / adherent, derived from the Voils Medication Adherence survey. Reported as the number of participants who were non-adherent.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=323 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=317 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Medication Non-Adherence as Measured by the Voils Medication Adherence Survey	142 Participants	137 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PROMIS depression survey at 6 months are include. Participants with an incomplete PROMIS depression survey are excluded.

Remission is defined as whether or not the summed raw responses to the PROMIS emotional distress depression survey is ≤ 16, corresponding to a participant respond "rarely" or "never" to most or all questions.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=317 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=310 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	153 Participants	122 Participants

SECONDARY outcome

Timeframe: 6 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PHQ-8 survey at 6 months are include. Participants with an incomplete PHQ-8 survey are excluded.

The PHQ-8 scores range from 0 to 24 and remission is defined as having a PHQ-8 score of ≤ 4.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=318 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=309 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8)	95 Participants	65 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed PHQ-8 survey at baseline and 3 months are included. Participants with an incomplete PHQ-8 survey at either baseline or 3 months are excluded.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=327 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=321 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score	92 Participants	71 Participants

SECONDARY outcome

Timeframe: 3 months

Population: Modified intent to treat (mITT) population consisting of participants with a CYP2C19 poor, rapid, or ultra-rapid metabolizer phenotype or a CYP2D6 poor or ultra-rapid metabolizer phenotype. All mITT participants with a completed medication review at 3 months are included. Participants without a medication review at 3 months are excluded.

Concordance defined as agreement between the PGx phenotype and SSRI medications reported.

Outcome measures

Outcome measures
Measure	Depression - Immediate PGx Testing (Modified Intent to Treat, mITT) n=323 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing (Modified Intent to Treat, mITT) n=315 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period
Number of Participants With Drug-gene Concordance	273 Participants	234 Participants

Adverse Events

Depression - Immediate PGx Testing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Depression - Delayed PGx Testing

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Hrishikesh Chakraborty, PhD

Duke University

Phone: 919-668-1238

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Depression - Immediate PGx Testing n=727 Participants Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Depression - Delayed PGx Testing n=733 Participants Delayed genetic testing of CYP2D6 and CYP2C19 and return of results after the conclusion of the 6-month follow-up period	Total n=1460 Participants Total of all reporting groups
Age, Categorical <=18 years	49 Participants n=351 Participants • Modified Intent to Treat Population	48 Participants n=341 Participants • Modified Intent to Treat Population	97 Participants n=692 Participants • Modified Intent to Treat Population
Age, Categorical Between 18 and 65 years	273 Participants n=351 Participants • Modified Intent to Treat Population	255 Participants n=341 Participants • Modified Intent to Treat Population	528 Participants n=692 Participants • Modified Intent to Treat Population
Age, Categorical >=65 years	29 Participants n=351 Participants • Modified Intent to Treat Population	38 Participants n=341 Participants • Modified Intent to Treat Population	67 Participants n=692 Participants • Modified Intent to Treat Population
Sex: Female, Male Female	266 Participants n=351 Participants • Modified Intent to Treat Population	248 Participants n=341 Participants • Modified Intent to Treat Population	514 Participants n=692 Participants • Modified Intent to Treat Population
Sex: Female, Male Male	85 Participants n=351 Participants • Modified Intent to Treat Population	93 Participants n=341 Participants • Modified Intent to Treat Population	178 Participants n=692 Participants • Modified Intent to Treat Population
Ethnicity (NIH/OMB) Hispanic or Latino	38 Participants n=351 Participants • Modified Intent to Treat Population	54 Participants n=341 Participants • Modified Intent to Treat Population	92 Participants n=692 Participants • Modified Intent to Treat Population
Ethnicity (NIH/OMB) Not Hispanic or Latino	311 Participants n=351 Participants • Modified Intent to Treat Population	285 Participants n=341 Participants • Modified Intent to Treat Population	596 Participants n=692 Participants • Modified Intent to Treat Population
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=351 Participants • Modified Intent to Treat Population	2 Participants n=341 Participants • Modified Intent to Treat Population	4 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=351 Participants • Modified Intent to Treat Population	2 Participants n=341 Participants • Modified Intent to Treat Population	4 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) Asian	5 Participants n=351 Participants • Modified Intent to Treat Population	10 Participants n=341 Participants • Modified Intent to Treat Population	15 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=351 Participants • Modified Intent to Treat Population	0 Participants n=341 Participants • Modified Intent to Treat Population	1 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) Black or African American	60 Participants n=351 Participants • Modified Intent to Treat Population	52 Participants n=341 Participants • Modified Intent to Treat Population	112 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) White	235 Participants n=351 Participants • Modified Intent to Treat Population	228 Participants n=341 Participants • Modified Intent to Treat Population	463 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) More than one race	16 Participants n=351 Participants • Modified Intent to Treat Population	15 Participants n=341 Participants • Modified Intent to Treat Population	31 Participants n=692 Participants • Modified Intent to Treat Population
Race (NIH/OMB) Unknown or Not Reported	32 Participants n=351 Participants • Modified Intent to Treat Population	34 Participants n=341 Participants • Modified Intent to Treat Population	66 Participants n=692 Participants • Modified Intent to Treat Population
Region of Enrollment United States	727 Participants n=727 Participants	733 Participants n=733 Participants	1460 Participants n=1460 Participants