A Depression and Opioid Pragmatic Trial in Pharmacogenetics (Depression Trial) (ADOPT PGx)

A Depression and Opioid Pragmatic Trial in Pharmacogenetics

This study is comprised of three separate pharmacogenetic trials grouped into a single protocol due to similarities in the intervention, the hypotheses, and the trial design. The three trials are the Acute Pain Trial, the Chronic Pain Trial, and the Depression Trial. Participants can enroll in only one of the three trials. All three trials were registered on ClinicalTrials.gov under NCT04445792. In July 2023 each of the three treatment trials was registered under a separate NCT# and NCT04445792 was converted to a screening record per recent guidance on master protocol research programs (MPRPs). This record is specific to the Depression Trial within the ADOPT-PGx protocol.

The Depression Trial is a prospective, multicenter, two arm randomized pragmatic trial. Participants meeting eligibility criteria will be randomly assigned to either immediate pharmacogenetic testing and genotype-guided anti-depressant therapy (Intervention arm) or standard care with 6-month delayed pharmacogenetic testing (Control arm). The investigators will test the hypothesis that pharmacogenetic testing and genotype-guided anti-depressant therapy will reduce depression symptoms in participants who's body processes some anti-depressants faster or slower than normal.

Study Overview

• Status: Completed
• Conditions: Depression
• Intervention / Treatment: Other: Pharmacogenetic testing; Other: Clinical decisions support

Detailed Description

Pain and depression are conditions that impact substantial proportions of the US population. Finding safe and effective drug therapies for both conditions is challenging. In the case of treatment for acute and chronic pain, the challenge is finding effective therapy while minimizing adverse effects or opioid addiction (and the ensuing consequences). For depression, there are few clinically relevant predictors of successful treatment leading to multiple trials of inadequate therapy for some patients. Both opioid and antidepressant prescriptions can be guided by pharmacogenetics (PGx) data based on existing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC).

This study is designed to evaluate the impact of pharmacogenetic testing and genotype-guided pain or anti-depressant therapy on pain control or depression symptoms in a pragmatic setting.

The rationale for examining a genotype-guided approach to acute and chronic pain management is based on the importance of CYP2D6 for the bioactivation of tramadol, codeine, and hydrocodone and data from a pilot study supporting improved pain control in intermediate and poor CYP2D6 metabolizers in the genotype-guided arm who are taking these drugs at baseline. Similarly, the rationale for examining a genotype-guided approach to depression medication therapy is based on the demonstrated role of CYP2D6 in the bio inactivation and CYP2C19 oxidation of select, commonly used SSRIs. Secondly, data from industry sponsored trials support the hypothesis of improved depression symptom control in a genotype-guided arm.

Study objectives:

Determine if genotype-guided dosing or selection of antidepressants among participants with at least 3 months of depressive symptoms who require new or revised antidepressant therapy leads to improved control of depression, compared to usual care.

• Study Type: Interventional
• Enrollment (Actual): 1572
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours Children's Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainesville
    • Jacksonville, Florida, United States, 32209
      • University of Florida - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System
    • Orlando, Florida, United States, 32827
      • Nemours Children's Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Health
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10035
      • The Institute for Family Health
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Sanford Health
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College
    • Nashville, Tennessee, United States, 37208
      • Nashville General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Depression Trial

• Age ≥ 8 years
• English speaking or Spanish speaking
• Patients followed at psychiatry clinics or primary care clinics at an enrolling site (such as, but not limited to, Internal Medicine, Family Medicine, or Pediatrics)
• Documentation of depression and/or provider report of depression
• Evidence of depressive symptoms for at least 3 months based on patient interview or documentation in electronic health records
• Recent initiation of SSRI therapy, recent revised SSRI therapy, or anticipated need for revised or new SSRI therapy per health care provider

Exclusion Criteria

Trial-wide:

• Life expectancy less than 12 months
• Are too cognitively impaired to provide informed consent and/or complete study protocol
• Are institutionalized or too ill to participate (i.e. mental or nursing home facility or incarcerated)
• Have a history of allogeneic stem cell transplant or liver transplant
• People with prior clinical pharmacogenetic test results for genes relevant for the study in which they will enroll (CYP2D6 for the pain studies and CYP2D6 or CYP2C19 for depression) or already enrolled in an ADOPT PGx trial

Depression Trial

• Plan to move out of the area within 6 months of enrollment
• Have active psychosis or diagnosed psychotic disorders (schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, substance induced psychosis, schizophreniform disorder)
• Have dementia or other neurocognitive disorders due to any cause, such as Alzheimer's disease, vascular/subcortical, lewy body disease, frontotemporal lobar degeneration
• Have cognitive developmental delay and/or cognitive disability, including autism spectrum disorders (Note: ADHD is not an exclusion criteria)
• Has a seizure disorder
• Have bipolar disorder

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depression - Immediate PGx Testing; Immediate genetic testing of CYP2D6 and CYP2C19 and clinical decisions support for antidepressant prescribing to the healthcare provider	Other: Pharmacogenetic testing; Genetic testing of CYP2D6 and CYP2C19; Other: Clinical decisions support; Prescribing recommendations to the provider based on the pharmacogenetic testing results
Other: 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	Other: Pharmacogenetic testing; Genetic testing of CYP2D6 and CYP2C19

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Symptom Control as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	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.	Baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Symptomatology as Measured by Patient Health Questionnaire (PHQ-8)	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.	Baseline to 3 months
Side Effect Burden	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.	3 months
Medication Non-Adherence as Measured by the Voils Medication Adherence Survey	Medication adherence level, non-adherent / adherent, derived from the Voils Medication Adherence survey. Reported as the number of participants who were non-adherent.	3 months
Number of Participants With Depression Remission as Measured by PROMIS (Patient-Reported Outcomes Measurement Information System)	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.	6 months
Number of Participants With Depression Remission as Measured by the Patient Health Questionnaire (PHQ-8)	The PHQ-8 scores range from 0 to 24 and remission is defined as having a PHQ-8 score of ≤ 4.	6 months
Number of Participants With 50% Reduction in Patient Health Questionnaire (PHQ-8) Score		3 months
Number of Participants With Drug-gene Concordance	Concordance defined as agreement between the PGx phenotype and SSRI medications reported.	3 months

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Icahn School of Medicine at Mount Sinai; University of Florida; Vanderbilt University Medical Center; National Human Genome Research Institute (NHGRI); Indiana University School of Medicine
• Investigators: Study Director: Hrishikesh Chakraborty, Duke University; Principal Investigator: Josh F. Peterson, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Hines LJ, Wilke RA, Myers R, Mathews CA, Liu M, Baye JF, Petry N, Cicali EJ, Duong BQ, Elwood E, Hulvershorn L, Nguyen K, Ramos M, Sadeghpour A, Wu RR, Williamson L, Wiisanen K, Voora D, Singh R, Blake KV, Murrough JW, Volpi S, Ginsburg GS, Horowitz CR, Orlando L, Chakraborty H, Dexter P, Johnson JA, Skaar TC, Cavallari LH, Van Driest SL, Peterson JF; IGNITE Pragmatic Trials Network. Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression. Clin Transl Sci. 2024 Jun;17(6):e13822. doi: 10.1111/cts.13822.

Helpful Links

• Rationale and design for a pragmatic randomized trial to assess gene-based prescribing for SSRIs in the treatment of depression

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): April 27, 2024
• Study Completion (Actual): April 27, 2024

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: July 21, 2023
• First Posted (Actual): July 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 29, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: CYP2D6; CYP2C19; Pharmacogenetic
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: PRO00104948_C; U01HG010225 (U.S. NIH Grant/Contract)

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