Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents With Anxiety and Depression (PGx-GAP)

This is a parallel arm randomized (1:1) controlled trial. Adolescents aged 12-17 years (n=452) who are starting or changing a selective serotonin reuptake inhibitor (SSRI) for depression and/or anxiety will be randomly allocated to receive 12-weeks of pharmacogenetic-guided antidepressant therapy (experimental intervention) or current prescribing guidelines/recommendations guided therapy (control intervention).

Study Overview

• Status: Recruiting
• Conditions: Anxiety and Depression
• Intervention / Treatment: Other: Pharmacogenetic-guided dosing; Other: Current prescribing guidelines/recommendations

Detailed Description

Goal: To test the efficacy of pharmacogenetic-guided antidepressant prescribing for adolescents with depression.

Background: For an adolescent with depression and anxiety, antidepressant medication is prescribed, often in combination with psychotherapy. The class of antidepressants recommended for use is selective serotonin reuptake inhibitors (SSRIs) with fluoxetine recommended as the first-line medication, and four other SSRIs recommended for consideration (sertraline, citalopram, escitalopram, fluvoxamine) if the adolescent does not respond or tolerate fluoxetine. For most adolescents, medication prescribing, and monitoring will be managed by a primary care physician or community pediatrician rather than by a mental health care provider, and guidelines exist to support this management. However, current prescribing guidelines/recommendations do not account for SSRI metabolism phenotypes that could change whether the SSRI selected is efficacious or tolerated. Our team of researchers, clinician scientists, patient partners, and primary care providers has designed a trial to test the impact of accounting for metabolism phenotypes, through pharmacogenetic-guided antidepressant prescribing, on adolescent outcomes, experiences, and health care utilization.

Principal Question: Compared to current prescribing guideline/recommendation informed prescribing, does pharmacogenetic-guided prescribing for adolescents with depression and/or anxiety have superior efficacy following 12-weeks of therapy with a SSRI?

The Trial: This is a parallel arm randomized controlled trial. Adolescents aged 12-17 years (n=452) who are starting or changing a SSRI for depression and/or anxiety will be randomly allocated to receive pharmacogenetic-guided antidepressant therapy (experimental intervention) or current prescribing guideline/recommendation guided prescribing (control intervention). Participants and prescribing physicians will be blinded to which intervention was received. The primary outcome is depressive symptom remission at 12 weeks measured using the Quick Inventory of Depressive Symptomatology - Adolescent (17-item) (QIDS-A17) and anxiety symptom remission at 12 weeks measures using the Screen for Child Anxiety Related Disorders (SCARED). Secondary outcomes include side effects, role functioning, medication adherence, and health-related quality of life measured 4-, 8-, and 12-weeks after intervention initiation as well as cost-effectiveness.

• Study Type: Interventional
• Enrollment (Estimated): 452
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Meagan Shields, BSc., MSc.; Phone Number: 403-210-6353; Email: gap@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • Recruiting
      • University of Calgary
      • Principal Investigator: Chad Bousman, PhD
      • Contact: Meagan Shields, BSc., MSc.; Phone Number: 403-210-6353; Email: gap@ucalgary.ca
      • Principal Investigator: Amanda Newton, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 12-17
• Depression and/or anxiety as the primary concern, confirmed by the treating physician
• Intention to start a new SSRI
• English fluency

Exclusion Criteria:

• Co-occurring obsessive compulsive disorder, psychosis, bipolar disorder, eating disorder, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability
• History of non-response to 3 or more SSRI medications as confirmed by the treating physician
• Brain stimulation-based therapy initiated within 8 weeks of referral, or plans to initiate/change brain stimulation during study participation
• History of liver or hematopoietic cell transplant
• History of CYP2B6, CYP2C19, or CYP2D6 testing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Pharmacogenetic (PGx)-Guided; Participants and their physician will receive a one-time prescribing report after completing baseline for selective serotonin reuptake inhibitors with dosing information based on CYP2B6, CYP2C19, and CYP2D6 genotype data, and clinical practice guidelines for fluoxetine as there are no pharmacogenetic guidelines for this medication.	Other: Pharmacogenetic-guided dosing; SSRI dosing based on Clinical Pharmacogenetics Implementation Consortium's SSRI dosing guidelines.
Active Comparator: Current Prescribing Guidelines/Recommendations; Participants and their physician will receive a one-time prescribing report after completing baseline for selective serotonin reuptake inhibitors based on current prescribing guidelines/recommendations.	Other: Current prescribing guidelines/recommendations; SSRI dosing based on current prescribing guidelines/recommendations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with depression remission	Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17) total score < 6. Scores range from 0-27, with higher scores indicative of more severe depression.	Baseline to 12 weeks
Number of participants with anxiety remission	Screen for Child Anxiety Related Disorders (SCARED) total score < 25. Scores range from 0-82, with higher scores indicative of more severe anxiety.	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with side effects and adverse drug reactions	Frequency, Intensity, Burden of Side Effects Rating (FIBSER) scale. Total scores range from 0-6 (3 items); cut-points are used to indicate moderate (score of 3) or severe (score of 5) adverse drug reaction/side effect interference with activities.	Baseline to 12 weeks
Change in self-report health care resource use	Resource use questionnaire that captures number of visits and out-of-pocket costs for various mental health services.	Baseline to 12 weeks
Change in health-related quality of life	EuroQoL 5 Dimension - Youth (EQ-5D-Y). Five descriptive items code level of perceived problems in health states and a visual analog scale has a score from 0-100, with higher scores indicative of better health.	Baseline to 12 weeks
Change in medication adherence	Medication Adherence Report Scale (MARS-5) scores. Scores range from 5-25 with higher scores indicative of better medication adherence.	4 to 12 weeks
Change in behavioral activation	Emergence of activation based on Treatment-Emergent Activation and Suicidality Assessment Profile. Total scores range from 0-114 (38 items) with higher scores indicating greater behavioral activation.	Baseline to 12 weeks
Percent change in role functioning	WHO Disability Assessment Schedule. Scores range from 0 to 48, with higher scores indicative of worse role functioning.	Baseline to 12 weeks
Percent change in depressive symptom severity	Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17). Scores range from 0-27, with higher scores indicative of more severe depression.	Baseline to 12 weeks
Percent change in anxiety symptom severity	Screen for Child Anxiety Related Disorders (SCARED) total score < 25. Scores range from 0-82, with higher scores indicative of more severe anxiety.	Baseline to 12 weeks
Percent change in clinician assessment of depressive and anxiety symptom severity	Change in Clinical Global Impression Severity (CGI-S) scale. Scores range from 0-7, with higher scores indicative of more severe illness.	Baseline to 12 weeks
Change in healthcare utilization - physician visits	Administrative data will be obtained on change in number of physician visits.	Baseline to 12 weeks
Change in health care utilization - emergency department visits	Administrative data will be obtained on change in number of emergency department visits.	Baseline to 12 weeks
Change in health care utilization - hospitalizations	Administrative data will be obtained on change in number of hospitalizations.	Baseline to 12 weeks
Change in prescribed medication dose	Administrative data will be obtained on changes to prescribed medication doses.	Baseline to 12 weeks
Change in prescribed agent	Administrative data will be obtained on changes of agent for prescribed medications.	Baseline to 12 weeks
Change in prescribed medication duration	Administrative data will be obtained on duration of use of prescribed medications.	Baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimally clinically important differences	Participant-reported, Global Rating of Change Scale (GRCS) (11-point Likert scale ranging from +5 to -5) to indicate the degree to which symptoms and role functioning changed for the better, for the worse, or no change was experienced.	12 weeks
Intervention fidelity	Physician-reported, two questions on use of recommendations in the dosing report.	12 weeks
Blinding fidelity	Physician-reported, 1-item survey about the perceived allocation of each of their participating patients; response options are 'PGx-guided prescribing', 'don't know' or 'current prescribing guidelines/recommendations'	12 weeks

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Amanda Newton, PhD, University of Alberta; Principal Investigator: Chad Bousman, PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pharmacogenetics; depression; anxiety; adolescence; SSRI; antidepressant
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Behavior; Anxiety Disorders; Depression
• Other Study ID Numbers: 2025-23-0532

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Anonymized, individual participant PGx-GAP data will be shared using a controlled-access model. Under this model, the data will be released to a researcher if access criteria are met.

All requests for data sharing should be made to the Co-Principal Investigators who will be responsible for reviewing and granting requests. Requestors should provide a research proposal for review. In the event that a data sharing request is declined, reasons will be provided to the requestor. If the data sharing request is granted, a data-sharing agreement will be initiated by the Co-Principal Investigators alongside the University of Calgary (lead institution). This agreement will include information on the individual data to be shared; if other documents will be available (e.g., statistical codes, data dictionary), when the data will be available and for how long, and how data access will be provided (e.g., file transfer).

• IPD Sharing Access Criteria: The requestor is affiliated with an academic institution as an independent investigator or trainee of an independent investigator;; The proposed research question(s) and hypothesis(es) are specific, measurable, and achievable;; The proposed research project will be governed/overseen by a local legal/regulatory body;; The proposed research project poses no risk of invasion of privacy or breaches of confidentiality for trial participants;; A member of the proposed research team has sufficient statistical skills to carry out the proposed analytic plan;; The requestor has sufficient financial and/or human resources to see the proposed research project to completion;; The proposed research question(s) and hypothesis(es) do not conflict with active or planned studies of the Co-Principal Investigators.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No