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

University of Calgary

Status: Enrolling

Conditions: Anxiety and Depression

Treatments: Other: Current prescribing guidelines/recommendations; Other: Pharmacogenetic-guided dosing

Study type: Interventional

Funder types: Other

Identifiers

NCT06853587

2025-23-0532

Details and patient eligibility

About

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).

Full 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.

Enrollment: 452 estimated patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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452 participants in 2 patient groups

Experimental: Pharmacogenetic (PGx)-Guided

Experimental group

Description:

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.

Treatment:

Other: Pharmacogenetic-guided dosing

Current Prescribing Guidelines/Recommendations

Active Comparator group

Description:

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.

Treatment:

Other: Current prescribing guidelines/recommendations