Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents With Anxiety and Depression

Not Applicable

Recruiting

• Conditions: Anxiety and Depression

• Registration Number: NCT06853587
• Lead Sponsor: University of Calgary

Brief Summary

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).

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 Timeline

• Status Verified: 2025-02
• Study Start: 2025-02-11
• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-02-26
• Study First Posted: 2025-03-03
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-27
• Primary Completion: 2027-09
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 452

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of participants with depression remission	Baseline to 12 weeks	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.
Number of participants with anxiety remission	Baseline to 12 weeks	Screen for Child Anxiety Related Disorders (SCARED) total score \< 25. Scores range from 0-82, with higher scores indicative of more severe anxiety.

Secondary Outcome Measures

Name	Time	Method
Number of participants with side effects and adverse drug reactions	Baseline to 12 weeks	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.
Percent change in role functioning	Baseline to 12 weeks	WHO Disability Assessment Schedule. Scores range from 0 to 48, with higher scores indicative of worse role functioning.
Percent change in depressive symptom severity	Baseline to 12 weeks	Quick Inventory of Depressive Symptomatology - Adolescent - 17-item (QIDS-A17). Scores range from 0-27, with higher scores indicative of more severe depression.
Percent change in anxiety symptom severity	Baseline to 12 weeks	Screen for Child Anxiety Related Disorders (SCARED) total score \< 25. Scores range from 0-82, with higher scores indicative of more severe anxiety.
Percent change in clinician assessment of depressive and anxiety symptom severity	Baseline to 12 weeks	Change in Clinical Global Impression Severity (CGI-S) scale. Scores range from 0-7, with higher scores indicative of more severe illness.
Change in self-report health care resource use	Baseline to 12 weeks	Resource use questionnaire that captures number of visits and out-of-pocket costs for various mental health services.
Change in healthcare utilization - physician visits	Baseline to 12 weeks	Administrative data will be obtained on change in number of physician visits.
Change in health care utilization - emergency department visits	Baseline to 12 weeks	Administrative data will be obtained on change in number of emergency department visits.
Change in health care utilization - hospitalizations	Baseline to 12 weeks	Administrative data will be obtained on change in number of hospitalizations.
Change in prescribed medication dose	Baseline to 12 weeks	Administrative data will be obtained on changes to prescribed medication doses.
Change in prescribed agent	Baseline to 12 weeks	Administrative data will be obtained on changes of agent for prescribed medications.
Change in prescribed medication duration	Baseline to 12 weeks	Administrative data will be obtained on duration of use of prescribed medications.
Change in health-related quality of life	Baseline to 12 weeks	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.
Change in medication adherence	4 to 12 weeks	Medication Adherence Report Scale (MARS-5) scores. Scores range from 5-25 with higher scores indicative of better medication adherence.
Change in behavioral activation	Baseline to 12 weeks	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.

Trial Locations

Locations (1)

University of Calgary; 🇨🇦 Calgary, Alberta, Canada