Clinical trial NCT05965401: Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents
Official title: Pharmacogenetic-Guided Antidepressant Prescribing (PGx-GAP) in Adolescents
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Depression in Adolescence
Keywords: Depression
Adolescence
SSRI
Antidepressant
Pharmacogenetics
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: University of Alberta
First posted: 2023-07-28
Enrollment: 11
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel arm randomized controlled trial.
Primary purpose: TREATMENT

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 will be randomly allocated to receive 12-weeks of pharmacogenetic-guided antidepressant therapy (experimental intervention) or GLAD-PC guided prescribing (control intervention).

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

Background: For an adolescent with moderate to severe depression, 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 (Guidelines for Adolescent Depression in Primary Care, GLAD-PC). However, GLAD-PC does 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 GLAD-PC informed prescribing, does pharmacogenetic-guided prescribing for depressed adolescents 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 will be randomly allocated to receive pharmacogenetic-guided antidepressant therapy (experimental intervention) or GLAD-PC 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). 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.

Eligibility criteria: Inclusion Criteria:

* Age 12-17
* Depression as the primary concern, confirmed by the treating physician
* QIDS-A17 score greater than or equal to 11 indicating moderate-to-severe symptoms
* Intention to start a new SSRI
* English fluency

Exclusion Criteria:

* Co-occurring psychosis, bipolar disorder, eating disorder, autism spectrum disorder, fetal alcohol spectrum disorder, or intellectual disability
* A score of 2 or 3 on suicide item 13 of the QIDS-A17
* High-risk alcohol or substance use (excluding cannabis and tobacco) as indicated by a score of monthly or more on the S2BI
* 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

Primary outcomes:
measure: Number of participants with depression remission
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Number of participants with side effects and adverse drug reactions
timeFrame: Baseline to 12 weeks
measure: Percent Change in Role functioning
timeFrame: Baseline to 12 weeks
measure: Percent Change in Depressive Symptom Severity
timeFrame: Baseline to 12 weeks
measure: Percent Change in clinician assessment of depressive symptom severity
timeFrame: Baseline to 12 weeks
measure: Change in self-report health care resource use
timeFrame: Baseline to 12 weeks
measure: Change in health care utilization
timeFrame: Baseline to 12 weeks
measure: Change in health-related quality of life
timeFrame: Baseline to 12 weeks
measure: Change in medication adherence
timeFrame: 4 to 12 weeks
measure: Change in behavioral activation
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: Minimally clinically important differences
timeFrame: 12 weeks
measure: Intervention fidelity
timeFrame: 12 weeks
measure: Blinding fidelity
timeFrame: 12 weeks
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Chad Bousman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Amanda Newton, PhD
role: PRINCIPAL_INVESTIGATOR
References: