Overview
This is a parallel arm randomized (1:1) controlled trial. Adolescents aged 12-17 years (n=452) that did not respond or tolerate first-line fluoxetine therapy will be randomly allocated to receive 12-weeks of pharmacogenetic-guided antidepressant therapy (experimental intervention) or GLAD-PC guided prescribing (control intervention).
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 who have not responded or tolerated first-line fluoxetine therapy, have superior efficacy following 12-weeks of therapy with an alternative SSRI?
The Trial: This is a parallel arm randomized controlled trial. Adolescents aged 12-17 years (n=452) that did not respond or tolerate first-line fluoxetine therapy 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
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
- Prior failure of fluoxetine therapy due to inefficacy or intolerance
- 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 antidepressants (including fluoxetine, i.e. failure of fluoxetine and two other agents) as confirmed by the treating physician
- Psychotherapy or brain stimulation-based therapy initiated within 8 weeks of referral, or plans to initiate/change these therapies during study participation
- History of liver or hematopoietic cell transplant
- History of CYP2B6, CYP2C19, or CYP2D6 testing