This is a parallel arm randomized (1:1) controlled trial. Adolescents aged 12-17 years (n=228) 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).
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=228) 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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
228
SSRI dosing based on Clinical Pharmacogenetics Implementation Consortium's SSRI dosing guidelines.
SSRI dosing based on current prescribing guidelines/recommendations
University of Calgary
Calgary, Alberta, Canada
RECRUITINGNumber 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.
Time frame: 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.
Time frame: Baseline to 12 weeks
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to 12 weeks
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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.
Time frame: 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.
Time frame: Baseline to 12 weeks
Change in healthcare utilization - physician visits
Administrative data will be obtained on change in number of physician visits.
Time frame: 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.
Time frame: Baseline to 12 weeks
Change in health care utilization - hospitalizations
Administrative data will be obtained on change in number of hospitalizations.
Time frame: Baseline to 12 weeks
Change in prescribed medication dose
Administrative data will be obtained on changes to prescribed medication doses.
Time frame: Baseline to 12 weeks
Change in prescribed agent
Administrative data will be obtained on changes of agent for prescribed medications.
Time frame: Baseline to 12 weeks
Change in prescribed medication duration
Administrative data will be obtained on duration of use of prescribed medications.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to 12 weeks