Anxiety and Depression
Conditions
Keywords
depression, anxiety, adolescence, SSRI, antidepressant, pharmacogenetics
Brief summary
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).
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=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.
Interventions
SSRI dosing based on Clinical Pharmacogenetics Implementation Consortium's SSRI dosing guidelines.
OTHERCurrent prescribing guidelines/recommendations
SSRI dosing based on current prescribing guidelines/recommendations
Sponsors
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, their prescribing physician, and the investigator will all be blinded to study arm. The study coordinator will be the only one unblinded to study arm allocation.
Intervention model description
This is a parallel arm randomized controlled trial.
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada
Contacts
CONTACTMadison Heintz, MSW
PRINCIPAL_INVESTIGATORChad Bousman, PhD
University of Calgary
PRINCIPAL_INVESTIGATORAmanda Newton, PhD
University of Alberta
Outcome results
None listed