Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents

Depression in Adolescence Clinical Trial

— PGx-GAP  

Official title:

Pharmacogenetic-Guided Antidepressant Prescribing (PGx-GAP) in Adolescents

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05965401
• Other study ID #: REB23-0532
• Status: Recruiting
• Phase: N/A
• Start date: October 25, 2023
• Est. completion date: December 2027

Study information

• Verified date: October 2023
• Source: University of Calgary
• Contact: Laina McAusland, MSc
• Phone: 403-210-6353
• Email: gap[@]ucalgary.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 452
• Est. completion date: December 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

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

Related Conditions & MeSH terms

• Depression
• Depression in Adolescence

Intervention

Other:
• Pharmacogenetic-guided dosing
SSRI dosing based on Clinical Pharmacogenetics Implementation Consortium's SSRI dosing guidelines.
• GLAD-PC guided dosing
SSRI dosing based on GLAD-PC clinical practice guidelines

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	University of Alberta

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimally clinically important differences	Participant-reported, Global Rating of Change Scale (GRCS) (11-point Likert scale ranging from +5 to -5) to indicate the degree to which symptoms and role functioning changed for the better, for the worse, or no change was experienced.	12 weeks
Other	Intervention fidelity	Physician-reported, two questions on use of recommendations in the dosing report.	12 weeks
Other	Blinding fidelity	Physician-reported, 1-item survey about the perceived allocation of each of their participating patients; response options are 'PGx-guided prescribing', 'don't know' or 'GLAD-PC prescribing'	12 weeks
Primary	Number 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.	Baseline to 12 weeks
Secondary	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.	Baseline to 12 weeks
Secondary	Percent Change in Role functioning	WHO Disability Assessment Schedule. Scores range from 0 to 48, with higher scores indicative of worse role functioning.	Baseline to 12 weeks
Secondary	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.	Baseline to 12 weeks
Secondary	Percent Change in clinician assessment of depressive symptom severity	Change in Clinical Global Impression Severity (CGI-S) scale. Scores range from 0-7, with higher scores indicative of more severe illness.	Baseline to 12 weeks
Secondary	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.	Baseline to 12 weeks
Secondary	Change in health care utilization	Administrative data will be obtained on medication information (agent, dose, duration) and health care utilization (doctor visits, hospitalizations, emergency room visits).	Baseline to 12 weeks
Secondary	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.	Baseline to 12 weeks
Secondary	Change in medication adherence	Medication Adherence Report Scale (MARS-5) scores. Scores range from 5-25 with higher scores indicative of better medication adherence.	4 to 12 weeks
Secondary	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.	Baseline to 12 weeks