Pharmacogenetics of Antidepressant-Induced Disinhibition (PGx-AID)

Pharmacogenetics of Antidepressant-Induced Disinhibition in Children Study

The purpose of this study is to identify pharmacogenetic profiles associated with selective serotonin reuptake inhibitors (SSRI)-induced behavioral disinhibition in children with Major depressive disorder (MDD), anxiety disorders and/or obsessive-compulsive disorder (OCD) that could be used clinically to reduce the incidence of this adverse event and improve health outcomes.

Study Overview

• Status: Recruiting
• Conditions: Obsessive-Compulsive Disorder; Anxiety Disorders; Major Depressive Disorder; Antidepressant Drug Adverse Reaction

Detailed Description

Background and Rationale:

Antidepressants such as serotonin-selective reuptake inhibitors (SSRIs) are frequently prescribed to children to manage major depressive and anxiety disorders. Although SSRIs are thought to be generally effective and well-tolerated in children, 10%- 20% of children treated with SSRIs experience behavioral disinhibition (i.e. activation, hyperactivity, impulsivity, insomnia) that can lead to devastating consequences (e.g. suicidal impulses, violence). There are currently no tools available to assist healthcare providers in predicting which children will experience behavioral disinhibition as a result of SSRI treatment.

Research Question:

Do children who experience SSRI-induced behavioral disinhibition (SIBD) have a distinct pharmacogenetic profile relative to children who do not have these adverse experiences?

Methodology:

Using a retrospective cohort study design, 120 SSRI-treated children diagnose with major depression, anxiety and OCD, aged 6 to 17 years of aged will be recruited from Child and Adolescent Addiction, Mental Health & Psychiatry (CAAMHP) Program in Calgary. Children with a current or past history of SSRI use will be identified via recruitment advertisements and by CAAMHP treatment teams operating within community clinics as well as inpatient units within the Alberta Children's Hospital and Foothills Medical Centre.

Clinical data will be collected from the participant's medical record as well as information provided by the child's healthcare provider and caretaker using a customized data collection form. Saliva will be collected, processed and genotyped in accordance with standard procedures. Participants and their parents will complete self-report measures to gather information regarding demographics, SIBD, and other adverse side effects and drug reactions.

Using machine learning (i.e. the construction of algorithms that can learn from and make predictions on data) we will identify and validate a panel of genetic variants that could be used to pre-emptively detect children at-risk for developing SSRI-induced behavioral disinhibition.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Madison Heintz, MSW; Phone Number: 5875739747; Email: psychpgxlab@ucalgary.ca
• Study Contact Backup: Name: Abdullah Al Maruf, PhD; Email: abdullahal.maruf@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Child and Adolescent Addiction, Mental Health & Psychiatry
      • Contact: Madison Heintz, MSW
      • Principal Investigator: Chad Bousman, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

SSRI-treated children diagnosed with major depression, anxiety and OCD, aged 6 to 24 years recruited from the Child and Adolescent Addiction, Mental Health & Psychiatry (CAAMP) Program in Calgary.

Description

Inclusion Criteria:

1. Aged 6 - 24 years
2. Medical records available
3. Diagnosis of MDD, anxiety disorder, or OCD
4. Current or past history of SSRI therapy

Exclusion Criteria:

1. Inability of parent/legal guardian to give informed consent
2. Inability of the child to give informed assent
3. Unwillingness of child to provide saliva sample for genetic analysis
4. Current, past or suspected diagnosis of attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, bipolar disorder, psychotic disorder, or pervasive developmental disorder.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variants in SSRI metabolism	DNA Sample Collection & Genotyping. Saliva will be collected using Oragene® collection tubes (DNA Genotek, Ottawa, Canada). DNA will be extracted using standard procedures and genotyped.	4 years
Behavioural Disinhibition	Information on behavioural disinhibition (BD) to note the type, duration and severity of BD gathered from medical records, and participant and parent report. The Treatment-emergent activation and suicidality assessment profile (TEASAP), is a questionnaire that assess common symptoms of activation syndrome/behavioural disinhibition in youth due to SSRI usage.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Drug Reactions other than SIBD	A self-report instrument, The Antidepressant Side-Effect Checklist (ASEC) will be used to assess the presence of common adverse reactions to antidepressants.	4 years

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Alberta Health services; Hotchkiss Brain Institute, University of Calgary
• Investigators: Principal Investigator: Paul Arnold, MD, University of Calgary

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 2, 2019
• Primary Completion (ANTICIPATED): June 30, 2025
• Study Completion (ANTICIPATED): June 30, 2025

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (ACTUAL): May 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 7, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Depression; OCD; Anxiety; Children; Antidepressants; SSRI
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Disease; Obsessive-Compulsive Disorder; Anxiety Disorders; Depressive Disorder, Major; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: REB18-0519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No