Pharmacogenetics of Antidepressant-Induced Disinhibition

NCT ID: NCT03953014

Last Updated: 2024-05-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 120 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-02
• Study Completion Date: 2025-06-30

Brief Summary

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.

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.

Conditions

Obsessive-Compulsive Disorder; Anxiety Disorders; Major Depressive Disorder; Antidepressant Drug Adverse Reaction

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: CROSS_SECTIONAL

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hotchkiss Brain Institute, University of Calgary

OTHER

Sponsor Role: collaborator

Alberta Health services

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chad Bousman, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Paul Arnold, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Child and Adolescent Addiction, Mental Health & Psychiatry

Calgary, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Madison Heintz, MSW

Role: CONTACT

psychpgxlab@ucalgary.ca

5875739747

Abdullah Al Maruf, PhD

Role: CONTACT

abdullahal.maruf@ucalgary.ca

Facility Contacts

Madison Heintz, MSW

Role: primary

Other Identifiers

REB18-0519

Identifier Type: -

Identifier Source: org_study_id