Pharmacogenetics of Antidepressant-Induced Disinhibition

Major Depressive Disorder Clinical Trial

— PGx-AID  

Official title:

Pharmacogenetics of Antidepressant-Induced Disinhibition in Children Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03953014
• Other study ID #: REB18-0519
• Status: Recruiting
• Start date: January 2, 2019
• Est. completion date: June 30, 2025

Study information

• Verified date: May 2022
• Source: University of Calgary
• Contact: Madison Heintz, MSW
• Phone: 5875739747
• Email: psychpgxlab[@]ucalgary.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Antidepressant Drug Adverse Reaction
• Anxiety Disorders
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Drug-Related Side Effects and Adverse Reactions
• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Locations

Country	Name	City	State
Canada	Child and Adolescent Addiction, Mental Health & Psychiatry	Calgary	Alberta

Sponsors (3)

Lead Sponsor	Collaborator
University of Calgary	Alberta Health services, Hotchkiss Brain Institute, University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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