PGx-AID: Pharmacogenetics of Antidepressant-Induced Disinhibition

Sponsor

University of Calgary (Other)

Overall Status

Recruiting

CT.gov ID

NCT03953014

Collaborator

Mathison Centre for Mental Health Education and Research (Other), Alberta Health services (Other)

120

Enrollment

Location

43.9

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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 Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Other

Time Perspective:

Cross-Sectional

Official Title:

Pharmacogenetics of Antidepressant-Induced Disinhibition in Children Study

Actual Study Start Date :

Jan 2, 2019

Anticipated Primary Completion Date :

Aug 31, 2022

Anticipated Study Completion Date :

Aug 31, 2022

Outcome Measures

Primary Outcome Measures

Genetic variants in SSRI metabolism [4 years]
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.
Behavioural Disinhibition [4 years]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 6 - 17 years
Medical records available
Diagnosis of MDD, anxiety disorder, or OCD
Current or past history of SSRI therapy

Exclusion Criteria:

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