The safety of antipsychotic drugs in children and youth with attention deficit and hyperactivity disorder

Date of Approval
Application Number
21_000549
Technical Summary

We will conduct a population-based cohort study including children and youth aged 5 to 24 years with an ADHD diagnosis between January 1st, 1998 and December 31st, 2020. Our primary objective is to compare the rates of a composite outcome of incident overweight/obesity in children and youth with ADHD exposed to antipsychotics to that among children and youth with ADHD prescribed approved ADHD drugs without antipsychotics. Our secondary objectives are to compare the risks of 1) incident type 2 diabetes; 2) incident dyslipidemia; 3) incident obesity and overweight as individual endpoints; 4) primary arrhythmias; 5) a composite endpoint of sudden cardiac death and ventricular tachyarrhythmia with use of antipsychotic drugs, compared to use of approved ADHD drugs only, among children and youth with ADHD; and 6) prescription rates approved ADHD drugs and antipsychotics among children and youth with ADHD.

To address these objectives, we will conduct a retrospective cohort study using a prevalent new user design. We will construct a base cohort of all children and youth aged 5 to 24 years with an ADHD diagnosis who received an indicated drug for ADHD (stimulants or non-stimulants) in the study period between January 1st, 1998 to December 31st, 2020. From this cohort, we will select our study cohort, which will include children and youth who received their first antipsychotic prescription (i.e., added to or switching from an approved ADHD drug) and matched comparators (those using approved ADHD drugs only). Individuals will be matched on age, sex, time since ADHD diagnosis, and time-conditional propensity score to minimize confounding. We will use Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for antipsychotics vs approved ADHD drugs for the outcomes of interest. Poisson regression will be used to calculate annual prescription rates of antipsychotics and approved ADHD drugs.

Health Outcomes to be Measured

1. A composite endpoint of incident obesity and overweight
2. Incident dyslipidaemia
3. Incident type 2 diabetes
4. Incident obesity and overweight as individual endpoints
5. Primary arrhythmias
6. A composite endpoint of sudden cardiac death (SCD) and ventricular tachycardia (VT)
7. Prescription rates of approved ADHD drugs antipsychotic drugs

Collaborators

Samy Suissa - Chief Investigator - McGill University
Kristian Filion - Corresponding Applicant - McGill University
Christel Renoux - Collaborator - McGill University
Claire Lefebvre - Collaborator - University Of Montreal
Mélanie Henderson - Collaborator - University Of Montreal
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Reem Masarwa - Collaborator - McGill University
Robert Platt - Collaborator - McGill University

Linkages

HES Admitted Patient Care;ONS Death Registration Data