Attention deficit hyperactivity disorder (ADHD) is a mental health disorder characterized by hyperactive and impulsive behaviors. Treatments include cognitive behavioral therapy and prescription drugs (e.g., Ritalin). Antipsychotic drugs are not approved for use among children with behavioral problems such as ADHD. However, antipsychotic drugs are increasingly being prescribed to children with such conditions despite limited evidence available regarding their safety when used in this setting. Recently, safety concerns have emerged regarding possible harmful effects, including potential increased risks of metabolic disease (obesity), diabetes, cardiac arrhythmias (abnormal heart rhythms), and cardiac death (dying due to heart problems).
The safety of antipsychotic drugs among children with ADHD has only been examined in a limited number of studies conducted in real-world settings. These studies examined the risks of weight gain, diabetes, and death among children prescribed antipsychotic drugs for ADHD. However, these studies had important methodological flaws. In addition, antipsychotic drugs for ADHD are typically used at much lower doses than for other conditions and in conjunction with approved ADHD drugs. High-quality studies that use real-world data are needed to evaluate the safety of antipsychotic drugs among children with ADHD. To address this knowledge gap, we will use data from the Clinical Practice Research Datalink to compare the risks of overweight or obesity, diabetes, high cholesterol levels, and heart problems among children with ADHD prescribed antipsychotics versus approved ADHD drugs. This study will provide regulatory agencies with important information on the safety of “off-label” use antipsychotic drugs in this vulnerable population.
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.
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
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Christel Renoux - Collaborator - McGill University
Claire Lefebvre - Collaborator - University Of Montreal
Julia Brillinger - Collaborator - McGill University
Mélanie Henderson - Collaborator - University Of Montreal
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Reem Masarwa - Collaborator - PPD North America
Robert Platt - Collaborator - McGill University
Reem Masarwa - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data