1. In a retrospective cohort study, the use of alpha-2-adrenergic agonists to treat attention-deficit hyperactivity disorder (ADHD) in preschool children was associated with daytime sleepiness, moodiness/irritability, disruptive behavior, and difficulty sleeping.

2. Disruptive behavior was most common in children < 48 months of age. 

Evidence Rating Level: 2 (Good)

Study Rundown: Attention-Deficit/Hyperactivity Disorder (ADHD) in preschool children is commonly managed with stimulant medications and alpha-2-adrenergic agonists (A2A). While the side effects of A2A in general are known, they have not yet been well-described in preschool-aged children treated for ADHD. To address this shortcoming, authors performed a retrospective cohort study of 497 subjects to further characterize AEs associated with A2As compared to stimulant medications. Side effect profiles differed between medication classes, aside from a similar rate of disruptive behavior in both classes. Also, there was generally a higher frequency of side effects with stimulant use compared to A2A. Notably, A2A were commonly associated with daytime sleepiness, moodiness/irritability, disruptive behavior, and difficulty with sleep. In both drug classes, disruptive behavior was more common in younger age children and had the highest rates in children < 48 months of age. A major limitation of this study is the retrospective design, which may not accurately capture adverse events if they were not routinely assessed at follow-up. In general, this study provides evidence that A2A used in preschool children to treat ADHD are associated with a lower rate of side effects compared to stimulants.

Click here to read the article in Journal of Pediatrics

Relevant Reading: Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents

In-Depth [retrospective cohort]: This was a retrospective study across 7 academic medical centers in the United States within the Developmental-Behavioral Pediatrics Research Network (DBPNet). Participants included children <72 months of age, diagnosed with ADHD by a developmental pediatrician and treated with an A2A or stimulant medication between Jan 2013 and July 2017. Primary outcomes included commonly reported AEs: moodiness/irritability, appetite suppression, disruptive behavior, difficulty with sleep, daytime sleepiness, stomach aches, skin picking or other repetitive behaviors, headaches, withdrawn behavior, weight loss, dizziness, syncope, and other rare AEs captured by free text option. There were 497 participants included in the study, 65% (n=322) who received stimulant medications and 35% (n=175) who received immediate-release A2A. Commonly reported AEs for A2A were included daytime sleepiness (39%), moodiness/irritability (30%), disruptive behavior (28%), and difficulty with sleep (12.8%). Common side effects of stimulants included moodiness/irritability (51.6%), appetite suppression (35.6%), difficulties with sleep (23.7%), and disruptive behavior (26.1%). Logistic regression found that there were differences in all common AEs between medication classes, aside from disruptive behavior which is similar for A2A and stimulants. The only adverse effects that were modified by age were disruptive behavior (p=0.007) for both medication classes and difficulty sleeping (p=0.032) for stimulants, with younger children (<48 months of age) being disproportionally affected.

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