OU College of Medicine Researchers Part of National Study Comparing Two Different Medications for ADHD in Preschool-Age Children

In the largest analysis of its kind to date, University of Oklahoma College of Medicine researchers were part of a multisite study that compared the effectiveness and side effects of two different types of medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in preschool-age children. The results, which found comparable effectiveness between the two medications, will guide further studies in an age group that is experiencing a rise in ADHD diagnoses.

“This study is important because the diagnosis of ADHD in preschool-age children is now at 2%, which is higher than it has been in the past. Children with ADHD are more likely to be expelled from preschool, and academic under-achievement is more common,” said Ami Bax, M.D., who led the study for the OU College of Medicine and serves as Section Chief for Developmental and Behavioral Pediatrics in the Department of Pediatrics.

OU College of Medicine researchers participated in the study along with six other sites across the United States as part of the Developmental Behavioral Pediatrics Research Network (DBPNet). Collectively, they analyzed the outcomes of 500 preschool-age children who had been prescribed either a stimulant medication or an alpha-2 adrenergic agonist (A2A) medication to treat symptoms of ADHD. The medications were prescribed between 2013 and 2017; about one-third of the study population was prescribed an A2A medication and the rest received a stimulant medication. Stimulant medications for ADHD have been well-studied, are effective, and are more commonly prescribed, Bax said, but less is known about how well A2A medications work, particularly among preschool-age children.

The study found that both types of medications were effective for treating ADHD. The stimulants were slightly more effective than the A2A medications, Bax said, but the stimulants also had a few more side effects, including irritability, appetite suppression, headaches and stomach aches. A2A medications had a smaller amount of side effects, primarily daytime sleepiness.

The difference between the two medications is what they target in the brain – stimulants work on dopamine receptors and A2A medications work on alpha 2 receptors. Although stimulants are considered controlled substances because they run the risk of addiction in older, primarily adult, populations, they are actually the most well-studied class of medications in all of pediatrics, Bax said. However, until this study, researchers understood less about how well A2A medications worked as compared to stimulants in preschool-age children.

“Stimulants, when used appropriately, are safe and effective,” Bax said. “But this study was the first time that A2A medications had been analyzed in a large group of preschool-age children. The takeaway from the study is that both types of medications were effective in treating ADHD, with stimulants being slightly more effective but having more side effects. Depending on the severity of ADHD in children and how well they respond to different medications, we now really have two options that have some research to back them.”

When ADHD is diagnosed in preschool-age children, the first line of treatment is typically behavior therapy to guide parents in interactions with their children, an approach that is quite effective, Bax said. The study showed that only 45% of children received behavior therapy prior to medication, which may point to the shortage of behavioral therapists, particularly in rural states like Oklahoma. Bax and her study colleagues advocate for and highly recommend parent behavioral management therapy as the first-line treatment for preschool-age children with ADHD, but the study’s primary focus was the two types of medications, which physicians may prescribe when children need additional support.

The study was published in the Journal of the American Medical Association (JAMA). Bax said the next step for the Developmental Behavioral Pediatrics Research Network (DBPNet) is to further verify the data by creating a prospective randomized clinical trial in which preschool-age children are enrolled and assigned to receive one of the two medications.

Using the same data set, researchers published a related study that demonstrated telephone visits are just as effective as in-person visits to manage ADHD medications in preschoolers. While most diagnoses and medication prescriptions for ADHD were made during an in-person clinic visit, adjustments to the medications were often accomplished over the phone, Bax said. The data used in the study occurred before the onset of the COVID-19 pandemic, which makes the results even more relevant today.

“Telephone management is important because if we have wait until the next in-person visit to adjust medications, it would slow our progress toward reaching the right dosage,” Bax said. “During the pandemic, we have relied even more on telephone and virtual visits, so this study shows us that with frequent, close communication, we can get to the right medicine and the right dose faster.”