Study analyzes two different classes of drugs in a large group of preschoolers with ADHD

Reviewed by Emily Henderson, B.Sc.May 5 2021

In a multi-institutional study, researchers in the Developmental-Behavioral Pediatrics Research Network (DBPNet), led by Children's Hospital of Philadelphia (CHOP), have conducted the first and largest analysis to date comparing the effectiveness and side effects of stimulants like methylphenidate (Ritalin) and alpha-adrenergic agonists like guanfacine (Tenex) in preschool-age children. The researchers found that both classes of drugs have benefits, with differing side effects, suggesting that decisions on which class of drugs to prescribe should be made based on individual patient factors. The retrospective study was published today in JAMA.

This is really the first study of any size to report on the frequency of improvement and side effects of drugs like guanfacine in preschool-age children. While this study confirms that clinicians are using drugs like guanfacine in preschoolers and that those drugs may be useful in some children, the research also strongly suggests we need future research to look in a rigorous way at the use of alpha-adrenergic agonists in this age group."

Nathan J. Blum, MD, Senior Author, Chief of the Division of Developmental and Behavioral Pediatrics at CHOP

To assess the use, effectiveness, and side effects of stimulants and alpha-adrenergic agonists in preschoolers, the researchers reviewed electronic health records of 497 children seen at seven DBPNet outpatient developmental-behavioral pediatric practices between January 2013 and July 2017. Children included in the study were under the age of 6 when first treated with an alpha-adrenergic agonist or stimulant.

The researchers found that 175 children (35%) were prescribed an alpha-adrenergic agonist like guanfacine, while 322 children (65%) were prescribed a stimulant like methylphenidate (Ritalin). Although both groups reported improvement in symptoms, the benefit was slightly larger among those prescribed stimulants (78% vs. 66%).

However, in terms of side effects, patients taking alpha-adrenergic agonists reported fewer side effects than those taking stimulants, with lower rates of moodiness/irritability (50% vs. 29%), appetite suppression (38% vs. 7%), and difficulty sleeping (21% vs. 11%). The only side effect that was more common for those taking alpha-adrenergic agonists than those taking stimulants was daytime sleepiness (38% vs. 3%).

The researchers also found children younger than 4 years old who were prescribed a drug like guanfacine were likely to continue using the medication for longer than if they were prescribed a stimulant. In contrast, children aged 5 to younger than 6 prescribed were likely to continue using the medication for longer if they were prescribed a stimulant. For those ages 4 to 5, there was no significant difference between medications.

"Although the retrospective nature of our study means we weren't able to tell why patients stopped a given medication rather than continued with it, these data support potentially tailoring medication based on a child's age, among other personal factors that might influence medication decisions," Blum said. "Future research should seek to learn more about the use of these classes of drugs in preschool-age children so that we can prescribe the most effective therapy for each patient.