ADHD in Preschool Kids: Adrenergic Agonists May Be a Better Fit

A new study finds that α2-adrenergic agonists may be of benefit and have fewer side effects than stimulant medications for the treatment of attention deficit/hyperactivity disorder (ADHD) in preschool-age children.

The study was published online May 4 in JAMA.

As part of a retrospective analysis, Elizabeth Harstad, MD, MPH, from Boston Children’s Hospital, Boston, Massachusetts, and colleagues evaluated health record data from 497 preschool-age children with ADHD across seven developmental-behavioral pediatric practices in the United States. Children included in the evaluation were younger than 6 years and were treated for ADHD between January 1, 2013, and July 1, 2017, with either an α2-adrenergic agonist or a stimulant.

Overall, 175 children (35%) were prescribed an α2-adrenergic agonist (most often guanfacine) as first-line ADHD medication, and 322 children (65%) were prescribed a stimulant (most often a methylphenidate-based preparation). Before any medication regimens were initiated, 62% of children received behavioral therapy.

“These findings suggest that for some children, there may be a concern about either how well a stimulant will work or how well a stimulant will be tolerated that is leading clinicians to instead prescribe an α2-adrenergic agonist as the first medication tried,” Harstad told Medscape Medical News.

Clinical improvement was noted in 66% of children treated with α2-adrenergic agonists (95% CI, 57.5% to 73.9%) and in 78% of children treated with stimulants (95% CI, 72.4% to 83.4%).

Most adverse effects were more common among children who received stimulants than among those who received α2-adrenergic agonists. These adverse effects included difficulty falling asleep (21% vs 11%), decreased appetite (38% vs 7%), increased stomachaches (13% vs 5%), and increased skin picking/repetitive behaviors (11% vs 5%). Only daytime sleepiness was more frequent among children who received an α2-adrenergic agonist rather than a stimulant (38% vs 3%).

“We also found that for the youngest children (<4 years old), those initiated on α2-adrenergic agonists stayed on these medications longer than those initiated on stimulants, which may indicate that they are better tolerated, although more research is needed to confirm this,” Harstad said.

“While our study focused on how well medications work and how well they are tolerated when used to treat preschool-age children with ADHD, it is important to remember that behavioral therapy is recommended as first-line treatment for ADHD in preschool-age children, not medication,” Harstad added.

Mark Wolraich, MD, FAAP, from the University of Oklahoma, Oklahoma City, Oklahoma, echoed that sentiment. “The article mentions that behavioral interventions, in the form of parent training in behavior management, is an effective first-line treatment” and, per the American Academy of Pediatrics (AAP) guidelines, “is the first line of treatment recommended for preschool-age children before medication should be considered.”

Wolraich also notes that “neither drug has official FDA [US Food and Drug Administration] approval in this age group” but that “methylphenidate comes the closest to having met the FDA requirements for approval in this age group, which is why the AAP guidelines recommended its use if parent training in behavior management is not sufficient.”

Although Harstad and colleagues note that the study included a large and diverse sample size from across the United States, they acknowledge that “further research, including from randomized clinical trials, is needed to assess comparative effectiveness of α2-adrenergic agonists vs stimulants.”

Funding for the study was provided through a cooperative agreement with the Maternal and Child Health Bureau, the Health Resources and Services Administration, and the US Department of Health and Human Services. Harstad has reported receiving reported receiving compensation for serving as a medical reviewer for and grant funding from the Palmer Family Fund for Autism Research to conduct research related to autism spectrum disorder at Boston Children’s Hospital. Disclosures for the other authors are listed in the original article. Wolraich has disclosed no relevant financial relationships.

JAMA. Published online May 4, 2021. Full text

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